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

作者：Al Shobaili Hani A; Rasheed Zafar^*

来源：Human Immunology, 2014, 75(10): 1053-1061.

DOI：10.1016/j.humimm.2014.09.003

• Vitiligo
• Mitochondrial DNA
• Nitrosative stress
• ONOO--mtDNA
• Vitiligo IgG

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 mitochondria] 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.