title: Origin of B-Cell Neoplasms in Autoimmune Disease.
abstract: 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.
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120, Heidelberg, Germany.|Center for Primary Health Care Research, Lund University, 205 02, Malmö, Sweden.
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.affiliation: Center for Primary Health Care Research, Lund University, 205 02, Malmö, Sweden.|Department of Measles, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Center for Primary Health Care Research, Lund University, 205 02, Malmö, Sweden.
authors.forename: Jianguang
authors.initials: J
authors.lastname: Ji
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120, Heidelberg, Germany.|Center for Primary Health Care Research, Lund University, 205 02, Malmö, Sweden.
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics* / Q000473:pathology; D001402:B-Lymphocytes / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D018858:Germinal Center / Q000473:pathology*; D006689:Hodgkin Disease / Q000473:pathology; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology; D008224:Lymphoma, Follicular / Q000473:pathology; D008297:Male; D012042:Registries