AUTOANTIBODIES TO TYROSINASE - THE BRIDGE BETWEEN MELANOMA AND VITILIGO

BACKGROUND. Tyrosinase is an enzyme that participates in the process o f melanin production in normal melanocytes and melanoma cells. Enzymes are known to be autoantigens in various autoimmune disorders; thus, a fter the detection of antityrosinase antibodies in patients with vitil igo and melanoma, tyrosinase was defined as an autoantigen in these co nditions. In some patients with melanoma the disease is associated wit h the appearance of ''vitiligo-like'' white patches on the skin, calle d melanoma-associated hypopigmentation (MAH). In this article, the aut hors summarize the recent data related to antityrosinase antibodies an d expand on their role in the pathogenesis of vitiligo, melanoma, and MAH. In addition, the beneficial clinical applications of antityrosina se antibodies are presented. METHODS. An enzyme-linked immunoadsorbent assay to detect the antityrosinase antibodies in the serum of patient s and healthy volunteers was established using mushroom tyrosinase. Em ploying this method, antityrosinase antibodies were analyzed in a dive rse group of patients with melanoma and vitiligo and in mice immunized with tyrosinase. RESULTS. In patients with melanoma, those with metas tatic disease had a higher titer of antityrosinase antibodies compared with healthy subjects, whereas patients with MAH and those with no ev idence of disease had similar titers to the control group. The titer o f antityrosinase antibodies in patients with metastatic melanoma treat ed by vaccination with antiidiotypic antibodies mimicking the high mol ecular weight melanoma-associated antigen (HMW MAA) initially increase d after the vaccination and then decreased. High titers of antityrosin ase antibodies were detected in patients with diffuse vitiligo compare d with patients with localized disease and with the healthy control gr oup. Mice immunized with tyrosinase generated a high titer of antityro sinase antibodies and after the inoculation of melanoma cells develope d a lower number of lung metastases compared with an unvaccinated cont rol group. CONCLUSIONS. The appearance of antityrosinase autoantibodie s in the serum of patients with metastatic melanoma and diffuse vitili go is characterized by these two pathologies. The changes in the serum level of these autoantibodies in patients with melanoma after immuniz ation with another antigen (HMW MAA) may have diagnostic and therapeut ic implications. (C) 1997 American Cancer Society.