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

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Citation

Gu M, Kakoulidou M, Giscombe R, Pirskanen R, Lefvert AK, Klareskog L, Wang X

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

Clin Immunol. 2008 Sep;128(3):374-81. doi: 10.1016/j.clim.2008.05.006. Epub 2008 Jul 2.

PubMed ID
18595775 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Cytotoxic T-lymphocyte protein 4P16410Details