Original Article
Journal of Investigative Dermatology (1998) 111, 1034–1039; doi:10.1046/j.1523-1747.1998.00411.x
Anti-Tyrosinase-Related Protein-2 Immune Response in Vitiligo Patients and Melanoma Patients Receiving Active-Specific Immunotherapy
Tetsuro Okamoto, Reiko F Irie*, Shigeyuki Fujii, Sharon K S Huang, Anne J Nizze†, Donald L Morton† and Dave S B Hoon
- Department of Molecular Oncology Santa Monica, California, U.S.A
- *Department of Biotechnology Santa Monica, California, U.S.A
- †John Wayne Cancer Clinic, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, California, U.S.A
Correspondence: Dr Dave S. B. Hoon, Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA 90404
Received 22 April 1998; Revised 18 June 1998; Accepted 29 July 1998.
Abstract
Several melanosome glycoproteins have been shown to be antigenic in humans. Correlation of antigen-specific immune responses in patients with the autoimmune disease vitiligo, therapy-induced hypopigmentation, and cutaneous melanoma has not been well studied. We examined antibody responses to a melanocyte autoantigen, tyrosinase-related protein-2 (TRP-2), as it is highly expressed in cutaneous melanoma and melanocytes. TRP-2 recombinant protein was synthesized for western blot and affinity anti-TRP-2 enzyme-linked immunosorbent assay. We demonstrated that patients with malignant melanoma, vitiligo, and active-specific immunotherapy-induced depigmentation had significant anti-TRP-2 IgG titers. The highest level of anti-TRP-2 IgG response was found in vitiligo patients. Induction and enhancement of anti-TRP-2 IgG responses were observed in melanoma patients treated with a polyvalent melanoma cell vaccine containing TRP-2. Active-specific immunotherapy could induce and/or augment the TRP-2 IgG antibody titers. Melanoma patients who developed hypopigmentation and had improved survival after polyvalent melanoma cell vaccine had significantly augmented anti-TRP-2 antibody responses compared with patients with poor prognosis. This study demonstrates that TRP-2 autoantigen is immunogenic in humans. TRP-2 antibody responses provide a linkage between autoimmune responses by vitiligo patients and melanoma patients responding to immunotherapy who have induced hypopigmentation.
Keywords:
autoantibodies, autoimmunity, human-clinical studies, tumor immunity
Abbreviations:
MAA, melanoma-associated antigen; MAH, melanoma-associated hypopigmentation; PMCV, polyvalent melanoma cell vaccine; TRP-1,2, tyrosinase-related protein 1 and 2



