The immunoglobulin G subclass distribution of anti-GBM autoantibodies against rHalpha3(IV)NC1 is associated with disease severity.

The current study aimed to investigate the association between antiglomerular basement membrane (GBM) immunoglobulin (Ig) G subclass distribution and the severity of anti-GBM nephritis in human beings. Natural anti-GBM IgG affinity purified from five healthy donors was defined as group A. A total of 73 Chinese patients with anti-GBM disease were divided into three groups (groups B, C, and D) according to their serum creatinine (Scr) on diagnosis. Anti-GBM IgG subclasses were detected by enzyme-linked immunosorbent assay using recombinant human noncollagenous domain 1 of type IV collagen of the alpha3 chain [rHalpha3(IV)NC1]. Anti-GBM IgG1 could not be detected in group A (0%), appeared in group B (7.7%), was significantly higher in group C (69%), and was the highest in group D (93.5%). The frequency of IgG3 in groups C and D was significantly higher than that in groups A and B. In group A, anti-GBM IgG subclass distribution was restricted to IgG4 and IgG2; in group B, IgG2 and IgG4 remained the major subclasses with detectable IgG1; in group C, IgG1 became predominant and IgG3 was detectable; in group D, four IgG subclasses could be detected. In conclusion, anti-GBM autoantibody IgG subclass distribution was associated with disease severity. IgG1 and IgG3 may play a major role in the initiation and progression of the disease.