`Integrated multi-modal dissection of IVIg-mediated immune reprogramming in lupus mice

Intravenous immunoglobulin (IVIg) is widely used to treat autoimmune diseases, yet its precise mechanisms of action in systemic lupus erythematosus remain incompletely understood. Here, we employed an integrated multi-modal approach combining single-cell RNA sequencing, quantitative proteomics, flow cytometry, immunofluorescence, enzyme-linked immunosorbent assay, and histopathological analysis to investigate IVIg-induced immune reprogramming in MRL/lpr lupus-prone mice. IVIg treatment markedly alleviated disease manifestations, including splenomegaly, proteinuria, renal injury, and systemic autoantibody production. Histological examination of the spleen and kidney showed decreased lymphoid hyperplasia, glomerular inflammation, and tissue damage in IVIg-treated mice. At the immune-cell level, IVIg was associated with alterations in T and B cell activation states, partial restoration of immune repertoire diversity, and shifts in dendritic cell populations. Collectively, our integrated analyses suggest that IVIg treatment is correlated with broad immunomodulatory changes in splenic immune composition in lupus-prone mice.