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3. Rao VK, Dowdell KC, Dale JK, Dugan F, Pesnicak L, Bi LL, Hoffmann V, Penzak S, Avila NA, Fleisher TA, Puck JM, Straus SE: Pyrimethamine treatment does not ameliorate lymphoproliferation or autoimmune disease in MRL/lpr-/- mice or in patients with autoimmune lymphoproliferative syndrome. Am J Hematol; 2007 Dec;82(12):1049-55
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  • [Title] Pyrimethamine treatment does not ameliorate lymphoproliferation or autoimmune disease in MRL/lpr-/- mice or in patients with autoimmune lymphoproliferative syndrome.
  • Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder of lymphocyte apoptosis leading to childhood onset of marked lymphadenopathy, hepatosplenomegaly, autoimmune cytopenias, and increased risk of lymphoma.
  • Most cases are associated with heterozygous mutations in the gene encoding Fas protein.
  • Prolonged use of immunosuppressive drugs that do ameliorate its autoimmune complications fail to consistently lessen lymphoproliferation in ALPS.
  • A case series had described children with ALPS, whose spleens (SPL) and lymph nodes decreased in size when treated weekly with pyrimethamine and sulfadoxine; parallel in vitro studies showed only pyrimethamine to promote apoptosis.
  • Moreover, seven children with ALPS enrolled in a study of escalating dose of pyrimethamine alone given twice weekly for 12 weeks to determine if their lymphadenopathy and/or splenomegaly would diminish, as assessed by standardized computerized tomography.
  • Neither pyrimethamine alone or with sulfadoxine in the MRL/lpr-/- mice, nor pyrimethamine alone in ALPS patients proved efficacious.
  • We conclude that these drugs do not warrant further use empirically or as part of clinical trials in ALPS Type Ia as a lympholytic agent.
  • [MeSH-major] Autoimmune Diseases / drug therapy. Lymphoproliferative Disorders / drug therapy. Lymphoproliferative Disorders / immunology. Pyrimethamine / therapeutic use

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  • (PMID = 17674358.001).
  • [ISSN] 0361-8609
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Grant] United States / Intramural NIH HHS / /
  • [Publication-type] Journal Article; Research Support, N.I.H., Intramural
  • [Publication-country] United States
  • [Chemical-registry-number] Z3614QOX8W / Pyrimethamine
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4. Dowdell KC, Pesnicak L, Hoffmann V, Steadman K, Remaley AT, Cohen JI, Straus SE, Rao VK: Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, diminishes lymphoproliferation in the Fas -deficient MRL/lpr(-/-) murine model of autoimmune lymphoproliferative syndrome (ALPS). Exp Hematol; 2009 Apr;37(4):487-94
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  • [Title] Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, diminishes lymphoproliferation in the Fas -deficient MRL/lpr(-/-) murine model of autoimmune lymphoproliferative syndrome (ALPS).
  • OBJECTIVE: Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of apoptosis, often presenting in childhood.
  • Similarly, MRL/lpr(-/-) mice homozygous for Fas mutations develop an ALPS-like disease with autoimmunity, lymphadenopathy, splenomegaly, and expansion of double-negative T cells.
  • Currently, there are no proven therapies with adequate safety margins for sustained abolition of the lymphoproliferation associated with ALPS.
  • MATERIALS AND METHODS: Human peripheral blood mononuclear cells from patients with ALPS and normal controls were tested in vitro to determine the efficacy of VPA at inducing cell death.
  • VPA was used in vivo to control lymphoproliferation in MRL/lpr(-/-) mice, a model for ALPS.
  • CONCLUSION: Based on our data, VPA is effective at reducing lymphoproliferation in mice, and is currently being studied in a clinical trial as a lympholytic agent in patients with ALPS.
  • [MeSH-major] Apoptosis / drug effects. Autoimmune Diseases / drug therapy. Enzyme Inhibitors / pharmacology. Histone Deacetylase Inhibitors. Lymphoproliferative Disorders / drug therapy. T-Lymphocytes / drug effects. Valproic Acid / pharmacology
  • [MeSH-minor] Animals. Antigens, CD95 / genetics. Cell Proliferation / drug effects. Cells, Cultured. Disease Models, Animal. Female. Humans. Leukocytes, Mononuclear / cytology. Leukocytes, Mononuclear / drug effects. Leukocytes, Mononuclear / immunology. Mice. Mice, Knockout. Reference Standards. Syndrome


5. Rao VK, Carrasquillo JA, Dale JK, Bacharach SL, Whatley M, Dugan F, Tretler J, Fleisher T, Puck JM, Wilson W, Jaffe ES, Avila N, Chen CC, Straus SE: Fluorodeoxyglucose positron emission tomography (FDG-PET) for monitoring lymphadenopathy in the autoimmune lymphoproliferative syndrome (ALPS). Am J Hematol; 2006 Feb;81(2):81-5
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  • [Title] Fluorodeoxyglucose positron emission tomography (FDG-PET) for monitoring lymphadenopathy in the autoimmune lymphoproliferative syndrome (ALPS).
  • Autoimmune lymphoproliferative syndrome (ALPS) is associated with mutations that impair the activity of lymphocyte apoptosis proteins, leading to chronic lymphadenopathy, hepatosplenomegaly, autoimmunity, and an increased risk of lymphoma.
  • We investigated the utility of fluorodeoxyglucose positron emission tomography (FDG-PET) in discriminating benign from malignant lymphadenopathy in ALPS.
  • We report that FDG avidity of benign lymph nodes in ALPS can be high and, hence, by itself does not imply presence of lymphoma; but FDG-PET can help guide the decision for selecting which of many enlarged nodes in ALPS patients to biopsy when lymphoma is suspected.
  • [MeSH-major] Fluorodeoxyglucose F18. Lymphatic Diseases / diagnosis. Lymphoma / diagnosis. Lymphoproliferative Disorders / diagnosis. Positron-Emission Tomography / methods
  • [MeSH-minor] Autoimmune Diseases / diagnosis. Autoimmune Diseases / pathology. Biopsy. Diagnosis, Differential. Female. Humans. Lymph Nodes / pathology. Male. Mutation. Prospective Studies

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  • [Copyright] 2006 Wiley-Liss, Inc.
  • [ErratumIn] Am J Hematol. 2006 May;81(5):389
  • (PMID = 16432855.001).
  • [ISSN] 0361-8609
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Grant] United States / Intramural NIH HHS / /
  • [Publication-type] Case Reports; Clinical Trial; Journal Article; Research Support, N.I.H., Intramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0Z5B2CJX4D / Fluorodeoxyglucose F18
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6. Liu X, Karnell JL, Yin B, Zhang R, Zhang J, Li P, Choi Y, Maltzman JS, Pear WS, Bassing CH, Turka LA: Distinct roles for PTEN in prevention of T cell lymphoma and autoimmunity in mice. J Clin Invest; 2010 Jul;120(7):2497-507
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  • [Title] Distinct roles for PTEN in prevention of T cell lymphoma and autoimmunity in mice.
  • Mutations in the tumor-suppressor gene phosphatase and tensin homolog deleted on chromosome 10 (Pten) are associated with multiple cancers in humans, including T cell malignancies.
  • Targeted deletion of Pten in T cells induces both a disseminated "mature phenotype" lymphoma and a lymphoproliferative autoimmune syndrome in mice.
  • These data suggest multiple and distinct regulatory roles for PTEN in the molecular pathogenesis of lymphoma and autoimmunity.

