Titin and ryanodine receptor epitopes are expressed in cortical thymoma along with costimulatory molecules.
Cortical-type thymomas are associated with myasthenia gravis (MG) in 50% of the cases. MG is caused by antibodies against the acetylcholine receptors (AChR), but additional non-AChR muscle autoantibodies such as those against titin and ryanodine receptor (RyR) are found in up to 95% of MG patients with thymoma. To elucidate the induction of non-AChR autoantibodies in thymoma-associated MG, we studied cortical-type thymomas from seven thymoma MG patients, and sera from six of them. All six had titin antibodies, and four had RyR antibodies. Titin and RyR epitopes were co-expressed along with LFA3 and B7 (BB1) costimulatory molecules on thymoma antigen-presenting cells (APC) in all thymomas. In normal thymus, the staining by anti-titin, anti-RyR, anti-LFA3, and anti-BB1 antibodies was weak and occurred exclusively in the medulla and perivascularly. Our results indicate a primary autosensitization against titin and RyR antigens inside the thymoma. In MG-associated thymoma, the mechanisms involved in the initial autosensitization against titin and RyR are probably similar to those implicated in the autosensitization against AChR. In all cases, there is an overexpression of muscle-like epitopes and costimulatory molecules indicating that the T-cell autoimmunization is actively promoted by the pathogenic microenvironment inside the thymoma.
Romi
Fredrik
F
Department of Neurology, Haukeland University Hospital, 5021, Bergen, Norway. fredrik.romi@haukeland.no
Bø
Lars
L
Skeie
Geir Olve
GO
Myking
Andreas
A
Aarli
Johan A
JA
Gilhus
Nils Erik
NE
D000328:Adult; D000368:Aged; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D018122:B7-1 Antigen / Q000097:blood / Q000276:immunology*; D018968:CD58 Antigens / Q000097:blood / Q000276:immunology*; D002675:Child, Preschool; D064211:Connectin; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000097:blood / Q000276:immunology*; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000097:blood / Q000276:immunology*; D009157:Myasthenia Gravis / Q000097:blood / Q000150:complications / Q000276:immunology*; D011494:Protein Kinases / Q000097:blood / Q000276:immunology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000097:blood / Q000276:immunology*; D013945:Thymoma / Q000097:blood / Q000276:immunology* / Q000473:pathology; D013953:Thymus Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology
D001323:Autoantibodies; D018122:B7-1 Antigen; D018968:CD58 Antigens; D064211:Connectin; D000939:Epitopes; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; C577285:TTN protein, human; D011494:Protein Kinases