1/13. Vogt-Koyanagi-Harada syndrome after cutaneous injury.OBJECTIVE: To describe three patients who developed Vogt-Koyanagi-Harada syndrome (VKH) after cutaneous injury. DESIGN: Retrospective case series. PARTICIPANTS: Three patients seen in the uveitis clinic at Aravind eye Hospital and Postgraduate Institute of ophthalmology, Madurai, india, participated. MAIN OUTCOME MEASURES: The history, evaluation, and management of the three patients were summarized. RESULTS: Three patients developed VKH syndrome shortly after cutaneous injury. In each case, the affected area of skin became vitiliginous on healing and simultaneous with the onset of ocular symptoms. One patient developed additional ectopic areas of vitiligo. All three patients developed chronic, bilateral, diffuse uveitis, one associated with an exudative retinal detachment and two with Dalen-Fuchs-like nodules. Well-recognized complications of VKH syndrome that occurred in the authors' patients included geographic atrophy of the retinal pigment epithelium (3 of 3), cataract (3 of 3), and glaucoma (1 of 3). Ocular inflammation was well controlled in each patient with local or systemic corticosteroids or both. In one patient, the area of vitiligo showed increased pigmentation in response to systemic corticosteroid treatment. CONCLUSIONS: Vogt-Koyanagi-Harada syndrome may follow cutaneous injury, supporting the notion that this disorder may result from systemic sensitization to shared melanocytic antigens.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/13. Clonal expansion of Melan A-specific cytotoxic T lymphocytes in a melanoma patient responding to continued immunization with melanoma-associated peptides.peptides derived from human tumor antigens have been used in a number of clinical trials to induce specific immune responses against autologous tumors in cancer patients. Although favorable clinical results were observed in single patients, immune responses correlating with tumor regression were either not detected or in case of responses, the T-cell specificity was difficult to demonstrate. In this study, we analyzed antigen-specific T-cell responses induced in the skin and in peripheral blood lymphocytes (PBL) in an HLA-A2-positive melanoma patient. The patient showed major regression of metastatic melanoma under continued immunization with peptides derived from the melanocyte differentiation antigens Melan A/MART-1, tyrosinase and gp100/Pmel17. Based on the identification of different T-cell receptor (TCR) families reactive with Melan A/MART-1, we have demonstrated that i.d. immunization with peptides alone leads to oligoclonal expansion of Melan A/MART-1-specific cytotoxic T lymphocytes (CTL), detectable in local delayed-type hypersensitivity (DTH) reactions and PBL. A monoclonal expansion of a Melan A/MART-1-specific TCR VB 16 CTL was reproducibly observed after in vitro stimulation with Melan A/MART-1 peptides. The same TCR VB 16 CTL clone was detected in skin biopsies taken from vitiligo areas. Our findings provide strong evidence for the effective induction of specific T-cell responses to Melan A/MART-1 by i.d. immunization with peptide alone, which accounts for dermal depigmentation, specific cytotoxicity against Melan A/MART-1-expressing melanoma cells and clinical tumor regression.- - - - - - - - - - ranking = 3keywords = antigen (Clic here for more details about this article) |
3/13. Melanocyte destruction after antigen-specific immunotherapy of melanoma: direct evidence of t cell-mediated vitiligo.Current strategies for the immunotherapy of melanoma include augmentation of the immune response to tumor antigens represented by melanosomal proteins such as tyrosinase, gp100, and MART-1. The possibility that intentional targeting of tumor antigens representing normal proteins can result in autoimmune toxicity has been postulated but never demonstrated previously in humans. In this study, we describe a patient with metastatic melanoma who developed inflammatory lesions circumscribing pigmented areas of skin after an infusion of MART-1-specific CD8( ) T cell clones. Analysis of the infiltrating lymphocytes in skin and tumor biopsies using T cell-specific peptide-major histocompatibility complex tetramers demonstrated a localized predominance of MART-1-specific CD8( ) T cells (>28% of all CD8 T cells) that was identical to the infused clones (as confirmed by sequencing of the complementarity-determining region 3). In contrast to skin biopsies obtained from the patient before T cell infusion, postinfusion biopsies demonstrated loss of MART-1 expression, evidence of melanocyte damage, and the complete absence of melanocytes in affected regions of the skin. This study provides, for the first time, direct evidence in humans that antigen-specific immunotherapy can target not only antigen-positive tumor cells in vivo but also normal tissues expressing the shared tumor antigen.- - - - - - - - - - ranking = 9keywords = antigen (Clic here for more details about this article) |
