Role of autoantibodies to various Ro60 epitopes in the decrease of lymphocytes seen in systemic lupus erythematosus and primary Sjögren's syndrome.

We investigated the roles of autoantibodies to different Ro60 epitopes in lymphopenia in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). We recruited 16 patients with SLE, 14 with pSS, and 10 healthy controls; all were female. Patients had active disease, had not received glucocorticoid or immunosuppressants for at least 3 months, and had positive laboratory tests for autoantibodies against Ro60. Patient peripheral blood lymphocyte (LC) counts were < 1 x 10(9)/L: (0.66 ± 0.12) x 10(9)/L and (0.70 ± 0.16) x 10(9)/L for SLE and pSS groups, respectively (P = 0.511). LCs from each group were cultured in vitro with each of the three immunotoxins (ITs) (AE1-3), which specifically combine with one of the three epitopes (aa482-493, aa310-323, and aa230-241, respectively) on Ro60. The cytotoxicity of each IT to the cultured LCs was measured by the MTT colorimetric method. The relationships between IT cytotoxicity and LC counts were analyzed, and autoantibodies against the three epitopes in patient peripheral blood were detected. All ITs showed cytotoxicity to control LCs; however, AE3 and AE2 showed greater toxicity to LCs from SLE and pSS groups, respectively, and the enhanced cytotoxicity was significantly associated with the respective LC counts (r = 0.653, P = 0.06; r = 0.594, P = 0.025). No difference was found in the prevalence of the autoantibodies between the SLE and pSS groups. These results suggest that autoantibodies to Ro60 might play a pathogenic role in lymphopenia in both SLE and pSS, but the pathogenic mechanisms might differ.