Autoantigens in vitiligo identified by the serological selection of a phage-displayed melanocyte cDNA expression library.
Vitiligo is an acquired idiopathic hypomelanotic disorder characterized by circumscribed depigmented macules resulting from the loss of cutaneous melanocytes. Although the exact cause of vitiligo remains obscure, autoimmunity may play a role in the development of the disease. The present study was undertaken to investigate the applicability of phage display technology to identify B-cell autoantigens in vitiligo. A melanocyte cDNA phage display library was subjected to rounds of enrichment with vitiligo patient IgG. Subsequently, enriched IgG-binding peptides representing putative autoantigens were identified by sequencing their encoding cDNAs. Radioimmunoassays were used to confirm the immunoreactivity of vitiligo patient (n=61) and control (n=28) sera to several of the putative autoantigens. Non-segmental vitiligo patient sera (n=53) were positive for antibody (Ab) reactivity to gamma-enolase (8%); alpha-enolase (9%); heat-shock protein 90 (13%); osteopontin (4%); ubiquitin-conjugating enzyme (15%); translation-initiation factor 2 (6%); and GTP-binding protein, Rab38 (15%). Ab reactivity to at least one of the previously unknown autoantigens was detected in 51% of patients with non-segmental vitiligo. In contrast, Ab reactivity in a group of patients with segmental vitiligo (n=8) was not demonstrated. Overall, the study indicated that the targets of autoantibodies in vitiligo patients can be revealed by employing the methodology of phage display.
Waterman
Elizabeth A
EA
Department of Human Metabolism, School of Medicine, University of Sheffield, Sheffield, UK.
Gawkrodger
David J
DJ
Watson
Philip F
PF
Weetman
Anthony P
AP
Kemp
E Helen
EH
D000293:Adolescent; D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000235:genetics* / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology; D005260:Female; D015723:Gene Library; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008544:Melanocytes / Q000276:immunology / Q000502:physiology*; D008875:Middle Aged; D019151:Peptide Library; D011863:Radioimmunoassay; D014820:Vitiligo / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
D001324:Autoantigens; D007074:Immunoglobulin G; D019151:Peptide Library