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  • (PMID = 20516645.001).
  • [ISSN] 1558-8238
  • [Journal-full-title] The Journal of clinical investigation
  • [ISO-abbreviation] J. Clin. Invest.
  • [Language] ENG
  • [Grant] United States / NIAID NIH HHS / AI / R01 AI047833; United States / NIAID NIH HHS / AI / AI047833; United States / NCI NIH HHS / CA / R01 CA125195; United States / NIAID NIH HHS / AI / AI 43620; United States / NCI NIH HHS / CA / CA119070; United States / NIAID NIH HHS / AI / P01 AI043620; United States / NCI NIH HHS / CA / CA125195; United States / NCI NIH HHS / CA / P01 CA119070
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Receptors, Antigen, T-Cell, alpha-beta; EC 3.1.3.- / Phosphoric Monoester Hydrolases; EC 3.1.3.48 / PTEN protein, human; EC 3.1.3.67 / PTEN Phosphohydrolase
  • [Other-IDs] NLM/ PMC2898609
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7. Prochorec-Sobieszek M, Wagner T: [Lymphoproliferative disorders in Sjögren's syndrome]. Otolaryngol Pol; 2005;59(4):559-64
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  • [Title] [Lymphoproliferative disorders in Sjögren's syndrome].
  • INTRODUCTION: Sjögren's syndrome [SS] is an autoimmune disease that mainly affects the exocrine glands.
  • B-cell lymphoproliferation is a characteristic feature of this syndrome and the lesion may range from benign to malignant.
  • RESULTS: Patients with Sjögren's syndrome [SS] have over 40-fold increased risk of the development B-cell non-Hodgkin's lymphoma.
  • Most cases of lymphomas complicating the course of SS arise in mucosal extranodal sites, especially in the salivary gland, and are classified as low grade marginal zone B-cell lymphoma with long-term survival.
  • The main problem in salivary lymphoproliferation in Sjögren's syndrome consists in the difficulties in the differential diagnosis of lymphoma.
  • Genotypic studies have documented the rearrangement of immunoglobulin genes across the full spectrum of lymphoid infiltrates in the salivary gland including cases regarded as reactive lymphoepithelial sialadenitis [LESA], borderline cases with halos of monocytoid cells surrounding epimyoepithelial islets, and cases with fully developed marginal zone lymphoma [MZL].
  • The pathophysiology of lymphoma in SS remains still unknown.
  • Viral infection, hyperstimulation of B cells, disregulation in the process of apoptosis, and unknown oncogenes are suspected to initiate the start of lymphoma.
  • The main clinical features associated with the development of lymphoma in SS include persistent major salivary gland enlargement (> 2 months), persistent lymphadenopathy or splenomegaly, monoclonal gammapathy and type II mixed cryoglobulinemia.
  • The treatment and prognosis of lymphoma associated with SS depend on the type and stage of lymphoma.
  • CONCLUSION: Patients with SS develop a variety B lymphoproliferative disorders.
  • [MeSH-major] Lymphoma, B-Cell / diagnosis. Lymphoma, B-Cell / etiology. Salivary Gland Neoplasms / etiology. Sjogren's Syndrome / complications

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  • (PMID = 16273862.001).
  • [ISSN] 0030-6657
  • [Journal-full-title] Otolaryngologia polska = The Polish otolaryngology
  • [ISO-abbreviation] Otolaryngol Pol
  • [Language] pol
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Poland
  • [Chemical-registry-number] 0 / Antigens, CD20
  • [Number-of-references] 25
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8. Bryce AH, Dispenzieri A, Kyle RA, Lacy MQ, Rajkumar SV, Inwards DJ, Yasenchak CA, Kumar SK, Gertz MA: Response to rituximab in patients with type II cryoglobulinemia. Clin Lymphoma Myeloma; 2006 Sep;7(2):140-4
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  • Type II cryoglobulinemia (CG) is a heterogeneous, generally indolent disorder caused by a monoclonal antibody with activity against polyclonal antibodies and is commonly associated with hepatitis C, lymphoproliferative disorders (LPDs), or autoimmune diseases.
  • Six patients had an LPD, and 4 of them had concomitant disorders (2 with hepatitis C and 2 with Sjogren syndrome).
  • Cutaneous manifestations were the most responsive; renal disease and lymphoma were more refractory.

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  • (PMID = 17026826.001).
  • [ISSN] 1557-9190
  • [Journal-full-title] Clinical lymphoma & myeloma
  • [ISO-abbreviation] Clin Lymphoma Myeloma
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA-62242
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Blood Proteins; 0 / Immunologic Factors; 4F4X42SYQ6 / Rituximab
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9. Grulich AE, Vajdic CM: The epidemiology of non-Hodgkin lymphoma. Pathology; 2005 Dec;37(6):409-19
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  • [Title] The epidemiology of non-Hodgkin lymphoma.
  • Non-Hodgkin lymphoma (NHL) includes a group of more than 20 different malignant lymphoproliferative diseases that originate from lymphocytes.
  • The best described risk factor for NHL is immune deficiency; rates of NHL are greatly increased, with relative risks of 10-100 or more, in people with immune deficiency associated with immune suppressive therapy after transplantation, HIV/AIDS, and congenital conditions.
  • In addition, some NHL subtypes are associated with specific infections.
  • These include immune-deficiency-associated central nervous system NHL (Epstein-Barr virus); gastric mucosa-associated lymphoid tissue NHL (Helicobacter pylori); adult T-cell leukemia/lymphoma (human T-lymphotrophic virus type 1) and body cavity-based lymphoma (human herpesvirus 8).
  • Specific autoimmune conditions, including rheumatoid arthritis, systemic lupus erythema, Sjogren's syndrome, psoriasis and coeliac disease are associated with moderately increased risk of NHL.
  • On the other hand, allergic and atopic conditions and their correlates such as early birth order, appear to be associated with a decreased risk of NHL.A variety of other exposures are less strongly related to NHL risk.
  • Recently, two studies have reported that sun exposure is associated with a decreased risk of NHL.
  • Smoking appears to be weakly positively associated with risk of follicular NHL, and alcohol intake is associated with a decreased risk of NHL.
  • [MeSH-major] Lymphoma, Non-Hodgkin / epidemiology


10. Yeh S, Li Z, Sen HN, Lim WK, Gill F, Perkins K, Rao VK, Nussenblatt RB: Scleritis and multiple systemic autoimmune manifestations in chronic natural killer cell lymphocytosis associated with elevated TCRalpha/beta+CD3+CD4-CD8- double-negative T cells. Br J Ophthalmol; 2010 Jun;94(6):748-52
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  • [Title] Scleritis and multiple systemic autoimmune manifestations in chronic natural killer cell lymphocytosis associated with elevated TCRalpha/beta+CD3+CD4-CD8- double-negative T cells.
  • BACKGROUND/AIMS: Chronic natural killer lymphocytosis (CNKL) has been associated with systemic autoimmunity; however, its association with scleritis or ocular autoimmunity has not been characterised.
  • The natural killer (NK) cell function and immunophenotype of a patient with CNKL who developed bilateral scleritis and multiple systemic autoimmune findings were evaluated.
  • RESULTS: A 56-year-old woman with vitiligo, psoriatic arthritis, thyroiditis, erythema nodosum, bilateral anterior scleritis and Sjogren syndrome was managed with multiple immunosuppressive medications, including prednisone, mycophenolate mofetil and methotrexate.
  • An abnormal elevation of TCRalpha/beta(+) CD3(+)CD4(-)CD8(-) T cells suggestive of autoimmune lymphoproliferative syndrome was observed; however, apoptosis dysfunction was not found.
  • [MeSH-major] Autoimmune Diseases / immunology. Killer Cells, Natural / immunology. Lymphocytosis / immunology. Scleritis / immunology. T-Lymphocyte Subsets / immunology

