IgG subclasses and their significance in pemphigus disease progression monitoring

Immunoglobulin G (IgG) subclasses have been documented to have a close association with pemphigus. Nevertheless, the relationship among IgG subclasses, anti-desmoglein (anti-Dsg) autoantibodies, and disease activity remains ambiguous, and their potential utility in monitoring disease progression has yet to be fully clarified.

This study aims to unravel the associations among IgG subclasses, autoantibodies, and disease activity, thereby offering specific serological evidence to facilitate accurate disease assessment.

Confirmed pemphigus patients (n=183) and healthy controls (n=38) were enrolled. Chemiluminescent immunoassay (CLIA) was used to measure serum levels of IgG1, IgG2, IgG3 and IgG4 in all participants. For pemphigus patients, the levels of anti-Dsg1 and Dsg3 autoantibodies were detected using enzyme-linked immunosorbent assay (ELISA). The correlations of IgG subclasses with anti-Dsg1 and Dsg3 autoantibodies, and pemphigus disease area index (PDAI) were evaluated in different disease stages.

Overall, pemphigus patients showed significantly lower levels of IgG3 and IgG4 (P = 0.022 and P = 0.040, respectively) compared with healthy controls. IgG subclasses exhibited a notable correlation with autoantibody levels, particularly during treatment. In patients with single positivity for anti-Dsg1, all IgG subclasses were lower in the remission group than in the healthy controls and active group. In contrast, among patients with double positivity for anti-Dsg1/3, IgG3 levels were significantly lower in the remission group. In patients with single positivity for anti-Dsg3, IgG2 levels differed markedly between the active group and the other groups. Receiver operating characteristic (ROC) curve identified an IgG2 cutoff of 5224 (AUC = 0.7277) for anti-Dsg3 single-positive patients and an IgG3 cutoff of 189 (AUC = 0.7596) for anti-Dsg1/Dsg3 double-positive patients to distinguish active and remission pemphigus.

IgG2 and IgG3 may serve as valuable adjunctive markers to existing assays for Dsg antibodies. Detection of IgG2 and IgG3 could serve as effective serological tools for judging disease status and facilitating individualized clinical assessment.