ABSTRACT
Background: Pathogen infections have been associated with autoimmunity, which in turn has been implicated in the pathogenesis of vitiligo. However, the association between pathogen infections and vitiligo remains elusive. Aims: This study aimed to assess the proportion of individuals who tested positive for specific IgG antibodies against selected pathogens in patients with vitiligo and control subjects. Materials and Methods: Plasma from 51 patients with vitiligo and 51 age- and gender-matched controls were tested for anti-Toxoplasma gondii (T. gondii) IgG, anti-herpes simplex types 1 and 2 (HSV-1/2) IgG, anti-cytomegalovirus (CMV) IgG and anti-hepatitis C virus IgG. Results: Among all participants (n = 102), 63%, 84% and 87% tested positive for anti-T. gondii, anti-HSV-1/2 and anti-CMV IgG antibodies, respectively. Anti-hepatitis C virus IgG was negative in all samples tested. Positive anti-T. gondii IgG was detected in plasma samples of 39 (78%) patients with vitiligo and 25 (49%) controls (odds ratio [OR] 3.68, 95% confidence interval [CI] 1.55-8.76, P = 0.0036). Anti-HSV-1/2 IgG was detected in samples of 47 (92%) patients with vitiligo and 38 (76%) controls (OR 3.71, 95% CI 1.11-12.44, P = 0.031). Differences in frequencies of positive results for anti-T. gondii IgG and anti-HSV-1/2 IgG were only significant in samples from female patients with vitiligo when compared with controls (P = 0.036 and 0.024, respectively). Anti-CMV IgG was detected in samples from 46 patients with vitiligo (90%) and 41 (84%) controls (P = 0.384). Conclusions: T. gondii IgG and HSV-1/2 IgG were significantly more frequent in patients with vitiligo, especially in women, when compared with age- and gender-matched controls. Since T. gondii and HSV-1/2 infections can trigger autoimmune events, past exposure to these pathogens may be a risk factor for the development of vitiligo.
ABSTRACT
The melanocortin 1 receptor, a G protein-coupled receptor positively coupled to adenylyl cyclase, is a key regulator of epidermal melanocyte proliferation and differentiation and a determinant of human skin phototype and skin cancer risk. Despite its potential importance for regulation of pigmentation, no information is available on homologous desensitization of this receptor. We found that the human melanocortin 1 receptor (MC1R) and its mouse ortholog (Mc1r) undergo homologous desensitization in melanoma cells. Desensitization is not dependent on protein kinase A, protein kinase C, calcium mobilization, or MAPKs, but is agonist dose-dependent. Both melanoma cells and normal melanocytes express two members of the G protein-coupled receptor kinase (GRK) family, GRK2 and GRK6. Cotransfection of the receptor and GRK2 or GRK6 genes in heterologous cells demonstrated that GRK2 and GRK6 impair agonist-dependent signaling by MC1R or Mc1r. However, GRK6, but not GRK2, was able to inhibit MC1R agonist-independent constitutive signaling. Expression of a dominant negative GRK2 mutant in melanoma cells increased their cAMP response to agonists. Agonist-stimulated cAMP production decreased in melanoma cells enriched with GRK6 after stable transfection. Therefore, GRK2 and GRK6 seem to be key regulators of melanocortin 1 receptor signaling and may be important determinants of skin pigmentation.