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  • (PMID = 20508050.001).
  • [ISSN] 1468-2079
  • [Journal-full-title] The British journal of ophthalmology
  • [ISO-abbreviation] Br J Ophthalmol
  • [Language] eng
  • [Grant] United States / Intramural NIH HHS / / Z01 EY000393-06; United States / Intramural NIH HHS / / ZIA EY000376-09
  • [Publication-type] Case Reports; Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Cytokines; 0 / Interleukin-2; 0 / Receptors, Antigen, T-Cell, alpha-beta
  • [Other-IDs] NLM/ NIHMS320628; NLM/ PMC3172679
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11. De Re V, Caggiari L, Simula MP, De Vita S, Mazzaro C, Lenzi M, Massimo GM, Monti G, Ferri C, Zignego AL, Gabrielli A, Sansonno D, Dammacco F, Libra M, Sacchi N, Talamini R, Spina M, Tirelli U, Cannizzaro R, Dolcetti R: Role of the HLA class II: HCV-related disorders. Ann N Y Acad Sci; 2007 Jun;1107:308-18
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  • The paper highlights the role of different HLA class II molecules in hepatic and lymphoproliferative HCV-related disorders.
  • Thus, by reducing the complexity of HLA II polymorphism, characteristics that unite different HLA molecules with specific HCV-associated pathologies may be recognized with greater case.
  • Results show that HLA clusters associated with better dlimination of the virus are protective against HCC development, while the same clusters are associated with a higher risk of developing cryoglobulinemic syndrome and the concomitant NHL.
  • These data added further acknowledgements on pathogenetic mechanisms associated with HCV infection.
  • Results also highlight differences of NHL occurring in HCV-positive subjects, with or without a concomitant type II autoimmune cryoglobulinemic syndrome, suggesting that cryoglobulinemic background associated with NHL should be considered in the evaluation of the effectiveness of new therapies in the course of HCV-associated NHLs.
  • [MeSH-minor] Autoimmune Diseases / immunology. Autoimmune Diseases / pathology. Cryoglobulinemia / immunology. Cryoglobulinemia / pathology. Fibrosis / immunology. Fibrosis / pathology. Fibrosis / virology. Hepacivirus / immunology. Hepacivirus / pathogenicity. Humans. Liver Neoplasms / immunology. Liver Neoplasms / pathology. Liver Neoplasms / virology. Lymphoma, B-Cell / immunology. Lymphoma, B-Cell / pathology. T-Lymphocytes, Helper-Inducer / immunology

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  • (PMID = 17804559.001).
  • [ISSN] 0077-8923
  • [Journal-full-title] Annals of the New York Academy of Sciences
  • [ISO-abbreviation] Ann. N. Y. Acad. Sci.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Histocompatibility Antigens Class II
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12. Mascia MT, Ferrari D, Campioli D, Sandri G, Mussini C, Ferri C: Non HCV-related mixed cryoglobulinemia. Dig Liver Dis; 2007 Sep;39 Suppl 1:S61-4
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  • Interestingly, patients with Sjögren's syndrome or lymphoma had higher levels of cryocrit with cryoglobulinemic syndrome comparable to that found in HCV-positive MC patients.
  • MC is a multifactorial disorder; considering possible etiological factors and clinical associations the disease may present different subsets: the prevalent group of HCV-positive MC; HCV-positive MC associated with different autoimmune lymphoproliferative disorders; two MC subsets without any apparent causative agent: those with well-known autoimmune lymphoproliferative disorders and the rare cases of "essential" MC; and finally MC associated with other infectious agents.

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  • (PMID = 17936226.001).
  • [ISSN] 1878-3562
  • [Journal-full-title] Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
  • [ISO-abbreviation] Dig Liver Dis
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Netherlands
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13. Manganelli P, Fietta P, Quaini F: Hematologic manifestations of primary Sjögren's syndrome. Clin Exp Rheumatol; 2006 Jul-Aug;24(4):438-48
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  • [Title] Hematologic manifestations of primary Sjögren's syndrome.
  • Sjögren's syndrome (SS) is a chronic autoimmune disorder, primarily characterized by the mononuclear cell infiltration of exocrine glands exiting in parenchymal damage and secretory impairment.
  • The spectrum of the disease extends from an autoimmune exocrinopathy to a systemic process with extraglandular manifestations.
  • SS is defined as primary (pSS) when isolated, or secondary when associated with another autoimmune disease.
  • Patients with pSS may present hematologic abnormalities, such as anemia, hemocytopenias, monoclonal gammopathies and lymphoprolipherative disorders, predominantly non-Hodgkin's lymphoma of B-cell origin.
  • [MeSH-major] Hematologic Diseases / etiology. Sjogren's Syndrome / complications
  • [MeSH-minor] Autoimmunity. Humans. Lymphoproliferative Disorders

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  • (PMID = 16956437.001).
  • [ISSN] 0392-856X
  • [Journal-full-title] Clinical and experimental rheumatology
  • [ISO-abbreviation] Clin. Exp. Rheumatol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Italy
  • [Number-of-references] 147
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14. López-Anglada L, Puig N, Díez-Campelo M, Alonso-Ralero L, Barrena S, Aparicio MA, Gutiérrez NC, García-Sanz R: Monoclonal free light chains can be found in heavy chain diseases. Ann Clin Biochem; 2010 Nov;47(Pt 6):570-2
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  • Heavy chain diseases (HCDs) are rare B-cell lymphoproliferative neoplasias characterized by the production of a monoclonal component consisting of a truncated monoclonal Ig heavy chain without the associated light chain.
  • In the work-up of the patient, the underlying anatomopathological lymphoproliferative disease corresponded to a lymphoplasmacytic lymphoma, as it is stated in the current World Health Organization classification (2008), with both lymphadenopathic and bone marrow infiltration.
  • As in other cases, several autoimmune manifestations (antiphospholipidic syndrome and immune thrombocytopenia) were present during the course of the disease in this patient.

