Immune Responses Associated With Nephritis-Associated Plasmin Receptor in IgA Vasculitis

IgA vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is a small-vessel vasculitis characterized by IgA-dominant immune deposits in the skin, kidney, gastrointestinal tract, and joints, often following infections, particularly β-hemolytic streptococci. Nephritis-associated plasmin receptor (NAPlr), a streptococcal glyceraldehyde-3-phosphate dehydrogenase, has been identified as a nephritogenic protein in post-streptococcal acute glomerulonephritis, binding plasmin and maintaining its proteolytic activity, thereby promoting tissue injury. However, the role of NAPlr in IgAV pathophysiology remains unclear. In this study, we investigated histological staining for NAPlr and plasmin activity in IgAV cutaneous lesions and evaluated circulating anti-NAPlr antibodies. Skin specimens from patients with IgAV were analyzed by immunofluorescence and in situ zymography, and serum anti-NAPlr antibodies (IgG, IgM, and IgA) were measured by enzyme-linked immunosorbent assay in 21 patients with IgAV and 18 healthy donors. Positive staining for NAPlr and plasmin activity was observed in dermal lesions in 7 of 11 patients with IgAV, but was minimal in control skin. Patients with IgAV showed significantly elevated serum levels of anti-NAPlr IgG and IgA antibodies compared with healthy donors. Anti-NAPlr IgG levels positively correlated with serum creatinine and negatively correlated with CH50, with a nonsignificant inverse association with estimated glomerular filtration rate (eGFR). Serum galactose-deficient IgA1 levels were also significantly increased in patients with IgAV, and were positively correlated with anti-NAPlr IgA levels but negatively correlated with C4. These findings demonstrate the presence of a protein that is stained by anti-NAPlr antibody in IgAV cutaneous lesions alongside elevated circulating anti-NAPlr antibodies, suggesting that immune responses to NAPlr may contribute to IgA-mediated vascular inflammation, potentially through complement activation.