Expression of a cross-reactive idiotype on rheumatoid factor in patients with Sjogren's syndrome.
Primary Sjogren's syndrome (SS) is a systemic autoimmune disorder characterized by lymphocytic infiltration of salivary and lacrimal glands. These patients have evidence of marked B cell hyperactivity, including the production of autoantibodies such as rheumatoid factor (RF) and an increased frequency of non-Hodgkin's lymphoma. We now demonstrate that RF from 12/15 SS patients contains a cross-reactive idiotype (CRI) on their kappa light chain defined by a monoclonal antibody (MoAb 17-109) and immunoblotting. This CRI was associated with immunoglobulin (Ig) A-RF, and to a lesser extent with IgM-RF molecules on the basis of direct binding studies. With the use of immunoperoxidase techniques to stain frozen tissue sections, B cells containing cytoplasmic Ig reactive with MoAb 17-109 were detected in the salivary gland biopsies from 11/12 SS patients at high frequencies, and in the blood from the same patients at much lower frequencies. One patient with pre-existant SS developed non-Hodgkin's lymphoma with tumor cells and RF paraprotein reactive with MoAb 17-109. Evaluation of serial biopsies over a 4-yr period showed a progressive increase in the proportion of B cells bearing the CRI. In contrast, synovial membrane biopsies from RA patients lacking sicca symptoms did not contain B cells expressing the CRI. Because previous studies have demonstrated that MoAb 17-109 detects a CRI on RF paraproteins from patients with lymphoma, B cells bearing this CRI may have increased frequency of neoplastic transformation. SS patients provide an opportunity to study the expression of this CRI and to understand the transition of B cell clones from autoimmune proliferation to neoplastic transformation.
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D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D003429:Cross Reactions; D005260:Female; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000032:analysis; D007130:Immunoglobulin Idiotypes / Q000032:analysis* / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D008214:Lymphocytes / Q000145:classification / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000032:analysis* / Q000096:biosynthesis / Q000276:immunology; D012469:Salivary Glands / Q000166:cytology; D012859:Sjogren's Syndrome / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007126:Immunoglobulin Allotypes; D007130:Immunoglobulin Idiotypes; D007145:Immunoglobulin kappa-Chains; D012217:Rheumatoid Factor