4/13. Tumor antigens isolated from a patient with vitiligo and T-cell-infiltrated melanoma.Serological identification of tumor antigens by cDNA expression cloning is a technique used to isolate cDNAs encoding tumor antigens that are recognized by IgG antibodies in sera from cancer patients. It is also useful for the isolation of tumor antigens recognized by T cells. We applied this method to identify melanoma antigens recognized by the serum from a patient with a good prognosis who had T-cell-infiltrated melanoma and vitiligo. By screening a lambda phage cDNA library constructed from a highly pigmented melanoma cell line, SKmel23, with the patient's serum, 50 positive cDNA clones consisting of 26 distinct antigens were isolated. Of these, 20 encoded known proteins, and 6 encoded previously uncharacterized ones. The most frequently isolated clone, which we named KU-MEL-1, was unknown previously but was homologous to partial cDNA sequences registered in the expressed sequence tag database. reverse transcription-PCR and Northern blot analysis demonstrated that KU-MEL-1 was strongly expressed in most melanoma cell lines, melanoma tissue samples, and cultured melanocytes and weakly expressed in cell lines derived from other types of tumors, as well as in some normal tissues, including testis. Western blot analysis with polyclonal murine antibody generated by immunization with the recombinant KU-MEL-1 protein demonstrated that the KU-MEL-1 protein was preferentially expressed in melanoma cells and melanocytes. IgG antibodies against KU-MEL-1 were detected in the sera from 9 of 26 melanoma patients and from some patients with other cancers, including brain tumor, esophageal cancer, colon cancer, and chronic myelogenous leukemia, but were not detected in sera from 30 healthy individuals. Although the IgG specific for KU-MEL-1 was not detected in sera from 12 vitiligo patients, it was detected in sera from 7 of 11 patients with Vogt-Koyanagi-Harada disease that is thought to be an autoimmune disease against melanocytes. These results suggest that KU-MEL-1 may be a useful target for the development of diagnostic and therapeutic methods for patients with various cancers, particularly with melanoma, as well as patients with autoimmune diseases against melanocytes.- - - - - - - - - - ranking = 9keywords = antigen (Clic here for more details about this article) |
5/13. Differential expression of inhibitory or activating CD94/NKG2 subtypes on MART-1-reactive T cells in vitiligo versus melanoma: a case report.Selection and activation of T cells is tightly regulated by both antigen-specific receptors and co-receptors to ensure that responses to self antigens are largely avoided. By T cell receptor clonotypic mapping and staining with tetrameric HLA-peptide complexes, we demonstrate the presence of melanocyte differentiation antigen MART-1 specific T cells in the areas of destruction of both neoplastic and normal melanocytic cells in a case of a primary melanoma and its associated hypopigmentation. These self reactive T cells expressed CD94/NKG2 major histocompatibility complex class I specific C-type lectin-like receptors. This family of receptors includes both activating and inhibitory isoforms. Thus, we performed a detailed analysis that revealed the exclusive presence of inhibitory NKG2-A/B receptors in the vitiligo-like leukoderma, whereas both the inhibitory receptors and the activating NKG2-C/E isoforms were present within the tumor. Our data suggest the differential expression of killer inhibitory receptors as a possible mechanism to regulate T cell responses to self antigens.- - - - - - - - - - ranking = 4keywords = antigen (Clic here for more details about this article) |
6/13. Full-blown hypothyroidism associated with vitiligo and acropachy. Report of one case.During the first two years after the onset of hypothyroidism, a patient with spontaneous primary myxedema developed thyroid acropachy. Fifteen years before the diagnosis of thyroid disease, he had patchy vitiligo of the face. There were high serum levels of antibodies against thyroglobulin (anti-Tg) and microsomal antigen (anti-M) were present, while the serum levels of antibodies against the second antigen of the colloid and the cell-surface antigen fell within the normal range. Moreover, antibodies to gastric parietal cells, adrenocortical cells or pancreatic islets in the serum were not present. Concerning the immuno-genetic pattern of our patient, his HLA system did not appear to confirm the well documented prevalence in whites with autoimmune disorders of an antigen specificity positive for the locus DR3.- - - - - - - - - - ranking = 4keywords = antigen (Clic here for more details about this article) |
