Pemphigus vulgaris disease activity: The role of antibodies to desmogleins and their isotype

Background Pemphigus vulgaris (PV) is an autoimmune blistering disease driven by pathogenic antibodies to desmoglein-1 and -3, levels of which correlate with disease activity. Anti-desmoglein-3 IgG4 isotype antibodies are said to predominate in active disease and anti-desmoglein-3 IgG1 in remission; however, these observations arose from vertical studies, with limited assessments of clinical activity. The objective of this study was to examine the relationship between desmoglein autoantibodies, subdivided by isotype and disease activity using the validated PV activity tool "Pemphigus Disease Area Index (PDAI)." Methods Forty PV patients with predominantly mucosal disease were studied prospectively, 24 serially, and PDAI and anti-desmoglein antibodies recorded at each visit over a period of up to 15 months. Results At enrolment, only anti-desmoglein-3 IgG4 levels were significantly associated with disease activity but the correlation was weak. During follow-up, within-patient changes in disease activity correlated with changes in anti-desmoglein-3 IgG levels, but correlations were similar for both anti-desmoglein-3 IgG1 and IgG4. These trends were not observed in anti-desmoglein-1 IgG levels, although the majority of patients were negative at baseline. Conclusions Anti-desmoglein-3 IgG4 levels correlated only weakly with PDAI scores at a single time point. Reciprocity of IgG1 vs IgG4 anti-desmoglein-3 with changes in disease activity over time could not be confirmed, but rather, changes in levels of anti-desmoglein-3 IgG, irrespective of isotype, were useful in following individual patient responses.