Difference in Pathogenesis Between Vitiligo Vulgaris and Halo Nevi Associated with Vitiligo is Supported by an HLA Association Study

Abstract

Human leukocyte antigen (HLA) class II associations with two subtypes of vitiligo: vitiligo vulgaris and halo nevi associated with vitiligo were investigated. In previous studies associations between vitiligo and HLA antigens have been reported but these two subtypes have never been taken into account. However from a clinical and histological point of view, a difference in (auto)-immune pathogenesis can be expected. This difference might be reflected in an association with different HLA alleles. Seventy-six unrelated Dutch Caucasians, 40 with vitiligo vulgaris and 36 with halo nevi associated with vitiligo were included. A panel of randomly chosen HLA typed healthy Dutch blood donors (n = 2400) served as control population. HLA-DR and -DQ typing was carried out on blood samples by amplifying genomic DNA using polymerase chain reaction followed by dot blot hybridization with sequence specific oligonucleotides. The main outcome measures were odds ratio (OR), uncorrected P-value (P(u)) and corrected P-value. There were distinct differences in the clinical manifestations between vitiligo vulgaris and halo nevi associated with vitiligo with respect to precipitating factors, extent and progress of the disease and the association with other auto-immune diseases in the two subtypes and their respective first degree family members. Our stratification reveals differences in HLA class II between both subtypes and between subtypes and controls. A case-control association study showed a significant positive association of HLA-DR4 (OR = 2.787, P(u) = 0.0022) and DR53 (OR = 2.249, P(u) = 0.0153) and a negative association of HLA-DR3 (OR = 0.195, P(u) = 0.0024) with vitiligo vulgaris. The group with halo nevi associated with vitiligo did not show these associations, but had a significant negative association with HLA-DR11 (OR = 0.083, P(u) = 0.0067). In conclusion, the differences in HLA association within clinical subtypes of vitiligo support our suggestion that vitiligo vulgaris and halo nevi associated with vitiligo have distinct pathogenic mechanisms.

Physiopathology and genetics of vitiligo

“…More interestingly, a polygenetic additive model was found to be the best model for segmental, localized, acrofacial and generalized vitiligo, whereas the best model for universal vitiligo was an environmental one. In an additional study, Human leukocyte antigen (HLA) class II associations with two subtypes of vitiligo, vitiligo vulgaris and halo nevi associated with vitiligo, were investigated [34]. A case-control association study showed a significant positive association of HLA-DR4 and DR53 and a negative association of HLA-DR3 with vitiligo vulgaris.…”

Vitiligo, reactive oxygen species and T-cells

“…There can be shared pathomechanisms with ordinary vitiligo. Depigmentation around melanocytic nevi (halo nevi) can resemble vitiligo, and the two conditions can be associated [10]. A regressing melanoma can also demonstrate vitiligo-like depigmentation.…”

Polymorphisms in the Melanocortin-1 Receptor (Mc1R) Gene in Vitiligo

“…Although Vijlder et al (12) found a positive relation with HLADR4 and HLADR53, they could not show any relation between HLADR3 and vitiligo.…”