title: Mitochondrial DNA acquires immunogenicity on exposure to nitrosative stress in patients with vitiligo.
abstract: Vitiligo is a common pigmentary skin disorder of unknown etiology. Many studies show the defective mitochondrial functionality in vitiligo patients, but the potential role of mitochondrial DNA (mtDNA) in the pathogenesis of vitiligo remains to be investigated. Recent evidences demonstrate that mitochondria possess their own nitric-oxide-synthase and can produce endogenous peroxynitrite (ONOO(-)). This study was undertaken to investigate the role of ONOO(-)-modified-mitochondrial-DNA (ONOO(-)-mtDNA) in vitiligo autoimmunity. Our data revealed that ONOO(-)-induced modifications in mtDNA caused structural alterations. Specificity of immunoglobulin G (IgG) from vitiligo patients (n=26) and controls (n=25) were analysed towards ONOO(-)-mtDNA. Vitligo-IgG samples (Vt-IgG) show preferential binding to ONOO(-)-mtDNA in comparison with native mtDNA (p<0.01). Anti-ONOO(-)-mtDNA-IgG show cross-reactivity with isolated DNA from vitiligo patients. Furthermore, levels of anti-ONOO(-)-mtDNA-IgG, inducible-nitric-oxide-synthase (iNOS), nitric oxide (NO) and nitrotyrosine were higher among vitiligo patients whose disease durations (DD) were ⩾5 years as compared to patients with lower DD (DD<5 years). In conclusion, this is the first study to demonstrate the role of ONOO(-)-modified mtDNA in vitiligo patients. Our data provide an important insight into the immunological mechanisms occur in vitiligo. The ONOO(-)-mtDNA may be useful in elucidating the mechanisms of disease pathogenesis.
authors.affiliation: Department of Dermatology, College of Medicine, Qassim University, Buraidah, Saudi Arabia.
authors.forename: Hani A
authors.initials: HA
authors.lastname: Al-Shobaili
authors.affiliation: Department of Medical Biochemistry, College of Medicine, Qassim University, Buraidah, Saudi Arabia. Electronic address: zafarrasheed@qumed.edu.sa.
authors.forename: Zafar
authors.initials: Z
authors.lastname: Rasheed
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D015538:Nitrosation; D030421:Peroxynitrous Acid / Q000276:immunology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014820:Vitiligo / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D004272:DNA, Mitochondrial; D007074:Immunoglobulin G; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase
keywords: Mitochondrial DNA; Nitrosative stress; ONOO(−)-mtDNA; Vitiligo; Vitiligo IgG