[Mutation of nuclear autoantigenic sperm protein (NASP) gene aggravates autoimmune response in induced lupus model...

Objective To prepare inducible lupus model mice and investigate the effect of nuclear autoantigenic sperm protein (NASP) gene mutation on the autoimmune response of mice with induced systemic lupus erythematosus (SLE). Methods The 3-month wild-type B6 (B6-WT) mice were used as a control group and the NASP mutant B6 (B6-NASP^M) mice as an experimental group. Mouse spleen lymphocytes were activated with concanavalin A (ConA), and the DNA was extracted as autoantigen. B6-WT mice and B6-NASP^M mice were immunized three times. Serum anti-double stranded DNA (dsDNA) IgG levels were detected by ELISA. Renal lesions were detected by HE staining. Immunohistochemical staining was performed to detect the deposition of IgG and complement C3 in the renal tissues. Flow cytometry was applied to compare the spleen lymphocyte subsets in B6-WT and B6-NASP^M mice and to explore the mechanism of NASP gene mutation affecting the immune response in mice. Results Compared with B6-WT mice, B6-NASP^M mice showed no significant changes in body weight, kidney index and spleen index; serum anti-dsDNA IgG levels significantly increased; glomerular cell proliferation was obvious and the deposition of IgG and C3 in the renal tissues increased. The proportion of spleen CD3⁺ T cells and natural killer (NK) cells decreased, while the proportion of CD19⁺ B cells and regulatory B cells (Breg) increased. Conclusion Mutation in the NASP gene can increase the levels of anti-dsDNA IgG antibodies, promote cell proliferation in the glomerulus of the kidney, deposition of IgG antibodies and complement C3, alter the proportion of immune cells in the spleen and aggravate the autoimmune response in lupus model mice.