Lack of correlation between the levels of soluble cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and the CT-60 genotypes

• Type of Material: Article
• Authors: Sharad Purohit, Medical College of Georgia; Robert Podolsky, Medical College of Georgia; Christin Collins, Emory University; Weipeng Zheng, Medical College of Georgia; Desmond Schatz, University of Florida; Andrew B. Muir, Emory University; Diane Hopkins, Medical College of Georgia; Yi-Hua Huang, Medical College of Georgia; Jin-Xiong She, Medical College of Georgia
• Language: English
• Date: 2005-10-31
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2005 Purohit et al; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://dx.doi.org/10.1186/1740-2557-2-8
• Title of Journal or Parent Work: Journal of Autoimmune Diseases
• ISSN: 1740-2557
• Volume: 2
• Start Page: 8
• End Page: 8
• Grant/Funding Information: SP was supported by a JDRF postdoctoral fellowship (JDRF #3-2004-195).; This work was supported by grants from the National Institute of Child Health and Development (2RO1HD37800 and 1R21HD050196) to JXS.
• Research Categories: Health Sciences, General; Biology, Microbiology

Abstract

Background: Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays a critical role in downregulation of antigen-activated immune response and polymorphisms at the CTLA-4 gene have been shown to be associated with several autoimmune diseases including type-1 diabetes (T1D). The etiological mutation was mapped to the CT60-A/G single nucleotide polymorphism (SNP) that is believed to control the processing and production of soluble CTLA-4 (sCTLA-4). Methods: We therefore determined sCTLA-4 protein levels in the sera from 82 T1D patients and 19 autoantibody positive (AbP) subjects and 117 autoantibody negative (AbN) controls using ELISA. The CT-60 SNP was genotyped for these samples by using PCR and restriction enzyme digestion of a 268 bp DNA segment containing the SNP. Genotyping of CT-60 SNP was confirmed by dye terminating sequencing reaction. Results: Higher levels of sCTLA-4 were observed in T1D (2.24 ng/ml) and AbP (mean = 2.17 ng/ml) subjects compared to AbN controls (mean = 1.69 ng/ml) with the differences between these subjects becoming significant with age (p = 0.02). However, we found no correlation between sCTLA-4 levels and the CTLA-4 CT-60 SNP genotypes. Conclusion: Consistent with the higher serum sCTLA-4 levels observed in other autoimmune diseases, our results suggest that sCTLA-4 may be a risk factor for T1D. However, our results do not support the conclusion that the CT-60 SNP controls the expression of sCTLA-4.