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Title: Identification and characterisation of novel antibody targets in vitiligo
Author: Faraj, Safa
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2018
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Vitiligo is an acquired, non-contagious depigmenting skin disease results from epidermal melanocyte loss. Accumulating evidence suggests a role for autoimmunity in vitiligo aetiology, as antibodies and autoreactive T cells against melanocyte autoantigens can be detected in vitiligo patients. As part of determining the pathomechanisms involved in the development of vitiligo, identifying the specific targets of the immune reactivity in patients is a major goal in the vitiligo research field. A better understanding of vitiligo aetiology may help to develop successful treatment and diagnostic modalities. One of the main aims of this study was to identify novel autoantigens in vitiligo using phage-display technology; a melanocyte cDNA phage-display library was immunoscreened with IgG from 22 vitiligo patients. Several autoantigens were enriched by this technique, including ones already known (tyrosinase, tyrosinase-related protein 1, melanocyte-specific protein PMEL, L-dopachrome tautomerase, heat-shock protein 90, ribosomal protein L24, and LaminA). Additionally, humoral immune reactivities were identified against previously unreported putative autoantigens glycoprotein nonmetastatic melanoma protein b (GPNMB), OCA2-encoded P protein (OCA2 protein), melanocortin-1 receptor, and GTP-binding protein Rab27A. The frequency of GPNMB, OCA2 protein, and LaminA antibodies in sera from healthy subjects (n = 100) and non-segmental (n = 231), segmental (n = 4) or focal (n = 11) vitiligo patients was investigated using radioligand binding assays (RLBAs). Healthy individuals were all negative for all antibodies tested. In the non-segmental vitiligo patient group, 91/231 (39%) were positive for GPNMB antibodies and this was statistically significant when compared with healthy controls (P = < 0.0001). The frequency of GPNMB antibody was significantly higher in the non-segmental vitiligo patient group with active disease compared to those with stable disease (P = 0.006). OCA2 protein and LaminA antibodies were detected at an overall frequency of 22%. GPNMB, OCA2 protein, and LaminA were antibody targets in both patient groups with and without accompanying autoimmune disease. Overall, the study identified GPNMB, OCA2 protein, and LaminA as autoantigens in vitiligo further supporting a role for autoimmunity in vitiligo development.
Supervisor: Kemp, Elizabeth Helen ; Weetman, Anthony ; Gawkrodger, David Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available