Tyrosinase as an autoantigen in patients with vitiligo

Abstract

SUMMARYVitiligo is considered an autoimmune disorder due to the generation and presence of autoantibodies directed against melanocyte antigens in the patients' sera. In the present study we point towards a newly defined autoantigen in vitiligo, the enzyme tyrosinase, which participates in the process of melanogenesis. Anti-tyrosinase antibodies were detected in the sera of seven patients with diffuse and 11 patients with localized vitiligo. Employing solid-phase ELISA to mushroom tyrosinase, we found that patients with diffuse vitiligo had significantly higher titres of IgG anti-tyrosinase autoantibodies than patients with localized disease or healthy subjects. These anti-tyrosinase autoantibodies have relatively high functional affinity to tyrosinase and can be recovered from vitiligo patients' sera by affinity purification. The anti-tyrosinase antibodies do not cross-react with other enzymes recognized as autoantigens in different autoimmune disorders and the autoantibodies do not block the enzymatic activity of tyrosinase, indicating that they are not reacting with the catalytic site of the enzyme. These data point to tyrosinase as an autoantigen in vitiligo and suggest that anti-tyrosinase titres can serve as a marker for disease activity.

A single-nucleotide polymorphism in the gene encoding lymphoid protein tyrosine phosphatase (PTPN22) confers susceptibility to generalised vitiligo

“…The frequent association of vitiligo with autoimmune disorders and the demonstration of autoantibodies to melanosomal proteins in the serum of patients with the disease support this theory. [2][3][4][5][6] In addition, autoreactive CTLs, which specifically recognise melanocyte differentiation antigens, have been detected in both the peripheral blood and perilesional skin of individuals with vitiligo. [7][8][9] Melanocyte-specific CTLs have also been identified in patients with melanoma where vitiligo has occurred during immunotherapy and the adoptive transfer of melanoma antigen-specific CTLs may be associated with the regression of melanoma metastases and the appearance of vitiligo.…”

“…1 Support for this theory arises from the frequent association of vitiligo with autoimmune disorders and the demonstration of autoantibodies to melanosomal proteins in the serum of patients with the disease. [2][3][4][5][6] More recently, autoreactive cytotoxic T lymphocytes (CTLs), which specifically recognise melanocyte differentiation antigens, have been detected in both the peripheral blood and perilesional skin of individuals with vitiligo. [7][8][9] Furthermore, several genes that have a role in regulating immunity have been associated with susceptibility to vitiligo including: polymorphic markers in the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene, the autoimmune susceptibility loci AIS1, AIS2, AIS3 and SLEV1 and certain human leukocyte antigen specificities of the major histocompatibility complex.…”

Vitiligo: A comprehensive overview

“…144,[150][151][152] Vitiligo patient sera are able to damage melanocytes in vitro both by complement activation and by antibody-dependent cellular cytotoxicity, 150,153 and associated antibodies may also be able to damage melanocytes in vivo. 154 Cellular immunity.…”

Vitiligo Antibodies Are Not Directed to Tyrosinase

“…This may be of importance, since it has previously been reported that antibodies that react to melanocytes can be present independently of vitiligo in patients with certain associated endocrine disorders. 25 Subsequently, Baharav et al 12 reported that antibodies to mushroom tyrosinase were present in a group of 18 patients with vitiligo but not in healthy individuals. However, the antibodies were present only in a subgroup of 7 patients with diffuse vitiligo, and the actual percentage of these patients who had antibodies was not provided.…”