Peripheral blood immunoglobulin A level is independently negatively correlated with renal involvement in newly diagnosed childhood systemic lupus erythematosus: a single-center cross-sectional study based on 380 pediatric lupus nephritis patients in southwest China.

backgroundLupus nephritis is a key factor affecting the prognosis of childhood-onset systemic lupus erythematosus (SLE). Immunoglobulin A (IgA) participates in immune regulation through pathways such as mucosal immunity; however, its specific role in pediatric lupus nephritis remains unclear. This study aims to investigate the association between peripheral blood IgA levels and the development of lupus nephritis in children with newly diagnosed SLE.

methodsThis single-center cross-sectional study consecutively enrolled 380 children with newly diagnosed SLE at Kunming Children's Hospital between January 2023 and December 2025. According to the International Classification criteria for pediatric lupus nephritis, using 24-h urinary protein excretion > 0.15 g/24 h as the primary indicator, patients were divided into the lupus nephritis group (n = 238, 62.6%) and the non-lupus nephritis group (n = 142, 37.4%). Binary logistic regression models were used to assess the association between IgA levels (as both a continuous variable and quartile groups) and lupus nephritis, with stepwise adjustment for demographic characteristics, complement levels, autoantibodies, C-reactive protein, and urinary protein. Potential nonlinear relationships were explored using restricted cubic splines, and subgroup analyses were performed according to sex, anti-dsDNA antibody status, anti-nucleosome antibody status, and age.

resultsSerum IgA levels in the lupus nephritis group were significantly lower than those in the non-lupus nephritis group (median: 1.48 vs. 1.87 g/L, P < 0.001). Univariate logistic regression analysis showed that each 1 g/L increase in IgA level was associated with a 40% reduction in the risk of lupus nephritis (OR = 0.60, 95% CI 0.47-0.76, P < 0.001). Quartile analysis of IgA levels revealed a consistent decreasing trend in the proportion of lupus nephritis as IgA levels increased from the lowest to the highest quartile (78.9%, 62.1%, 59.4%, and 50.0%, respectively). In multivariate models, after adjusting for age and sex, the OR was 0.59 (0.46-0.75); with further adjustment for C3 and C4 levels, the OR was 0.61 (0.47-0.79); after adjustment for autoantibodies, the OR was 0.61 (0.47-0.78); and in the fully adjusted model (adjusted for age, sex, C3, C4, CRP, urinary protein, and autoantibodies), the OR was 0.51 (0.36-0.72). All models showed P < 0.001. Restricted cubic spline analysis revealed no nonlinear relationship (P > 0.05). Subgroup analyses indicated that the protective effect of IgA remained consistent across subgroups of sex, anti-dsDNA antibody status, anti-nucleosome antibody status, and age (all P for interaction > 0.05), although a marginal interaction was observed in the low C4 subgroup (P = 0.025).

conclusionAmong children with newly diagnosed systemic lupus erythematosus, peripheral blood IgA level is independently and negatively associated with the presence of lupus nephritis, and this association remains stable across different clinical subgroups. This finding suggests a potential protective role of IgA in the pathogenesis of pediatric lupus nephritis, providing new insights into its immune mechanisms and laying a foundation for future prospective studies. Key Points • Serum IgA is significantly lower in pediatric SLE patients with lupus nephritis. • Each 1 g/L increase in IgA level was associated with a 40% lower odds of having lupus nephritis • The negative association remains independent of complements and autoantibodies. • IgA shows a consistent protective effect across sex and autoantibody subgroups. • IgA may serve as a protective biomarker for renal involvement in childhood SLE.