Lymphoproliferation in primary sjögren's syndrome. evidence of selective expansion of a b cell subset characterized by the expression of cross‐reactive idiotypes

Abstract

Objective. To evaluate the possibility that lymphoproliferation in primary Sjögren's syndrome (SS) arises within a subset of B cells. Methods. A panel of monoclonal antibodies (MAb) specific for rheumatoid factor (RF)–associated cross-reactive idiotypes (CRI) and anti-V_K and anti-V_H subgroup antibodies were used to define the clonality of B lymphocytes undergoing neoplastic transformation in 5 patients with primary SS. Anti-CRI antibodies were also used to study longitudinal variations in serum paraprotein levels and in vitro regulation of IgM and IgM-RF production by peripheral blood lymphocytes. The levels of CRI, IgM, and IgM-RF were quantitated in serum and culture supernatants by enzyme-linked immunosorbent assay. Heavy and light chain isotypes and V_H subgroups of the paraproteins were determined by immunoelectrophoresis, immunofixation, and Western blotting. Results. Paraproteins from all patients expressed an epitope associated with V_KIIIb sub-subgroup of light chains. Three of the paraproteins were cryoglobulins with RF activity, all of which expressed the V_KIIIb-associated CRI (detected by MAb 17–109) and the V_HI-associated CRI (detected by MAb G6 and G8). None of the paraproteins expressed the V_HIII-associated CRI (detected by MAb B6 and D12). The CRI were consistently expressed over a period of 5–6 years. The anti-CRI and anti-subgroup antibodies substantially inhibited spontaneous production of IgM-RF and IgM by peripheral blood B lymphocytes from 3 of the SS patients. Conclusion. These results suggest that lymphoproliferation in primary SS is highly selective, and that the anti-CRI antibodies can be used as an aid to early diagnosis as well as for monitoring and modulating the lymphoproliferative process in primary SS.