The severity of cutaneous and oral pemphigus is related to desmoglein 1 and 3 antibody levels

Background Pemphigus vulgaris (PV) and foliaceus (PF) are characterized by antibodies to the desmosomal proteins desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1), respectively. Past studies using indirect immunofluorescence (IIF) as a measure of pemphigus antibody levels have failed to demonstrate consis tently a relationship between disease severity and IIF titres. However, IIF is not able to measure separately Dsg1 and 3 antibodies, unlike enzyme-lin ked immunosorbent assays (ELISA), which utilize recombinant proteins. Objectives To compare independently Dsg1 and 3 antibody levels with the sev erity of both cutaneous and oral involvement in PV and PE Patients and methods Four hundred and twenty-four serum samples were analys ed from 80 subjects with PV and 24 with PE IgG antibodies to Dsg1 and 3 wer e measured by ELISA, For every sample analysed, the associated severity of skin and oral disease were graded from 0 to 3; quiescent, mild, moderate an d severe. Results A relationship between Dsg1 antibodies and skin severity was demons trated such that a 10-unit increase in Dsg1 ELISA value was associated with a 34% chance of having a higher severity score [95% confidence interval (C I), 25-45%, P < 0.0005]. This was observed in both PV and PE Oral severity was associated with Dsg3 antibody levels and a 10-unit increase in the Dsg3 ELISA value was associated with a 25% chance of a higher oral severity sco re (CT 17-33%, P < 0.0005). We were unable to demonstrate a relationship be tween Dsg1 antibodies and oral severity, even after adjusting for the effec t of Dsg3 antibodies, Similarly, there was no relationship between Dsg3 ant ibodies and skin severity, Conclusions This study suggests that the clinical phenotype of pemphigus, i n particular the balance of skin and oral disease, is determined principall y by the quantities of Dsg1 and 3 autoantibodies, respectively.