title: Graft-versus-host-like disease complicating thymoma: lack of AIRE expression as a cause of non-hereditary autoimmunity?
abstract: Three patients with graft-versus-host-like enterocolonopathy are reported. Their history was remarkable for thymoma and other autoimmune manifestations such as thrombocytopenia, red cell aplasia, interface dermatitis, Sjogren sialadenits, vanishing bile ducts and rheumatoid arthritis. In all patients, microsatellite analysis showed the autologous nature of the lymphocytes in the affected organs ruling out GVHD. In search for mechanisms that could mediate loss of tolerance to self-antigens we found in a panel of thymomas, including those of the three patients, a complete lack of autoimmune regulator (AIRE) and minimal expression of the transcription factor FOXP3 in the intra-tumoral T cells. AIRE is a recently discovered transcription factor which plays a key role in the maintenance of central tolerance and is mutated in the autosomal recessive autoimmune polyendocrinopathy syndrome APS-1. Our observations indicate that thymoma-related autoimmunity can potentially be elicited by an incomplete deletion of 'self'-specific T cells in concert with an insufficient formation of natural Tregs.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, The Netherlands.
authors.forename: G Johan
authors.initials: GJ
authors.lastname: Offerhaus
authors.forename: Marguerite E I
authors.initials: ME
authors.lastname: Schipper
authors.forename: Audrey J
authors.initials: AJ
authors.lastname: Lazenby
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Montgomery
authors.forename: Folkert H M
authors.initials: FH
authors.lastname: Morsink
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bende
authors.forename: Alex R
authors.initials: AR
authors.lastname: Musler
authors.forename: Rene A W
authors.initials: RA
authors.lastname: van Lier
authors.forename: Carel J M
authors.initials: CJ
authors.lastname: van Noesel
mesh_terms: D000328:Adult; D015551:Autoimmunity; D003092:Colitis / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D013945:Thymoma / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism; D013953:Thymus Neoplasms / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000096927:AIRE Protein
chemical_list: D051858:Forkhead Transcription Factors; D014157:Transcription Factors; D000096927:AIRE Protein; C418974:FOXP3 protein, human