LYMPHOPROLIFERATION IN PRIMARY SJOGRENS-SYNDROME - EVIDENCE OF SELECTIVE EXPANSION OF A B-CELL SUBSET CHARACTERIZED BY THE EXPRESSION OF CROSS-REACTIVE IDIOTYPES

Objective. To evaluate the possibility that lymphoproliferation in pri mary Sjogren's syndrome (SS) arises within a subset of B cells. Method s. A panel of monoclonal antibodies (MAb) specific for rheumatoid fact or (RF)-associated cross-reactive idiotypes (CRI) and anti-V(kappa) an d anti-V(H) subgroup antibodies were used to define the clonality of B lymphocytes undergoing neoplastic transformation in 5 patients with p rimary SS. Anti-CRI antibodies were also used to study longitudinal va riations in serum paraprotein levels and in vitro regulation of IgM an d IgM-RF production by peripheral blood lymphocytes. The levels of CRI , IgM, and IgM-RF were quantitated in serum and culture supernatants b y enzyme-linked immunosorbent assay. Heavy and light chain isotypes an d V(H) subgroups of the paraproteins were determined by immunoelectrop horesis, immunofixation, and Western blotting. Results. Paraproteins f rom all patients expressed an epitope associated with V(kappa)IIIb sub -subgroup of light chains. Three of the paraproteins were cryoglobulin s with RF activity, all of which expressed the V(kappa)IIIb-associated CRI (detected by MAb 17-109) and the V(H)I-associated CRI (detected b y MAb G6 and G8). None of the paraproteins expressed the V(H)III-assoc iated CRI (detected by MAb B6 and D12). The CRI were consistently expr essed over a period of 5-6 years. The anti-CRI and anti-subgroup antib odies substantially inhibited spontaneous production of IgM-RF and IgM by peripheral blood B lymphocytes from 3 of the SS patients. Conclusi on. These results suggest that lymphoproliferation in primary SS is hi ghly selective, and that the anti-CRI antibodies can be used as an aid to early diagnosis as well as for monitoring and modulating the lymph oproliferative process in primary SS.