Background and objectives The reason why mesangial C4d deposits are detected in only certain biopsies of IgA nephropathy remains unclear. We analyse the association between IgA glycosylation patterns, mesangial C4 deposition and clinical phenotypes in IgA nephropathy. Design, setting, participants and measurements: This cross-sectional study included 145 patients with idiopathic IgA nephropathy. We measured the serum levels of three different IgA1 lectin-binding specificities, using enzyme-linked-immunosorbent assays with and without treatment with neuraminidase, and we analysed the relationship between these glycoforms, C4d mesangial deposits and clinical phenotypes. Results C4d-positive vs Cd4-negative patients had higher proteinuria (median: 3.1 g/g [0.9-4.2] vs. 1.8 g/g [1-2.2]; p = 0.000), hematuria (223 cel/µL [32-278] vs 99 cel/µL [25-186], p = 0.000), and higher levels of IgA binding to neuraminidase untreated Helix Aspersa (HA IgA1 neu-) (150.6 ± 52 U vs 96.2 ± 64.1 U, p = 0.000), neuraminidase untreated Helix Pomatia (HPA IgA1 neu-) (0.34 ± 0.15 vs 0.27 ± 0.13p = 0.04), Triticum vulgaris (TV IgA1) (85.1 ± 31.7 vs42.2 ± 26.9p = 0.000), and Canavalia ensiformis (ConA IgA1) (32.5 ± 18 U vs 16.7 ± 9.38 U, p = 0.000). The levels of HA IgA1 neu-, HPA IgA1 neu-, TV IgA1 and ConA IgA1 were all associated with the mesangial deposition of C4d, extracapillary proliferation and acute kidney injury. In ROC curves, HA IgA1 neu-, HPA IgA1 neu-, TV IgA1 and ConA IgA1 significantly discriminated between C4d positive ad C4d-negative biopsies. In logistic models, TVIgA1 and ConAIgA1 were the only independent predictors of mesangial C4d deposits. Conclusions In IgA nephropathy, the severity of the disease is associated with the level of IgA exposing N-Acetyl-D-Galactosamine, N-Acetyl-D-Glucosamine or mannose whereas C4d deposits are only associated with elevated levels of IgA1 glycoforms exhibiting glycan residues with specificity for mannose and N-Acetyl-D-Glucosamine binding lectins.

No abstract