Origin of B-Cell Neoplasms in Autoimmune Disease

• Published in: PloS one 2016-06, Vol.11 (6), p.e0158360
• Main Authors: Hemminki, Kari, Liu, Xiangdong, Ji, Jianguang, Försti, Asta
• Format: Article
• Language: English
• Subjects: Arthritis; Autoimmune diseases; Autoimmune Diseases - genetics; Autoimmune Diseases - pathology; B cells; B-cell lymphoma; B-Lymphocytes - pathology; Biology and Life Sciences; Cancer; Carcinogens; Cell division; Chronic lymphocytic leukemia; Class switching; Clinical Medicine; Dermatomyositis; Disease control; Epidemiology; Female; Follow-Up Studies; Genetic transformation; Germinal Center - pathology; Health risk assessment; Hodgkin Disease - pathology; Hodgkin's disease; Hodgkin's lymphoma; Humans; Immunology; Klinisk medicin; Leukemia; Lymphatic leukemia; Lymphocytes B; Lymphoma; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - pathology; Lymphoma, Follicular - pathology; Male; Mantle cell lymphoma; Medical and Health Sciences; Medical research; Medicin och hälsovetenskap; Medicine and Health Sciences; Multiple myeloma; Myeloma; Neoplasms; Pathogenesis; Physiological aspects; Polymyositis; Primary care; Purpura; Recombination; Registries; Reumatologi och inflammation; Rheumatoid arthritis; Rheumatology and Autoimmunity; Risk factors; Sjogren's syndrome; Somatic hypermutation; Studies; Systemic lupus erythematosus; Thrombocytopenic purpura; Transformation; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0158360

Autoimmune diseases (ADs) are associated with a number of B-cell neoplasms but the associations are selective in regard to the type of neoplasm and the conferred risks are variable. So far no mechanistic bases for these differential associations have been demonstrated. We speculate that developmental origin of B-cells might propose a mechanistic rationale for their carcinogenic response to autoimmune stimuli and tested the hypothesis on our previous studies on the risks of B-cell neoplasms after any of 33 ADs. We found that predominantly germinal center (GC)-derived B-cells showed multiple associations with ADs: diffuse large B cell lymphoma associated with 15 ADs, follicular lymphoma with 7 ADs and Hodgkin lymphoma with 11 ADs. Notably, these neoplasms shared significant associations with 5 ADs (immune thrombocytopenic purpura, polymyositis/dermatomyositis, rheumatoid arthritis, Sjogren syndrome and systemic lupus erythematosis). By contrast, primarily non-GC neoplasms, acute lymphocytic leukemia, chronic lymphocytic leukemia and myeloma associated with 2 ADs only and mantle cell lymphoma with 1 AD. None of the neoplasms shared associated ADs. These data may suggest that autoimmune stimulation critically interferes with the rapid cell division, somatic hypermutation, class switch recombination and immunological selection of maturing B-cell in the GC and delivers damage contributing to transformation.