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  • (PMID = 20930031.001).
  • [ISSN] 1758-1001
  • [Journal-full-title] Annals of clinical biochemistry
  • [ISO-abbreviation] Ann. Clin. Biochem.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Immunoglobulin gamma-Chains
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15. Zignego AL, Ferri C, Pileri SA, Caini P, Bianchi FB, Italian Association of the Study of Liver Commission on Extrahepatic Manifestations of HCV infection: Extrahepatic manifestations of Hepatitis C Virus infection: a general overview and guidelines for a clinical approach. Dig Liver Dis; 2007 Jan;39(1):2-17
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  • Hepatitis C Virus is associated with a wide series of extrahepatic manifestations.
  • Hepatitis C Virus-related lymphoproliferative disorders, whose prototype is mixed cryoglobulinaemia, represent the most closely related extrahepatic manifestations of Hepatitis C Virus.
  • Other Hepatitis C Virus-associated disorders include nephropathies, thyreopathies, sicca syndrome, idiopathic pulmonary fibrosis, porphyria cutanea tarda, lichen planus, diabetes, chronic polyarthritis, cardiopathy and atherosclerosis.
  • The aim of the present paper is to outline the most recent evidence concerning extrahepatic disorders that are possibly associated with Hepatitis C Virus infection.
  • [MeSH-minor] Autoimmune Diseases / etiology. Autoimmune Diseases / immunology. Cryoglobulinemia / etiology. Cryoglobulinemia / immunology. Humans. Lichen Planus / etiology. Lichen Planus / immunology. Lymphoma, B-Cell / etiology. Lymphoma, B-Cell / immunology. Lymphoproliferative Disorders / epidemiology. Lymphoproliferative Disorders / etiology. Paraproteinemias / etiology. Paraproteinemias / immunology. Porphyria Cutanea Tarda / etiology. Porphyria Cutanea Tarda / immunology

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  • [CommentIn] Dig Liver Dis. 2008 Aug;40(8):707-8; author reply 708 [18450527.001]
  • (PMID = 16884964.001).
  • [ISSN] 1590-8658
  • [Journal-full-title] Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
  • [ISO-abbreviation] Dig Liver Dis
  • [Language] eng
  • [Publication-type] Journal Article; Practice Guideline; Review
  • [Publication-country] Netherlands
  • [Number-of-references] 236
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16. Alcântara C, Gomes MJ, Ferreira C: Rituximab therapy in primary Sjögren's syndrome. Ann N Y Acad Sci; 2009 Sep;1173:701-5
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  • [Title] Rituximab therapy in primary Sjögren's syndrome.
  • Primary Sjögren's syndrome is an autoimmune disease characterized by lymphocytic infiltration of glandular tissues leading to sicca symptoms, namely, dry eyes and dry mouth.
  • A small but not insignificant percentage of those patients evolve to B cell lymphoma.
  • The increased expression of B cell survival factors, such as B cell activating factor, may promote the perpetuation of a B cell clone and precede the lymphoproliferative disease.
  • Rituximab, a chimeric monoclonal antibody to CD20, leads to B cell depletion and may have a role in Sjögren systemic manifestations as well as in preventing and treating Sjögren-associated lymphoma.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Antigens, CD20 / immunology. Sjogren's Syndrome / drug therapy

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  • (PMID = 19758218.001).
  • [ISSN] 1749-6632
  • [Journal-full-title] Annals of the New York Academy of Sciences
  • [ISO-abbreviation] Ann. N. Y. Acad. Sci.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Antigens, CD20; 0 / Antirheumatic Agents; 0 / B-Cell Activating Factor; 4F4X42SYQ6 / Rituximab
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17. Berger F, Traverse-Glehen A, Felman P, Callet-Bauchu E, Baseggio L, Gazzo S, Thieblemont C, Ffrench M, Magaud JP, Salles G, Coiffer B: Clinicopathologic features of Waldenstrom's macroglobulinemia and marginal zone lymphoma: are they distinct or the same entity? Clin Lymphoma; 2005 Mar;5(4):220-4
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  • [Title] Clinicopathologic features of Waldenstrom's macroglobulinemia and marginal zone lymphoma: are they distinct or the same entity?
  • Waldenstrom's macroglobulinemia (WM) is considered in the World Health Organization classification as a clinical syndrome associated with monoclonal immunoglobulin (Ig) M secretion, mainly observed in patients with lymphoplasmacytic lymphoma (LPL) and occasionally with other small B-cell lymphomas.
  • Some authors consider it a rare distinct lymphoproliferative disorder with primary bone marrow infiltration and IgM monoclonal gammopathy.
  • Extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, nodal MZL (NMZL), and splenic MZL (SMZL) are distinct entities displaying common morphologic, immunophenotypic, and genetic characteristics.
  • MALT lymphoma is clearly distinct from LPL, although bone marrow infiltration and IgM paraprotein are not rare.
  • Splenic MZL and NMZL are incompletely characterized, but a plasmacytoid/plasmacytic differentiation, autoimmune manifestations, and monoclonal component are frequent in both diseases.
  • [MeSH-major] Antigens, CD. Leukemia, Lymphocytic, Chronic, B-Cell / classification. Leukemia, Lymphocytic, Chronic, B-Cell / immunology. Lymphoma, B-Cell / immunology. Lymphoma, B-Cell / pathology. Waldenstrom Macroglobulinemia / classification. Waldenstrom Macroglobulinemia / immunology

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  • (PMID = 15794852.001).
  • [ISSN] 1526-9655
  • [Journal-full-title] Clinical lymphoma
  • [ISO-abbreviation] Clin Lymphoma
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD; 0 / Immunoglobulin M
  • [Number-of-references] 38
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18. Tilakaratne W, Dissanayake M: Paraneoplastic pemphigus: a case report and review of literature. Oral Dis; 2005 Sep;11(5):326-9
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  • Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease frequently associated with lymphoproliferative disorders.
  • Most patients develop very severe oral ulceration and conjunctival ulceration with or without genital ulceration resembling the features of Steven's Johnson's syndrome or most severe forms of drug eruptions.
  • We document a case of PNP in a 29-year-old female who suffers from non-Hodgkin's lymphoma.
  • [MeSH-major] Lymphoma, Non-Hodgkin / complications. Oral Ulcer / etiology. Paraneoplastic Syndromes / pathology. Pemphigus / pathology

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  • (PMID = 16120122.001).
  • [ISSN] 1354-523X
  • [Journal-full-title] Oral diseases
  • [ISO-abbreviation] Oral Dis
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Denmark
  • [Chemical-registry-number] 0 / Anti-Inflammatory Agents
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19. Libra M, Indelicato M, De Re V, Zignego AL, Chiocchetti A, Malaponte G, Dianzani U, Nicoletti F, Stivala F, McCubrey JA, Mazzarino MC: Elevated Serum Levels of Osteopontin in HCV-Associated Lymphoproliferative Disorders. Cancer Biol Ther; 2005 Nov;4(11):1192-4
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  • [Title] Elevated Serum Levels of Osteopontin in HCV-Associated Lymphoproliferative Disorders.
  • Hepatitis C virus (HCV) infection is associated with chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
  • Recent evidences have also suggested that HCV infection contributes to development of autoimmune disorders and B-cell nonHodgkin's lymphoma (NHL).
  • Increased serum osteopontin (OPN) levels have been associated with several autoimmune diseases as well as a variety of cancers.
  • However, the association between OPN and B-cell NHL or HCV-associated B-cell proliferation has not previously been reported.
  • In the present study, we determined whether serum OPN differences were associated with HCV infection, type II mixed cryglobulinemia (MC) syndrome and B-cell NHL.
  • Our results show that high serum OPN levels are associated with B-cell NHL and HCV infection.
  • Interestingly, highest serum OPN concentrations were found among HCV-infected patients with concomitant type II MC syndrome with and without B-cell NHL.
  • These data indicate that OPN is involved in the lymphomagenesis, especially, in the context of HCV infection and autoimmune diseases.
  • [MeSH-major] Cryoglobulinemia / virology. Hepatitis C / complications. Lymphoma, B-Cell / virology. Sialoglycoproteins / blood

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  • (PMID = 16177564.001).
  • [ISSN] 1538-4047
  • [Journal-full-title] Cancer biology & therapy
  • [ISO-abbreviation] Cancer Biol. Ther.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA098195
  • [Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / RNA, Viral; 0 / SPP1 protein, human; 0 / Sialoglycoproteins; 106441-73-0 / Osteopontin
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20. Vezzoli P, Berti E, Marzano AV: Rationale and efficacy for the use of rituximab in paraneoplastic pemphigus. Expert Rev Clin Immunol; 2008 May;4(3):351-63
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  • Paraneoplastic pemphigus (PNP) is a life-threatening, autoimmune, blistering-skin disease, associated with various neoplasms, particularly lymphoproliferative disorders.
  • To define this condition, the encompassing term 'paraneoplastic autoimmune multiorgan syndrome' has also been suggested.
  • The anti-CD20 monoclonal antibody, rituximab, was successfully administered to two patients with PNP and CD20(+) follicular lymphoma in 2001.
  • Since then, good responses to rituximab by different refractory autoimmune disorders have been reported, but further controlled trials are warranted to evaluate the effectiveness and safety of this agent as a second-line treatment for PNP.

