Anti-Desmoglein 3 Avidity Correlates Better With Pemphigus Vulgaris Severity Than Anti-Desmoglein 3 Concentration

Pemphigus vulgaris (PV) is caused by immunoglobulin G (IgG) autoantibodies targeting desmoglein 3 (Dsg3) and/or desmoglein 1 (Dsg1). While antibody concentration is routinely used to assess disease activity, the role of antibody avidity in PV monitoring has not been elucidated.

Sixty-three consecutive, newly diagnosed, treatment-naïve patients with PV were enrolled in this retrospective-prospective study. PV severity was assessed using the Pemphigus Disease Area Index (PDAI) and classified as mild (≤ 15), moderate (> 15, ≤ 45), or severe (> 45). Anti-Dsg3 and anti-Dsg1 IgG antibodies' concentration and avidity were determined using conventional and urea-modified enzyme-linked immunosorbent assay (ELISA), respectively. Thirty-three patients were re-evaluated at the beginning of clinical remission. Receiver operating characteristic (ROC) curve analyses were used to determine optimal cut-off values and odds ratios (ORs) for anti-Dsg3 concentration and avidity to distinguish active disease from remission, and mild from moderate-to-severe disease.

Anti-Dsg3 avidity showed a stronger correlation with PDAI (r = 0.474, p < 0.001) than anti-Dsg3 concentration (r = 0.363, p = 0.004). Anti-Dsg1 concentration correlated with PDAI (r = 0.476, p = 0.001), while anti-Dsg1 avidity did not (r = 0.216, p = 0.141). Anti-Dsg3 avidity was a better marker of disease severity than anti-Dsg3 concentration (p = 0.003 vs. p = 0.014). Among 13 patients in remission who were still anti-Dsg3-positive, avidity decreased more significantly than concentration (p = 0.007 vs. p = 0.016). Avidity cut-off of 25.46% distinguished active disease from remission (OR = 3.48), and avidity 35.02% threshold differentiated mild from moderate/severe disease (OR = 6.36).

This is the first study to assess the correlation between PDAI and anti-Dsg3/anti-Dsg1 avidity. Anti-Dsg3 avidity showed the strongest positive correlation with PDAI, announcing the role of antibody avidity as a valuable biomarker in monitoring PV activity.