Anti-tyrosinase-related protein-2 immune response in vitiligo patients and melanoma patients receiving active-specific immunotherapy.
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.
Okamoto
T
T
Department of Molecular Oncology, John Wayne Cancer Institute, Saint John's Health Center, Santa Monica, California 90404, USA.
Irie
R F
RF
Fujii
S
S
Huang
S K
SK
Nizze
A J
AJ
Morton
D L
DL
Hoon
D S
DS
D000906:Antibodies / Q000097:blood; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000276:immunology; D015153:Blotting, Western; D006801:Humans; D016233:Immunotherapy, Active; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000276:immunology*; D008545:Melanoma / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D010859:Pigmentation Disorders / Q000150:complications / Q000628:therapy; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014820:Vitiligo / Q000097:blood / Q000276:immunology* / Q000628:therapy*
D000906:Antibodies; D000951:Antigens, Neoplasm; D012333:RNA, Messenger; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase