ABSTRACT
Pemphigus vulgaris (PV) is associated with autoantibodies against desmoglein (Dsg) 3 inducing epidermal loss of adhesion. The major pathogenic epitopes of Dsg3 are presumably dependent of their conformation. The aim of this study was to characterize the IgG reactivity of sera from a cohort of clinically well-characterized PV patients against presumably non-conformational subdomains of the Dsg3 ectodomain including recently described NH2-terminal immunodominant epitopes. By ELISA, IgG reactivity against distinct subdomains of Dsg3 was related to disease activity and the clinical phenotype of PV patients. Our findings suggest that (i) autoantibody from PV sera react with non-conformational epitopes of Dsg3; (ii) IgG reactivity against the NH2-terminus and the extracellular domains (EC) 2-4 of Dsg3 was associated with active PV, while IgG titres were not strictly correlated with disease activity and (iii) IgG reactivity against the EC1-4 was associated with mucosal dominant PV and was decreased in cutaneous dominant PV. The findings may help to define more refined serological disease markers of PV.
Subject(s)
Desmoglein 3/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Pemphigus/immunology , Pemphigus/pathology , Autoantibodies/immunology , Autoimmunity/immunology , Biomarkers/blood , Case-Control Studies , Desmoglein 3/chemistry , Epitopes/chemistry , Epitopes/immunology , Humans , Pemphigus/blood , Phenotype , Protein Conformation , Protein Structure, TertiaryABSTRACT
Pemphigus vulgaris (PV) is an autoimmune disease caused by immunoglobulin G (IgG) autoantibodies against the desmosomal adhesion molecules, desmoglein (Dsg)3 and Dsg1. The aim of the study was to relate IgG reactivity of 123 PV sera and 40 control sera against NH(2)-terminal non-conformational epitopes of Dsg3 and Dsg1 with disease activity and clinical phenotype by enzyme-linked immunosorbent assay. The results show that (i) the overall reactivity and the titres of IgG reactive with the Dsg3 ectodomain, Dsg3(1-566), significantly correlated with the disease activity of the PV patients; (ii) IgG reactivity against the NH(2)-terminus of Dsg3, Dsg3(1-161), was associated with active PV while there was no direct correlation between the IgG titres and the disease activity; (iii) IgG reactivity against the NH(2)-terminus of Dsg3, Dsg3(1-161), was associated with mucosal and mucocutaneous PV; (iv) IgG titres against a small stretch of the NH(2)-terminus of Dsg3, Dsg3(25-88), were associated with active PV; and (v) IgG in the PV sera detected non-conformational epitopes in addition to the previously identified conformation-dependent epitopes of the Dsg3 and Dsg1 ectodomains.
