Lymphomas complicating Sjogren's syndrome and hepatitis C virus infection may share a common pathogenesis: chronic stimulation of rheumatoid factor Bcells

Background-The occurrence of B cell non-Hodgkin's lymphoma is a complicatio n of Sjogren's syndrome (SS) and, at least in some countries, of chronic he patitis C virus (HCV) infection. Lymphomas occurring in both diseases share a number of characteristics: predominance of low grade, marginal zone hist ological type, frequency of mucosal. localisation, possible transformation into a large B cell lymphoma, association with asymptomatic low level cryog lobulinaemia, absence of virus within lymphoma cells, but localisation of l ymphomas in organs where the chronic viral infection is active in patients with HCV and where the autoimmune disease is active in patients with SS. Hypothesis-It is proposed that in both diseases the first event of lymphoma -genesis is the chronic stimulation at the site of the disease of polyclona l B cells secreting rheumatoid factor (RF). Then, that these RF B cells may become monoclonal and disseminate in other organs. The monoclonal secreted RF complexed with polyclonal IgG may cryoprecipitate. The following step w ould be a chromosomal abnormality (for example, trisomy 3 or bcl-2 transloc ation) which would confer to these cells a low grade B cell lymphoma. compo rtment. A last event (for example, a mutation of p53) might transform this low grade B cell lymphoma. into a high grade, large B cell lymphoma. The no n-random utilisation of VH and VL by SS associated lymphoma. B cells and th e recent demonstration that these lymphoma B cells may display RF activity support the hypothesis that these lymphomas grow through an autoantigen dri ven process. Conclusion-The best preventive treatment of lymphoproliferations occurring in SS probably consists in decreasing the hyperactivation of autoreactive B cells when it is present, allowing the use of immunosuppressive drugs such as methotrexate or even tumour necrosis factor a antagonists, which in the ory could favour other types of lymphoproliferation.