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  • (PMID = 20476925.001).
  • [ISSN] 1744-8409
  • [Journal-full-title] Expert review of clinical immunology
  • [ISO-abbreviation] Expert Rev Clin Immunol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
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21. Martínez-Hernández E, Rosenfeld MR, Pruitt A, Dalmau J: [Neurological complications of transplantation]. Neurologia; 2008 Jul-Aug;23(6):373-86
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  • Neurological complications associated with these procedures remain frequent.
  • In general, the main neurological problems of HCT and organ transplantation include metabolic and toxic encephalopathies, and central and peripheral neurological disorders caused by coagulopathy, infections, and autoimmune mechanisms.
  • The term post-transplant lymphoproliferative disorder (PTLD) includes a spectrum of disorders ranging from benign polyclonal lymphoid hyperplasia to malignant monoclonal lymphoma, usually related to the Epstein-Barr virus.
  • Some lesser known syndromes such as the immune reconstitution inflammatory syndrome and paraneoplastic neuropathies related with PTLD are increasingly being described and need to be considered in the evaluation of a transplant patient with neurological problems.

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  • (PMID = 18597192.001).
  • [ISSN] 0213-4853
  • [Journal-full-title] Neurología (Barcelona, Spain)
  • [ISO-abbreviation] Neurologia
  • [Language] spa
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Spain
  • [Chemical-registry-number] 0 / Immunosuppressive Agents
  • [Number-of-references] 109
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22. Gualco G, van den Berg A, Koopmans S, Bacchi LM, Carneiro SS, Ruiz E Jr, Vecchi AP, Chan JK: Autoimmune lymphoproliferative syndrome in a patient with a new minimal deletion in the death domain of the FAS gene. Hum Pathol; 2008 Jan;39(1):137-41
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  • [Title] Autoimmune lymphoproliferative syndrome in a patient with a new minimal deletion in the death domain of the FAS gene.
  • We present a case of autoimmune lymphoproliferative syndrome (ALPS) caused by a previously undescribed minimal deletion in the death domain of the FAS gene.
  • ALPS is an uncommon disease associated with an impaired Fas-mediated apoptosis.
  • The patient presented with a history of splenomegaly since 4 months of age, associated with cervical lymphadenopathy, which improved with oral corticosteroid treatment.
  • Some clear cells were also present, raising the suspicion of malignant lymphoma.
  • [MeSH-major] Autoimmune Diseases / genetics. Fas-Associated Death Domain Protein / genetics. Lymphoproliferative Disorders / genetics. Sequence Deletion

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  • (PMID = 18070632.001).
  • [ISSN] 0046-8177
  • [Journal-full-title] Human pathology
  • [ISO-abbreviation] Hum. Pathol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 070058; United States / NCI NIH HHS / CA / CA 082274
  • [Publication-type] Case Reports; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD95; 0 / Fas-Associated Death Domain Protein
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23. Ramos-Casals M, De Vita S, Tzioufas AG: Hepatitis C virus, Sjögren's syndrome and B-cell lymphoma: linking infection, autoimmunity and cancer. Autoimmun Rev; 2005 Jan;4(1):8-15
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Hepatitis C virus, Sjögren's syndrome and B-cell lymphoma: linking infection, autoimmunity and cancer.
  • An increased prevalence of hematologic malignancies is often described in patients with Sjögren's syndrome (SS).
  • Viruses have been proposed as possible etiologic or triggering agents of systemic autoimmune diseases (SADs), with hepatitis C virus (HCV) being one of the viruses most frequently associated with autoimmune features and with systemic autoimmune diseases such as mixed cryoglobulinemia or SS.
  • Moreover, the association between HCV infection and hematologic malignancies, mainly non-Hodgkin's lymphoma (NHL), is supported by several studies.
  • For these reasons, the recognized association of specific systemic autoimmune diseases (mainly SS and mixed cryoglobulinemia) with HCV infection, added to the possible evolution of any one of these entities into a B-cell NHL, suggests the possibility of a close relationship among SS, HCV and B-cell lymphoproliferative disorders, especially in patients with type II mixed cryoglobulinemia.
  • [MeSH-major] Autoimmunity / immunology. Hepacivirus / immunology. Hepatitis C / immunology. Lymphoma, B-Cell / immunology. Sjogren's Syndrome / immunology

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  • (PMID = 15652773.001).
  • [ISSN] 1568-9972
  • [Journal-full-title] Autoimmunity reviews
  • [ISO-abbreviation] Autoimmun Rev
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Autoantigens; 0 / Ribonucleoproteins; 0 / SS-A antigen; 0 / SS-B antigen
  • [Number-of-references] 32
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24. Venkataraman G, McClain KL, Pittaluga S, Rao VK, Jaffe ES: Development of disseminated histiocytic sarcoma in a patient with autoimmune lymphoproliferative syndrome and associated Rosai-Dorfman disease. Am J Surg Pathol; 2010 Apr;34(4):589-94
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  • [Title] Development of disseminated histiocytic sarcoma in a patient with autoimmune lymphoproliferative syndrome and associated Rosai-Dorfman disease.
  • Patients with autoimmune lymphoproliferative syndrome (ALPS) have defective lymphocyte apoptosis with increased risk for lymphoid malignancies.
  • Herein, we report a patient with ALPS who developed histiocytic sarcoma in a background of sinus histiocytosis and massive lymphadenopathy or Rosai- Dorfman disease.
  • This patient had documented ALPS type Ia with a germline missense mutation in exon 9 of the TNFRSF6 gene (973 A>T, D244V) encoding Fas (CD95/Apo-1).
  • He presented at 10 months with hepatosplenomegaly and autoimmune hemolytic anemia and was diagnosed with ALPS.
  • At the age of 6 (1/2) years, he developed classic Hodgkin lymphoma which was treated using standard chemotherapy.
  • Two years later, a biopsy of a positron emission tomography-positive axillary node showed features of ALPS and focal involvement by sinus histiocytosis and massive lymphadenopathy.
  • Thereafter, the patient continued to have continued lymphadenopathy and progressive splenomegaly, leading to exploratory surgery at the age of 13 years for suspicion of lymphoma.
  • The occurrence of malignancies involving 2 separate hematopoietic lineages in ALPS has not been reported earlier.
  • Given the central role of defective Fas signaling in ALPS, histiocytes may be yet another lineage at risk for neoplastic transformation secondary to a block in apoptosis.
  • [MeSH-major] Autoimmune Lymphoproliferative Syndrome / pathology. Histiocytic Sarcoma / pathology. Histiocytosis, Sinus / pathology

