Figure 2.

Epitope spreading in lupus nephritis. This diagram illustrates the process of epitope spreading in lupus nephritis. Early in the disease, nucleosome–autoantibody complexes form in the mesangium, causing mild kidney damage. As the disease progresses, epitope spreading occurs, leading to the production of additional autoantibodies targeting histone proteins and other glomerular autoantigens, such as snRNP and C1q. This results in immune complex deposition in the subendothelial and subepithelial spaces, contributing to more severe forms of lupus nephritis (Class III/IV). This process not only exacerbates autoimmunity but also contributes to the progression and severity of the diseases, significantly contributing to the heterogeneity and severity of renal involvement in lupus patients. Furthermore, kidney tertiary lymphoid structures (TLSs) can promote a localized immune response against specific autoantigens overexpressed in the inflamed tissue, in association with epitope spreading, higher disease activity, and poor treatment response. (Created in BioRender.com).