7/13. Vogt-Koyanagi-Harada syndrome following injury-induced progressive vitiligo.We report a case of Vogt-Koyanagi-Harada (VKH), Syndrome wherein the patient developed ocular symptoms following injury-induced progressive vitiligo with immunologic evidence from the skin biopsy specimen of the vitiligo. This case supports the hypothesis that the cell-mediated immune process against a common melanocyte antigen plays an important role in the development and progression of the disease.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
8/13. Pathogenetic mechanisms of vitiligo in a patient with sezary syndrome.patients exhibiting association between vitiligo and cutaneous T-cell lymphoma (CTCL) remain rare and it is not known whether some T-cell subpopulations of CTCL in the skin are able to recognize specific melanocytic epitopes and thus induce vitiligo. The aim of our study was to determine whether T cells specific to melanocyte differentiation antigens were detectable among tumour-infiltrating lymphocytes (TIL) in the hypopigmented skin of a patient with sezary syndrome (SS). A 71-year-old patient presented with SS and developed vitiligo during the course of her disease. Immunohistochemical studies showed staining with HMB45 and MelanA antibodies in the pigmented skin biopsy, whereas no staining was observed in the hypopigmented skin biopsy. To analyse responses to melanocyte differentiation antigens, we used a transient COS transfection assay that permits an estimation of CD8 T-cell responses against a large number of HLA/antigen combinations. This technique allowed the detection of melanocyte differentiation antigen-specific T lymphocytes, directed mainly against Melan-A/MART1 antigen in the HLA-A*23 context. Our study supports the concept that vitiligo that has developed during the evolution of a CTCL is related to the presence of a T-lymphocyte subpopulation reactive against melanocyte differentiation antigens (mainly Melan-A/MART1) present in skin lesions. The role of interferon in the induction of this T-lymphocyte subpopulation is discussed.- - - - - - - - - - ranking = 6keywords = antigen (Clic here for more details about this article) |
9/13. Chronic active hepatitis associated with vitiligo, nail dystrophy, alopecia and a new variant of LKM antibodies.In this report we describe the case of a 7-year-old boy, suffering from autoimmune-type chronic active hepatitis (AI-CAH) associated with vitiligo, nail dystrophy, alopecia areata and a variant of liver kidney microsomal (LKM) autoantibodies. This patient's antibodies are different from LKM-1 which are directed against cytochrome P450 db1. They react predominantly with perivenous hepatocytes in contrast to LKM-1 antibodies which homogeneously stain the whole liver lobule in immunofluorescence. In Western blot analysis this LKM variant reacts with a liver microsomal protein of approx. 50 kDa, but not with recombinant LKM-1 (cytochrome P450 db1) antigen. Immunosuppressive treatment led to a normalization of liver histology after 1 year and a significant improvement of vitiligo and alopecia areata. In summary, a case of autoimmune-type chronic active hepatitis is presented which is associated with a new variant of LKM antibodies reacting with a 50 kDa microsomal protein different from cytochrome P450 db1. Furthermore, this patient suffers from extrahepatic syndromes (alopecia, nail dystrophy) that have not been described previously in LKM antibody-positive chronic active hepatitis.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
10/13. A syndrome of immunoglobulin a deficiency, diabetes mellitus, malabsorption, a common HLA haplotype. Immunologic and genetic studies of forty-three family members.Three persons in a kindred of 43 had variable expression of a syndrome consisting of immunoglobulin a deficiency, diabetes mellitus, malabsorption, and a common HLA haplotype. Findings from the proband included life-threatening malabsorption; idiopathic intestinal mucosal atrophy with infalmmation; iga deficiency and antibodies to multiple endocrine organs; insulin-dependent diabetes mellitus; and the major histocomptability antigens HLA-A2, B8, and DW3. In addition to the described syndrome other conditions present in the family include Graves' disease, vitiligo, hypocomplementemia, rheumatic fever, multiple sclerosis, and a high frequency of antibodies to endocrine tissue. Since Graves' disease, diabetes mellitus, and idiopathic Addison's disease have all been described in association with HLS-B8 and DW3, we believe that the occurrence of these diseases in this family suggests that a single immune response gene or gene complex is linked with HLA-B8 and DW3.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
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