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  • (PMID = 20216376.001).
  • [ISSN] 1532-0979
  • [Journal-full-title] The American journal of surgical pathology
  • [ISO-abbreviation] Am. J. Surg. Pathol.
  • [Language] eng
  • [Grant] United States / Intramural NIH HHS / / Z01 SC000550-27; United States / Intramural NIH HHS / / ZIA SC000550-29
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD95; 0 / Biomarkers, Tumor; 0 / FAS protein, human
  • [Other-IDs] NLM/ NIHMS190086; NLM/ PMC2861546
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25. Silvana B, Antonella LM, Basilia P, Trombetta D, Saija A, Salpietro C: Rituximab for the treatment of post-bone marrow transplantation refractory hemolytic anemia in a child with Omenn's syndrome. Pediatr Transplant; 2007 Aug;11(5):552-6
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  • [Title] Rituximab for the treatment of post-bone marrow transplantation refractory hemolytic anemia in a child with Omenn's syndrome.
  • Omenn's syndrome is a rare severe combined immunodeficiency that kills affected subjects before the end of the first year of life unless patients are treated with bone marrow transplantation (BMT).
  • Unfortunately, post-BMT patients may develop autoimmune diseases, such as autoimmune hemolytic anemia (AIHA), which sometimes fails to respond to standard therapies.
  • Rituximab is currently only labeled for treatment of B-cell lymphoproliferative disorders, such as B-cell non-Hodgkin's lymphoma and follicular lymphoma; however, it is also employed in the treatment of a variety of disorders mediated by auto-antibodies, such as AIHA and transplant-related autoimmune disorders.
  • Herein, we describe the case of a 23-month-old male child with Omenn's syndrome, who had undergone BMT and was successfully treated with rituximab (375 mg/m(2) intravenously, weekly for three times) for refractory post-BMT hemolytic anemia.
  • Our findings evidence that rituximab should be considered for treatment of post-BMT AIHA refractory to traditional therapy also in children with primary immunodeficiencies; furthermore, rituximab might represent a means to obtain remissions without the toxic effects associated with corticosteroid and immunosuppressive agents.
  • [MeSH-minor] Antibodies, Monoclonal, Murine-Derived. Antigens, CD20. Follow-Up Studies. Humans. Infant. Injections, Intravenous. Male. Postoperative Complications. Rituximab. Syndrome

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  • (PMID = 17631027.001).
  • [ISSN] 1397-3142
  • [Journal-full-title] Pediatric transplantation
  • [ISO-abbreviation] Pediatr Transplant
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Denmark
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Antigens, CD20; 0 / Immunologic Factors; 4F4X42SYQ6 / Rituximab
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26. Papiris SA, Tsonis IA, Moutsopoulos HM: Sjögren's Syndrome. Semin Respir Crit Care Med; 2007 Aug;28(4):459-71
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  • [Title] Sjögren's Syndrome.
  • Sjögren's syndrome (SS) is a chronic, slowly progressive, inflammatory, autoimmune disease characterized by (1) lymphocytic infiltration of the exocrine glands leading to diminished or absent glandular secretion, and (2) marked B-lymphocytic cell hyperreactivity manifested initially by a variety of serum autoantibodies, including those against the Ro(SSA) and La(SSB) ribonucleoproteins, ending in the development of B cell non-Hodgkin's lymphoma in a substantial number of patients.
  • (2) a wide spectrum of lymphoproliferative diseases, ranging from bronchus-associated lymphoid tissue (BALT) hyperplasia, lymphoid interstitial pneumonia, and B cell non-Hodgkin's lymphoma mainly of the extranodal marginal zone B-cell lymphoma of BALT-type or rarely of higher-grade malignancy; and (3) other interstitial pneumonias.
  • Pleuritis can be seen in SS patients with associated systemic lupus erythematosus or rheumatoid arthritis.
  • [MeSH-major] Lung Diseases, Interstitial / etiology. Respiratory Tract Diseases / etiology. Sjogren's Syndrome / complications
  • [MeSH-minor] Humans. Lymphoproliferative Disorders / etiology. Prognosis. Respiratory Function Tests


27. Cugno M, Castelli R, Cicardi M: Angioedema due to acquired C1-inhibitor deficiency: a bridging condition between autoimmunity and lymphoproliferation. Autoimmun Rev; 2008 Dec;8(2):156-9
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  • Angioedema due to an acquired deficiency in the inhibitor of the first component of human complement (CI-INH) is a rare syndrome that is usually identified as acquired angioedema (AAE).
  • AAE is frequently associated with lymphoproliferative diseases ranging from monoclonal gammopathies of uncertain significance (MGUS) to non-Hodgkin's lymphoma (NHL) and/or anti-C1-INH inactivating autoantibodies.
  • The coexistence of true B cell malignancy, non-malignant B cell proliferation and pathogenic autoimmune responses suggests that AAE patients are all affected by altered B cell proliferation control although their clinical evolution may vary.
  • [MeSH-major] Angioedema / etiology. Autoimmunity. Complement C1 Inhibitor Protein / metabolism. Lymphoproliferative Disorders / immunology

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  • (PMID = 19014872.001).
  • [ISSN] 1873-0183
  • [Journal-full-title] Autoimmunity reviews
  • [ISO-abbreviation] Autoimmun Rev
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Complement C1 Inhibitor Protein
  • [Number-of-references] 30
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28. Hong YH, Lee CK: Autoimmune lymphoproliferative syndrome-like syndrome presented as lupus-like syndrome with mycobacterial joint infection evolved into the lymphoma. Rheumatol Int; 2009 Mar;29(5):569-73
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  • [Title] Autoimmune lymphoproliferative syndrome-like syndrome presented as lupus-like syndrome with mycobacterial joint infection evolved into the lymphoma.
  • The autoimmune lymphoproliferative syndrome (ALPS) and ALPS-like syndrome are variable clinical conditions characterized by lymphoproliferative disease, autoimmune cytopenias and susceptibility to malignancy.
  • A low-grade fever, intermittent hypotension and confusion were associated with the pain.
  • But with the symptoms worsening, the patient developed cervical lymph node enlargements and was diagnosed as a diffuse large B cell lymphoma with hemophagocytosis on biopsy.
  • [MeSH-major] Autoimmune Diseases / pathology. Joints / pathology. Lymphoma, Large B-Cell, Diffuse / pathology. Lymphoproliferative Disorders / pathology. Mycobacterium Infections / pathology
  • [MeSH-minor] Anti-Bacterial Agents / therapeutic use. Anti-Inflammatory Agents, Non-Steroidal / therapeutic use. Female. Glucocorticoids / therapeutic use. Humans. Lupus Erythematosus, Systemic / pathology. Middle Aged. Syndrome


