Effects Of Anti-CD6Monoclonal Antibody Itolizumab On Cd4+T Lymphocytes Of Patients With Lupus Nephritis

Background:T lymphocytes play an important role in the pathogenesis process of systemic lupus eryhtematosus (SLE). The quantitative and qualitative deficiencies of Treg are the major characteristic in patients with SLE. Itolizumab (T1h) is a novel humanized anti-CD6monoclonal antibody, showed a therapeutic immunosuppressive function in rheumatoid arthritis and psoriasis patients clinical trials. The immunosuppressive function of Tlh depends on inhibition of T cell activation and proliferation by binding with CD6molecules on the surface of CD4+T lymphocytes without inhibiting CD6CD166interaction.Objective:To investigate phenotypic characteristic of CD4+T lymphocytes in patients with SLE. To assess the effects of T1h on D4+T lymphocytes of patients with lupus nephritis.Methods:PBMC of10new-onset SLE (nSLE) patients,6post-therapeutic SLE (pSLE) patients and10health control were analyzed for the expression of CD4, CD6and CD25on PBMC and expression of CD6on both effector T cells and regulatory T cells by flow cytometry. We also estimate the correlation between expression profile and clinical data. PBMC of4post-therapeutic SLE patients with lupus nephritis and4health control were cultured with Oμg/ml,2.5μg/ml,10μg/ml and40μg/ml T1h for24hours and72hours respectively, analyzed for the expression of CD4, CD25, CD69and FoxP3using flow cytometry.Results:(1) In nSLE patients, the expression of CD6among CD4+cells was higher than health control (94.08%±3.01%vs89.03%±6.37%, P<0.05).(2) The frequency of CD4+CD25high cells were lower in pSLE patients than health control (0.103%±0.115%vs0.339%±0.149%, P<0.05). The CD4+CD25-cells of nSLE patients express higher level of CD6than pSLE patients (P=0.011). The CD4+CD25high cells of nSLE patients and health control express higher level of CD6than pSLE patients (P=0.001,0.003).(3) The difference of CD6, CD25expression level on CD4+cells were not significant between nSLE-LN patients and pSLE-LN patients.(4) The frequency of CD6among CD4+cells showed no significant correlation with24hour urine protein level, serum complementary3and complementary4levels, serum anti-ds-DNA antibody titers and SLE disease activity in nSLE patients.(5) The proportion of Treg cells elevated and function of Treg cells regained with the rising concentration of T1h. T1h had no significant effect on effector T cells.Conclusion:The elevated CD6frequency among CD4+cells may play an important role in pathogenesis of SLE-LN. In LN patients, Tlh could increase the level of CD4+CD25highFoxP3+regulatory T cells and modify the abnormal Treg to regain immunosuppressive function.