title: Increased oxidative stress in pemphigus vulgaris is related to disease activity and HLA-association.
abstract: Pemphigus vulgaris (PV) is a rare blistering skin disorder characterized by the disadhesion of keratinocytes due to autoantibody attack against epidermal targets including desmoglein (Dsg) 3, Dsg 1 and possibly other adhesion and non-adhesion molecules. The mechanisms leading to immune-mediated pathology in PV are multifactorial and not fully understood. Recently, oxidative stress (antioxidant/oxidant disequilibrium) has been proposed as a contributory mechanism of autoimmune skin diseases, including PV. In this study, we directly assessed oxidative stress via measurement of total antioxidant capacity (TAC) using ELISA in 47 PV patients, 25 healthy controls and 18 bullous pemphigoid (BP) patients. We also performed microarray gene expression analysis on a separate set of 21 PV patients and 10 healthy controls to evaluate transcriptional dysregulation in oxidative stress-related pathways. Our data indicate that there is a significant reduction in TAC levels in PV patients compared with healthy controls, as well as BP patients. Furthermore, PV patients with active disease have significantly lower TAC levels than PV patients in remission. We also find that HLA allele status has a significant influence on oxidative stress. These findings are corroborated by microarray analysis showing differentially expressed genes involved in oxidative stress between the aforementioned groups. Collectively, our findings provide support for a role of oxidative stress in PV. Whether increased oxidative stress leads to disease manifestation and/or activity, or if disease activity leads to increased oxidative stress remains unknown. Future longitudinal studies may help to further elucidate the relationship between PV and oxidative stress.
authors.affiliation: a Department of Dermatology , Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo , NY , USA.
authors.forename: Amit Aakash
authors.initials: AA
authors.lastname: Shah
authors.affiliation: a Department of Dermatology , Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo , NY , USA.
authors.forename: Rama
authors.initials: R
authors.lastname: Dey-Rao
authors.affiliation: a Department of Dermatology , Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo , NY , USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Seiffert-Sinha
authors.affiliation: a Department of Dermatology , Jacobs School of Medicine and Biomedical Sciences, University at Buffalo , Buffalo , NY , USA.
authors.forename: Animesh A
authors.initials: AA
authors.lastname: Sinha
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000975:Antioxidants / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D016022:Case-Control Studies; D051182:Desmogleins / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010392:Pemphigus / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D012720:Severity of Illness Index; D012737:Sex Factors
chemical_list: D000975:Antioxidants; D001323:Autoantibodies; D001324:Autoantigens; D051182:Desmogleins; D006680:HLA Antigens
keywords: Antioxidant; free radicals; oxidative stress; pemphigus vulgaris; reactive oxygen species