Mitochondrial DNA acquires immunogenicity on exposure to nitrosative stress in patients with vitiligo

• Published in: Human immunology 2014-10, Vol.75 (10), p.1053-1061
• Main Authors: Al-Shobaili, Hani A, Rasheed, Zafar
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Allergy and Immunology; Autoantibodies - blood; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Autoimmunity - genetics; Autoimmunity - immunology; Child; DNA, Mitochondrial - genetics; DNA, Mitochondrial - immunology; Female; Humans; Immunoglobulin G - blood; Male; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial DNA; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; Nitrosation; Nitrosative stress; ONOO−-mtDNA; Peroxynitrous Acid - immunology; Tyrosine - analogs & derivatives; Tyrosine - metabolism; Vitiligo; Vitiligo - genetics; Vitiligo - immunology; Vitiligo IgG; Young Adult
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2014.09.003

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.