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Objective: To investigate IgDs biological function and regulation in RA patients, we accessed the expression of secretory IgD and membrane IgD on RA and healthy control, and meanwhile observed the influence of secretory IgD on lymphocytes proliferation, phenotypic expression and IgD receptor expression in human peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis(RA) and healthy controls.Methods: Blood samples were obtained from 54 RA patients and 30 healthy donors, PBMCs were separated by ficoll gradient centrifugation.The frequency and distribution of IgD in T and B cell subsets in the peripheral blood of active RA patients with long-standing disease had been analyzed.Additionally, PBMCs from RA patients were treated with different concentrations of human IgD protein.PBMCs proliferation, IgDR expression, T/B cell subsets and inflammatory cytokines production were assessed.Results: The level of sIgD in serum of RA patients was higher than healthy control.There was very little mIgD expressed on human T cells, the level of expression of mIgD and IgDR on each peripheral blood T and B cell subsets was higher in the RA patients than healthy control.In RA patients samples, it was found that IgD induced PBMCs proliferation in vitro; obviously increased the percentage of CD3+IgDR+T cells, CD3+CD4+IgDR+T cells and CD19+IgDR+B cells; increased the percentage of CD4+CD69+, CD4+CD 154+, CD 19+CD23+, CD 19+CD21 +, CD 19+IgD+ and CD 19-CD 138+; at mean while decreased CD3+CD8+, CD4+CD62L and CD19+IgM+IgD-in PBMCs.Furthermore, inflammatory cytokines levels such as IL-1 α, IL-1 β, TNF-α, IL-6, and IL-10 in cultured PBMCs supernatant were increased by IgD.Conclusion: Our data indicate that IgD play important role in RA patients, which involves high expression of sIgD and mIgD.Secreted IgD binds to T and B cells, induces its own receptor, stimulates proliferation, activation, and differentiation of lymphocytes, and induces cytokine production, which demonstrates that IgD has immunoaugmenting and pro-inflammatory properties.IgD and IgDR represent potentially new immunotherapeutic targets for autoimmune diseases such as RA that involve abnormal level of sIgD and mIgD.