Identification of CTLA-4 isoforms produced by alternative splicing and their association with myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness induced by autoantibodies against the acetylcholine receptor. CTLA-4 (CD152) plays an inhibitory role in the immune response and has been suggested to be involved in the pathophysiology of MG. In this study, we focused...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 128(2008), 3 vom: 15. Sept., Seite 374-81
1. Verfasser: Gu, Ming (VerfasserIn)
Weitere Verfasser: Kakoulidou, Maria, Giscombe, Ricardo, Pirskanen, Ritva, Lefvert, Ann Kari, Klareskog, Lars, Wang, XiongBiao
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2008
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Antigens, CD CTLA-4 Antigen CTLA4 protein, human Protein Isoforms RNA, Messenger
Beschreibung
Zusammenfassung:Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness induced by autoantibodies against the acetylcholine receptor. CTLA-4 (CD152) plays an inhibitory role in the immune response and has been suggested to be involved in the pathophysiology of MG. In this study, we focused on alternative CTLA-4 mRNA expression in PBMCs from MG patients. We defined two new isoforms of CTLA-4 mRNA that arise due to alternative splicing. By semi-quantitative RT-PCR analysis, we observed a lower expression of sCTLA-4 mRNA relative to the membrane form in MG patients. In addition, the MG patients had lower levels of sCTLA-4 mRNA in PBMCs compared to healthy controls, as assessed by real-time PCR. One of the spliced isoforms (LCTLA-4) was more prevalent in MG patients compared to healthy controls. The alternative splicing was not associated with sex, thymectomy, serum levels of anti-AChR, immunosuppressive treatment or the four CTLA-4 gene polymorphisms analyzed. This study reveals an abnormal spectrum of mRNA expression of CTLA-4 in MG patients, which marks the importance of studying gene expression of alternative splicing
Beschreibung:Date Completed 05.09.2008
Date Revised 17.11.2011
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2008.05.006