29. Ramos-Casals M, Brito-Zerón P, Yagüe J, Akasbi M, Bautista R, Ruano M, Claver G, Gil V, Font J: Hypocomplementaemia as an immunological marker of morbidity and mortality in patients with primary Sjogren's syndrome. Rheumatology (Oxford); 2005 Jan;44(1):89-94
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  • [Title] Hypocomplementaemia as an immunological marker of morbidity and mortality in patients with primary Sjogren's syndrome.
  • OBJECTIVE: To analyse the prevalence and clinical significance of hypocomplementaemia in a large series of patients with primary Sjogren's syndrome (SS), focusing on the association of low complement levels with clinical manifestations, immunological features, lymphoproliferative disorders and mortality.
  • We also analysed complement levels in 46 patients with SS associated with hepatitis C virus (HCV) infection and 184 with HCV-related cryoglobulinaemia as control groups.
  • In the multivariate analysis, patients with low C4 levels showed a higher prevalence of peripheral neuropathy, cutaneous vasculitis, RF, cryoglobulins and lymphoma compared with those with normal C4 levels.
  • CONCLUSION: Hypocomplementaemia is closely associated with systemic expression and adverse outcomes (lymphoma development and death) in patients with primary SS.
  • [MeSH-major] Complement System Proteins / deficiency. Sjogren's Syndrome / immunology
  • [MeSH-minor] Aged. Biomarkers / blood. Complement C3 / analysis. Complement C3 / deficiency. Complement C4 / analysis. Complement C4 / deficiency. Complement Hemolytic Activity Assay. Female. Hepatitis C, Chronic / complications. Hepatitis C, Chronic / immunology. Humans. Lymphoma / etiology. Lymphoma / immunology. Male. Middle Aged. Prospective Studies. Survival Analysis

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  • (PMID = 15381790.001).
  • [ISSN] 1462-0324
  • [Journal-full-title] Rheumatology (Oxford, England)
  • [ISO-abbreviation] Rheumatology (Oxford)
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Biomarkers; 0 / Complement C3; 0 / Complement C4; 9007-36-7 / Complement System Proteins
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30. Ramos-Casals M, Font J: Extrahepatic manifestations in patients with chronic hepatitis C virus infection. Curr Opin Rheumatol; 2005 Jul;17(4):447-55
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  • PURPOSE OF REVIEW: Chronic hepatitis C virus infection often has autoimmune clinical and analytic features.
  • This review analyzes recent data on the close association of chronic hepatitis C virus infection with autoimmune and lymphoproliferative processes.
  • RECENT FINDINGS: Hepatitis C virus infection has been associated with both organ-specific (thyroiditis, diabetes) and systemic autoimmune diseases.
  • Experimental, virologic, and clinical evidence has demonstrated a close association between hepatitis C virus infection and Sjögren syndrome, with hepatitis C virus-associated Sjögren syndrome being indistinguishable in most cases from the primary form.
  • Hepatitis C virus has also been associated with an atypical presentation of antiphospholipid syndrome, as well as with the development of sarcoidosis.
  • A higher prevalence of hematologic processes in patients with hepatitis C virus infection has recently been reported, including cytopenias and lymphoproliferative disorders.
  • Recent data are available on the use of new immunosuppressive and biologic agents (mainly mycophenolate mofetil, anti-tumor necrosis factor agents, and rituximab) in patients with hepatitis C virus infection and autoimmune or lymphoproliferative manifestations.
  • SUMMARY: There is increasing evidence of a close association of hepatitis C virus infection with autoimmune and hematologic processes.
  • The sialotropism of hepatitis C virus may explain the close association with Sjögren syndrome, and its lymphotropism links the virus to cryoglobulinemia, autoimmune cytopenias, and lymphoma.
  • The substantial overlap between cryoglobulinemic features and the classification criteria for some systemic autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, and polyarteritis nodosa) make the differentiation between mimicking and coexistence difficult.
  • [MeSH-major] Autoimmune Diseases / complications. Hepatitis C, Chronic / complications. Lymphoproliferative Disorders / complications

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  • (PMID = 15956842.001).
  • [ISSN] 1040-8711
  • [Journal-full-title] Current opinion in rheumatology
  • [ISO-abbreviation] Curr Opin Rheumatol
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Number-of-references] 111
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31. Fabris M, Quartuccio L, Sacco S, De Marchi G, Pozzato G, Mazzaro C, Ferraccioli G, Migone TS, De Vita S: B-Lymphocyte stimulator (BLyS) up-regulation in mixed cryoglobulinaemia syndrome and hepatitis-C virus infection. Rheumatology (Oxford); 2007 Jan;46(1):37-43
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  • [Title] B-Lymphocyte stimulator (BLyS) up-regulation in mixed cryoglobulinaemia syndrome and hepatitis-C virus infection.
  • OBJECTIVES: To investigate the role of B-Lymphocyte stimulator (BLyS) in mixed cryoglobulinaemia syndrome (MCsn), a systemic vasculitis associated with a high risk to develop lymphoma, since BLyS up-regulation may favour both autoimmunity and lymphoproliferation.
  • High BLyS levels were significantly associated only with MCsn-related overt lymphoproliferative disorder.
  • CONCLUSIONS: BLyS is up-regulated and may play a pathogenetic role in a fraction of patients with MCsn, similarly to other autoimmune diseases.
  • [MeSH-major] Autoimmune Diseases / immunology. B-Cell Activating Factor / blood. Cryoglobulinemia / immunology. Hepatitis C / immunology. Up-Regulation
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antiviral Agents / therapeutic use. Enzyme-Linked Immunosorbent Assay / methods. Female. Humans. Male. Middle Aged. Syndrome

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  • (PMID = 16735452.001).
  • [ISSN] 1462-0324
  • [Journal-full-title] Rheumatology (Oxford, England)
  • [ISO-abbreviation] Rheumatology (Oxford)
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antiviral Agents; 0 / B-Cell Activating Factor
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32. Rao VK, Price S, Perkins K, Aldridge P, Tretler J, Davis J, Dale JK, Gill F, Hartman KR, Stork LC, Gnarra DJ, Krishnamurti L, Newburger PE, Puck J, Fleisher T: Use of rituximab for refractory cytopenias associated with autoimmune lymphoproliferative syndrome (ALPS). Pediatr Blood Cancer; 2009 Jul;52(7):847-52
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  • [Title] Use of rituximab for refractory cytopenias associated with autoimmune lymphoproliferative syndrome (ALPS).
  • BACKGROUND: ALPS is a disorder of apoptosis resulting in accumulation of autoreactive lymphocytes, leading to marked lymphadenopathy, hepatosplenomegaly, and multilineage cytopenias due to splenic sequestration and/or autoimmune destruction often presenting in childhood.
  • We summarize our experience of rituximab use during the last 8 years in 12 patients, 9 children, and 3 adults, out of 259 individuals with ALPS, belonging to 166 families currently enrolled in studies at the National Institutes of Health.
  • METHODS: Refractory immune thrombocytopenia (platelet count <20,000) in nine patients and autoimmune hemolytic anemia (AIHA) in three patients led to treatment with rituximab.
  • RESULTS: In seven out of nine patients with ALPS and thrombocytopenia, rituximab therapy led to median response duration of 21 months (range 14-36 months).
  • Long-term follow-up of ALPS patients with cytopenias after any treatment is necessary to determine relative risks and benefits.

