The distribution of pemphigus vulgaris-IgG subclasses and their reactivity with desmoglein 3 and 1 in pemphigus patients and their first-degree relatives

Background: Pemphigus vulgaris (PV) autoantibodies (PV-IgG) have been found in 40-70% of sera of first-degree relatives of pemphigus patients. Objectives: To determine the possible role of PV-IgG subclasses in the pathogenesis of the disease. Patients and methods: Study groups comprised 25 PV patients, 55 unaffected family members and 56 sera of healthy individuals. Indirect immunofluorescence (IIF) staining and Western immunoblotting (WB) techniques were used to determine total PV-IgG and PV-IgG subclasses and their reactivity to desmoglein (Dsg) 1 and 3. Results: By IIF staining, circulating PV-IgG were found in 64% of the patients, in 15% of the relatives and in none of the controls (P ≤ 0.001); by WB the results were 91%, 49% and 12%, respectively (P ≤ 0.001). The distribution of PV-IgG subclasses 1-3 was similar among patients and their relatives. PV-IgG4 was found in 62% of the patients but in only one relative and was absent in the controls (P ≤ 0.001). PV-IgG1, 2 and 4 were found to react mainly with Dsg3 and PV-IgG3 mainly with Dsg1 and 3. Conclusions: These results support the concept of a genetic predisposition in pemphigus. The non-complement-fixing PV-IgG4 and at least one complement-fixing PV-IgG subclass appear to be involved in the pathogenesis of the disease. The absence of PV-IgG4 among relatives who were PV-IgG carriers seems to be linked to the fact that they do not develop pemphigus. The exact nature of this linkage is still unclear.