Reactivity to tyrosinase: expression in cancer (melanoma) and autoimmunity (vitiligo).

Anti-tyrosinase antibodies are found in the sera of patients with diffuse vitiligo, metastatic melanoma and in sera of patients with melanoma and hypopigmentation (MAH). The autoantigen is tyrosinase itself, the enzyme that participates in pigment (melanin) formation by both melanocytes and melanoma cells. The production of autoantibodies in both diseases is associated with the development of white patches on the patients' skin. The presence of these autoantibodies in patients with melanoma may suggest a better prognosis. Cross-antigenicity between melanoma cells and normal melanocytes is most probably the key mechanism leading to the appearance of MAH. Anti-tyrosinase antibodies are absorbed by melanocytes and by melanoma cells in all the 3 situations (melanoma, vitiligo, MAH). However, since the production of antibodies in vitiligo exceeds that in melanoma or MAH, the antibodies are detected in significantly higher levels only in vitiligo. It is suggested here that anti-tyrosinase antibodies may be responsible, or at least participate in destruction of normal melanocytes during the immune response to melanoma antigens. This mechanism may be responsible for the phenomenon of MAH in patients with melanoma, and for the formation of the autoimmune vitiligo. Anti-tyrosinase antibodies may serve for two clinical applications. One is a marker for monitoring and follow up of patients with melanoma treated by immune therapy. The second is active (or passive) immunotherapy. We have recently shown that C57BL/6J mice immunized with tyrosinase generated a high titer of antityrosinase antibodies, and following the inoculation of melanoma cells developed lower number of lung metastases, compared to the unvaccinated control group.

[1]  P. Fishman,et al.  Tyrosinase as an autoantigen in patients with vitiligo , 1996, Clinical and experimental immunology.

[2]  P. Fishman,et al.  Anti-tyrosinase antibodies in malignant melanoma , 1996, Cancer Immunology, Immunotherapy.

[3]  P. Fishman,et al.  Anti-tyrosinase antibodies participate in the immune response to vaccination with anti-idiotypic antibodies mimicking the high-molecular-weight melanoma-associated antigen , 1995, Melanoma research.

[4]  A. Wiik,et al.  Characterization of biologically active antineutrophil cytoplasmic antibodies induced in mice. Pathogenetic role in experimental vasculitis. , 1995, Arthritis and rheumatism.

[5]  N. Maclaren,et al.  The role of tyrosinase in autoimmune vitiligo , 1994, The Lancet.

[6]  P. Fishman,et al.  Antigens and antibodies in malignant melanoma. , 1994, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine.

[7]  P. Fishman,et al.  Vitiligo autoantibodies are effective against melanoma , 1993, Cancer.

[8]  R. B. Goudie,et al.  Abnormal expression of MHC class II and ICAM‐1 by melanocytes in vitiligo , 1993, The Journal of pathology.

[9]  Y. Shoenfeld,et al.  Induction of experimental anti-phospholipid syndrome associated with SLE following immunization with human monoclonal pathogenic anti-DNA idiotype. , 1992, Journal of autoimmunity.

[10]  J. Bystryn,et al.  Identification of pigment cell antigens defined by vitiligo antibodies. , 1992, The Journal of investigative dermatology.

[11]  N. Farid,et al.  HLA-DR1 is associated with vitiligo. , 1991, Immunology letters.

[12]  G. Dunston,et al.  Vitiligo is associated with HLA-DR4 in black patients. A preliminary report. , 1990, Archives of dermatology.

[13]  E. Rosengren,et al.  Enzyme release from cultured human melanoma cells. , 1990, Acta Dermato-Venereologica.

[14]  E. Rosengren,et al.  Isolation of soluble tyrosinase from human melanoma cells. , 1990, Acta dermato-venereologica.

[15]  B. Sonesson,et al.  Tyrosinase activity in the serum of patients with malignant melanoma , 1995, Acta dermato-venereologica.

[16]  H. Yamamoto,et al.  Melanin production in cultured albino melanocytes transfected with mouse tyrosinase cDNA. , 1989, Idengaku zasshi.

[17]  J. Bystryn,et al.  Serum antibodies in vitiligo patients. , 1989, Clinics in dermatology.

[18]  V. Hearing,et al.  Specific identification of an authentic clone for mammalian tyrosinase. , 1989, The Journal of biological chemistry.

[19]  D. Emerson,et al.  Western blot analysis of serum antibody reactivity with human melanoma cell antigens in alopecia areata and vitiligo. , 1988, Clinical immunology and immunopathology.

[20]  J. Bystryn,et al.  Evidence for immunologic mechanisms in human vitiligo: patients' sera induce damage to human melanocytes in vitro by complement-mediated damage and antibody-dependent cellular cytotoxicity. , 1988, The Journal of investigative dermatology.

[21]  G. Naughton,et al.  Correlation between vitiligo antibodies and extent of depigmentation in vitiligo. , 1986, Journal of the American Academy of Dermatology.

[22]  S. Shibahara,et al.  Cloning and expression of cDNA encoding mouse tyrosinase. , 1986, Nucleic acids research.

[23]  R. Gupta,et al.  Studies of a melanoma tumor-associated antigen detected in the spent culture medium of a human melanoma cell line by allogeneic antibody. III. Physicochemical properties. , 1984, Journal of the National Cancer Institute.

[24]  M. Mihm,et al.  Malignant melanoma and vitiligo-like leukoderma: an electron microscopic study. , 1983, Journal of the American Academy of Dermatology.

[25]  G. Naughton,et al.  Antibodies to normal human melanocytes in vitiligo , 1983, The Journal of experimental medicine.

[26]  P. Grimes,et al.  Autoantibodies and their clinical significance in a black vitiligo population. , 1983, Archives of dermatology.

[27]  N. Lowe,et al.  Association of HLA-DR4 with vitiligo. , 1983, Journal of the American Academy of Dermatology.

[28]  M. el-Mofty,et al.  Vitiligo. A symptom complex. , 1980, International journal of dermatology.

[29]  E. McBurney.  Vitiligo. Clinical picture and pathogenesis. , 1979, Archives of internal medicine.

[30]  S. Katz,et al.  Autoimmune vitiligo: detection of antibodies to melanin-producing cells. , 1977, The New England journal of medicine.

[31]  J. Nordlund,et al.  Should vitiligo be induced in patients after resection of primary melanoma. , 1977, Archives of dermatology.

[32]  A. Peserico,et al.  Autoantibodies in vitiligo. , 1976, Archives of dermatology.

[33]  Ackerman Lv,et al.  Uveitis and vitiligo associated with BCG treatment for malignant melanoma. , 1974 .

[34]  Hornung Mo,et al.  Specific tissue and tumor responses of chimpanzees following immunization against human melanoma. , 1974 .

[35]  L. Deppisch,et al.  Generalized melanosis secondary to malignant melanoma. Report of a case with serum and tissue tyrosinase studies , 1969, Cancer.

[36]  J. Brostoff.  Autoantibodies in patients with vitiligo. , 1969, Lancet.