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  • [Copyright] (c) 2009 Wiley-Liss, Inc.
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  • (PMID = 19214977.001).
  • [ISSN] 1545-5017
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] ENG
  • [Grant] United States / CCR NIH HHS / RC / HHSN261200800001C; United States / NCI NIH HHS / CA / HHSN261200800001E; United States / Intramural NIH HHS / / Z99 AI999999; United States / PHS HHS / / HHSN261200800001E
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Immunosuppressive Agents; 4F4X42SYQ6 / Rituximab
  • [Other-IDs] NLM/ NIHMS123735; NLM/ PMC2774763
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33. Quartuccio L, Fabris M, Salvin S, Maset M, De Marchi G, De Vita S: Controversies on rituximab therapy in sjögren syndrome-associated lymphoproliferation. Int J Rheumatol; 2009;2009:424935
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  • [Title] Controversies on rituximab therapy in sjögren syndrome-associated lymphoproliferation.
  • Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of salivary and lachrymal glands, and frequently accompanied by systemic symptoms.
  • A subgroup of SS patients develops malignant B cell non-Hodgkin's lymphoma (NHL), usually of the mucosa-associated lymphoid tissue (MALT) type and very often located in the major salivary glands.
  • Rituximab (RTX), a chimeric monoclonal antibody targeting the CD20 antigen on the B cell surface, has been successfully investigated in other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, ANCA-associated vasculitis, and mixed cryoglobulinemic syndrome.
  • Preliminary experiences of RTX therapy in SS patients with or without a lymphoproliferative disorder suggest that SS patients with more residual exocrine gland function might better benefit from RTX.
  • Efficacy of RTX in SS-associated B-cell lymphoma, mainly in low-grade salivary gland lymphomas, remains an open issue.

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  • (PMID = 20148068.001).
  • [ISSN] 1687-9279
  • [Journal-full-title] International journal of rheumatology
  • [ISO-abbreviation] Int J Rheumatol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Egypt
  • [Other-IDs] NLM/ PMC2817502
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34. Liebman H: Other immune thrombocytopenias. Semin Hematol; 2007 Oct;44(4 Suppl 5):S24-34
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Commonly occurring conditions associated with secondary ITP include lymphoproliferative disorders (chronic lymphocytic leukemia [CLL], Hodgkin's disease and non-Hodgkin's lymphomas), autoimmune collagen vascular diseases (systemic lupus erythematosus [SLE], thyroid disease, antiphospholipid syndrome [APS]), and chronic infections (human immunodeficiency virus [HIV], Helicobacter pylori, hepatitis C virus [HCV]).
  • The mechanism of platelet destruction in thrombocytopenias associated with lymphoproliferative disorders and collagen vascular diseases is identical to the autoimmune mechanism seen in primary ITP.
  • Platelet destruction in infection-associated ITP occurs via various mechanisms including accelerated platelet clearance due to immune complex disease as seen in HIV infection or cross-reactivity of anti-platelet glycoprotein antibodies and viral antigens in HIV, HCV, and H pylori infections (antigenic mimicry).
  • [MeSH-minor] Acquired Immunodeficiency Syndrome / complications. Acquired Immunodeficiency Syndrome / drug therapy. Acquired Immunodeficiency Syndrome / immunology. Antiphospholipid Syndrome / complications. Antiphospholipid Syndrome / drug therapy. Antiphospholipid Syndrome / immunology. Diagnosis, Differential. Female. Helicobacter Infections / complications. Helicobacter Infections / drug therapy. Helicobacter Infections / immunology. Hepatitis C / complications. Hepatitis C / drug therapy. Hepatitis C / immunology. Humans. Leukemia / complications. Leukemia / drug therapy. Leukemia / immunology. Lupus Erythematosus, Systemic / complications. Lupus Erythematosus, Systemic / drug therapy. Lupus Erythematosus, Systemic / immunology. Lymphoma / complications. Lymphoma / immunology. Lymphoma / therapy. Male. Platelet Count. Thyroid Diseases / complications. Thyroid Diseases / immunology. Thyroid Diseases / therapy


37. Vacek MM, Schäffer AA, Davis J, Fischer RE, Dale JK, Adams S, Straus SE, Puck JM: HLA B44 is associated with decreased severity of autoimmune lymphoproliferative syndrome in patients with CD95 defects (ALPS type Ia). Clin Immunol; 2006 Jan;118(1):59-65
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] HLA B44 is associated with decreased severity of autoimmune lymphoproliferative syndrome in patients with CD95 defects (ALPS type Ia).
  • Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte apoptosis characterized by non-malignant lymphadenopathy and splenomegaly, expansion of T cells without either CD4 or CD8 surface markers, and increased incidence of autoimmune diseases and lymphoma.
  • Most patients with ALPS have dominant, heterozygous mutations in tumor necrosis factor receptor superfamily member 6 (TNFRSF6), which encodes CD95, also known as Fas, a mediator of apoptosis.
  • Penetrance and range of disease manifestations in ALPS are highly variable, even among family members who share the same dominant TNFRSF6 mutation.
  • To evaluate HLA as a candidate modifier locus, we typed HLA A, B (including subtypes), and DQB alleles in 356 individuals from 63 unrelated families with defined TNFRSF6 mutations associated with ALPS.
  • Among the healthier, mutation-bearing individuals, transmission of HLA B44 was significantly overrepresented (nominal P<0.0074) as compared to transmission in patients with severe clinical features of ALPS.
  • The B44 allele may exert a protective role in ALPS.
  • [MeSH-major] Antigens, CD95 / genetics. Autoimmune Diseases / genetics. HLA-B Antigens / genetics. HLA-B Antigens / physiology. Lymphoproliferative Disorders / genetics. Lymphoproliferative Disorders / immunology. Severity of Illness Index
  • [MeSH-minor] Alleles. Data Interpretation, Statistical. Gene Frequency. HLA-B44 Antigen. HLA-DQ Antigens / genetics. HLA-DQ beta-Chains. Histocompatibility Testing. Humans. Mutation. Receptors, Tumor Necrosis Factor / genetics. Syndrome

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  • (PMID = 16257267.001).
  • [ISSN] 1521-6616
  • [Journal-full-title] Clinical immunology (Orlando, Fla.)
  • [ISO-abbreviation] Clin. Immunol.
  • [Language] eng
  • [Grant] United States / Intramural NIH HHS / /
  • [Publication-type] Journal Article; Research Support, N.I.H., Intramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD95; 0 / FAS protein, human; 0 / HLA-B Antigens; 0 / HLA-B44 Antigen; 0 / HLA-DQ Antigens; 0 / HLA-DQ beta-Chains; 0 / HLA-DQB1 antigen; 0 / HLA-Dx antigen; 0 / Receptors, Tumor Necrosis Factor
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38. Tran H, Nourse J, Hall S, Green M, Griffiths L, Gandhi MK: Immunodeficiency-associated lymphomas. Blood Rev; 2008 Sep;22(5):261-81
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Immunodeficiency-associated lymphomas.
  • This article covers lymphoproliferative disorders in patients with primary or acquired immunodeficiencies.
  • Primary immunodeficiences include Ataxia Telangiectasia and X-linked disorders such as Wiskott-Aldrich syndrome.
  • Evidence for lymphoma developing as a result of treatment with methotrexate or Tumour Necrosis Factor Antagonists for autoimmune entities will also be reviewed.
  • Lastly, discussion will centre on mechanisms utilized by lymphomas in the immunodeficient as these may have applications to lymphomas in the "immunocompetent", by serving as a paradigm for the altered immunoregulatory environment present in many lymphoma sub-types.
  • [MeSH-major] Immunocompromised Host / immunology. Immunologic Deficiency Syndromes / immunology. Lymphoma / immunology

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  • (PMID = 18456377.001).
  • [ISSN] 0268-960X
  • [Journal-full-title] Blood reviews
  • [ISO-abbreviation] Blood Rev.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Scotland
  • [Chemical-registry-number] 0 / Tumor Necrosis Factor-alpha; YL5FZ2Y5U1 / Methotrexate
  • [Number-of-references] 175
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