Antibodies to normal human melanocytes in vitiligo.

Naughton, Gail K.; Eisinger, Magdalena; Bystryn, Jean Claude

doi:10.1084/jem.158.1.246

Cited by 206 publications

(112 citation statements)

References 8 publications

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“…These examples include cases of spontaneous regression of primary and metastatic melanoma, and also the development of vitiligo in melanoma patients. These phenomena have been accompanied by various circulating anti-melanocyte antibodies and melanoma specific cytotoxicity conveyed by tumour infiltrating lymphocytes (Naughton et al, 1983;Bottger et al, 1992;Kawakami et al, 1994). Immunotherapy is most likely to eradicate metastatic disease when the tumour burden is minimal and when the host has not yet become immunosuppressed either by tumour itself (Akiyama et al, 1983), or by various chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

Autologous cell vaccine as a post operative adjuvant treatment for high-risk melanoma patients (AJCC stages III and IV)

Lotem¹,

Peretz²,

Drize³

et al. 2002

Br J Cancer

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This study evaluates the overall survival and disease free survival of melanoma patients that were treated with an autologous melanoma cell vaccine, administered as a post-operative adjuvant. Included are 43 patients with totally resected metastatic melanoma (28-AJCC stage III, 15-AJCC stage IV), with a median follow up of 34 months (6 -62). The treatment consisted of eight doses of a vaccine made of 10 -25610 6 autologous melanoma cells either released from the surgical specimen or grown in cell cultures. Tumour cells were conjugated with hapten dinitrophenyl, mixed with Bacille Calmette Guérin and irradiated to 110 Gy. Both disease free survival and overall survival were found to be correlated with intensity of evolving delayed type hypersensitivity to subcutaneous injection of unmodified melanoma cells. Patients with a delayed type hypersensitivity reaction of 510 mm had a median disease free survival of 17 months (mean 35 months) and a mean overall survival of 63 months (median not reached). In contrast, patients with a negative or weak delayed type hypersensitivity had a median disease free survival of 9 months (relative risk of recurrence=4.5, P=0.001), and a median overall survival of 16 months (relative risk of death=15, P=0.001). Stage III patients with a positive delayed type hypersensitivity reaction had an improved disease free survival of 16 months and a mean overall survival of 38 months, whereas patients with a negative delayed type hypersensitivity had a median disease free survival of 7 months (relative risk=4.5, P=0.02) and a median overall survival of 16 months (relative risk=9.5, P=0.005). The adjuvant administration of autologous melanoma vaccine was associated with improved disease-free and overall survival to selected patients who successfully attained anti-melanoma reactivity as detected by positive delayed type hypersensitivity reactions to unmodified melanoma cells.

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Section: Discussionmentioning

confidence: 99%

Autologous cell vaccine as a post operative adjuvant treatment for high-risk melanoma patients (AJCC stages III and IV)

Lotem¹,

Peretz²,

Drize³

et al. 2002

Br J Cancer

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“…2 antibodies directed at melanoma, as well as cultured melanocytes (32)(33)(34). It is unclear what the incidence of antibodies to melanocytes or melanoma is among melanoma patients.…”

Section: Discussionmentioning

confidence: 99%

Serial studies of autologous antibody reactivity to melanoma. Relationship to clinical course and circulating immune complexes.

Vlock¹,

Kirkwood²

1985

J. Clin. Invest.

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The low titer and incidence of autologous antibody to melanoma has hampered its evaluation. Through acid dissociation and ultrafiltration of serum, we have been able to augment the autologous immune response in 9 of 10 patients studied. This result suggests that autologous antibody is present in most patients with melanoma, but is obscured by circulating antigen and the formation of immune complexes. Because native antibody and antibody derived from circulating immune complexes are produced by the host against physiologically relevant antigens, correlations can be made to clinical course. Serological studies of three patients with melanoma were performed with serum samples obtained over many months; these studies demonstrated correlations with tumor progression and clinical course.

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“…It has been suggested that vitiligo is, at least in part, caused by autoimmune responses mediated by cytotoxic T cells against melanocytes, causing depigmentation. In addition, many patients with vitiligo produce autoantibodies against proteins expressed in melanocytes (2)(3)(4). The lysis of human melanocytes by vitiligo patients' sera provides direct support for the autoimmune hypothesis of human vitiligo (5).…”

mentioning

confidence: 93%

“…Peptides (5 g) were spotted on the activated membranes and left to dry at room temperature. To block nonspecific binding sites, membranes were incubated for 1 h in PBS/0.05% (v/v) Tween 20 (PBST) containing 5% BSA and then with human polyclonal Ab (pAbs) 3 (250 g/10 ml incubation solution). Following 1 h incubation at room temperature (RT), membranes were washed for 10 min with PBST (3ϫ) and further incubated in PBST/5% BSA for 1 h with HRP-conjugated goat anti-human polyclonal Abs (1/10000) obtained from Sigma-Aldrich.…”

Section: Dot-blot Immunoassaymentioning

confidence: 99%

Proteomic Scan for Tyrosinase Peptide Antigenic Pattern in Vitiligo and Melanoma: Role of Sequence Similarity and HLA-DR1 Affinity

Lucchese

Willers

Mittelman

et al. 2005

The Journal of Immunology

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Immune responses contribute to the pathogenesis of vitiligo and target melanoma sometimes associated with vitiligo-like depigmentation in some melanoma patients. We analyzed the sera from patients with vitiligo and cutaneous melanoma for reactivity toward tyrosinase peptide sequences 1) endowed with low level of similarity to human proteome, and 2) potentially able to bind HLA-DR1 Ags. We report that the tyrosinase autoantigen was immunorecognized with the same molecular pattern by sera from vitiligo and melanoma patients. Five autoantigen peptides composed the immunodominant anti-tyrosinase response: aa95–104FMGFNCGNCK; aa175–182 LFVWMHYY; aa176–190FVWMHYYVSMDALLG; aa222–236IQKLTGDENFTIPYW, and aa233–247 IPYWDWRDAEKCDIC. All of the five antigenic peptides were characterized by being (or containing) a sequence with low similarity level to the self proteome. Sera from healthy subjects were responsive to aa95–104FMGFNCGNCK, aa222–236IQKLTGDENFTIPYW, and aa233–247 IPYWDWRDAEKCDIC, but did not react with the aa175–182LFVWMHYY and aa176–190FVWMHYYVSMDALLG peptide sequences containing the copper-binding His180 and the oculocutaneous albinism I-A variant position F176. Our results indicate a clear-cut link between peptide immunogenicity and low similarity level of the corresponding amino acid sequence, and are an example of a comparative analysis that might allow to comprehensively distinguish the epitopic peptide sequences within a disease from those associated to natural autoantibodies. In particular, these data, for the first time, delineate the linear B epitope pattern on tyrosinase autoantigen and provide definitive evidence of humoral immune responses against tyrosinase.

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Antibodies to normal human melanocytes in vitiligo.

Cited by 206 publications

References 8 publications

Autologous cell vaccine as a post operative adjuvant treatment for high-risk melanoma patients (AJCC stages III and IV)

Autologous cell vaccine as a post operative adjuvant treatment for high-risk melanoma patients (AJCC stages III and IV)

Serial studies of autologous antibody reactivity to melanoma. Relationship to clinical course and circulating immune complexes.

Proteomic Scan for Tyrosinase Peptide Antigenic Pattern in Vitiligo and Melanoma: Role of Sequence Similarity and HLA-DR1 Affinity

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