Autoantibodies to tyrosinase: the bridge between melanoma and vitiligo.
BACKGROUND
Tyrosinase is an enzyme that participates in the process of melanin production in normal melanocytes and melanoma cells. Enzymes are known to be autoantigens in various autoimmune disorders; thus, after the detection of antityrosinase antibodies in patients with vitiligo and melanoma, tyrosinase was defined as an autoantigen in these conditions. In some patients with melanoma the disease is associated with the appearance of "vitiligo-like" white patches on the skin, called melanoma-associated hypopigmentation (MAH). In this article, the authors summarize the recent data related to antityrosinase antibodies and expand on their role in the pathogenesis of vitiligo, melanoma, and MAH. In addition, the beneficial clinical applications of antityrosinase antibodies are presented.


METHODS
An enzyme-linked immunoadsorbent assay to detect the antityrosinase antibodies in the serum of patients and healthy volunteers was established using mushroom tyrosinase. Employing this method, antityrosinase antibodies were analyzed in a diverse group of patients with melanoma and vitiligo and in mice immunized with tyrosinase.


RESULTS
In patients with melanoma, those with metastatic disease had a higher titer of antityrosinase antibodies compared with healthy subjects, whereas patients with MAH and those with no evidence of disease had similar titers to the control group. The titer of antityrosinase antibodies in patients with metastatic melanoma treated by vaccination with antiidiotypic antibodies mimicking the high molecular weight melanoma-associated antigen (HMW MAA) initially increased after the vaccination and then decreased. High titers of antityrosinase antibodies were detected in patients with diffuse vitiligo compared with patients with localized disease and with the healthy control group. Mice immunized with tyrosinase generated a high titer of antityrosinase antibodies and after the inoculation of melanoma cells developed a lower number of lung metastases compared with an unvaccinated control group.


CONCLUSIONS
The appearance of antityrosinase autoantibodies in the serum of patients with metastatic melanoma and diffuse vitiligo is characterized by these two pathologies. The changes in the serum level of these autoantibodies in patients with melanoma after immunization with another antigen (HMW MAA) may have diagnostic and therapeutic implications.
Fishman
P
P
Laboratory of Clinical Immunology, Tel-Aviv University, Rabin Medical Center, Petach-Tikva, Israel.
Merimski
O
O
Baharav
E
E
Shoenfeld
Y
Y
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007167:Immunotherapy; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D051379:Mice; D014442:Monophenol Monooxygenase / Q000276:immunology*; D012878:Skin Neoplasms / Q000276:immunology* / Q000628:therapy; D014820:Vitiligo / Q000276:immunology*
D000951:Antigens, Neoplasm; D001323:Autoantibodies; D001324:Autoantigens; D014408:Biomarkers, Tumor; D014442:Monophenol Monooxygenase