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This Article Full Text Full Text (PDF) All Versions of this Article: EJE-09-0600v1 161/5/787    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Daroszewski, J. Articles by Bolanowski, M. PubMed PubMed Citation Articles by Daroszewski, J. Articles by Bolanowski, M.

Soluble CTLA-4 receptor an immunological marker of Graves' disease and severity of ophthalmopathy is associated with CTLA-4 Jo31 and CT60 gene polymorphisms

Department of Endocrinology, Diabetology, and Isotope Therapy, Medical University, ul. Pasteura 4, 50-367 Wroclaw, Poland¹ Laboratory of Immunopathology, Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. Weigla 12, 53-114 Wroclaw, Poland² Department of Hematology, Blood Neoplastic Diseases, and Bone Marrow Transplantation, Medical University, ul. Pasteura 4, 50-367 Wroclaw, Poland³ Department of Forensic Medicine, Medical University, ul. Curie-Sklodowskiej, 52, 50-368 Wroclaw, Poland⁴ Department of Ophthalmology, Medical University, ul. Chalubinskiego 2a, 50-368 Wroclaw, Poland

(Correspondence should be addressed to E Pawlak; Email: epawlak{at}iitd.pan.wroc.pl)

(J Daroszewski and E Pawlak contributed equally to this work)

Objective: Graves' disease (GD) is an autoimmune disorder with genetic and environmental background. CTLA-4 is a candidate gene for thyroid autoimmunity. Increased serum levels of soluble CTLA-4 (sCTLA-4) were found in some autoimmune diseases.

Aim: The aim of the study was to evaluate the relation between sCTLA-4 level and clinical manifestation of Graves' ophthalmopathy (GO), thyroid status, and CTLA-4 gene polymorphisms.

Design: Serum sCTLA-4 concentrations were determined in 93 GO patients and 93 healthy controls. In the GO group, CTLA-4 gene was genotyped in five polymorphic sites: g.319C>T, c.49A>G, CT60 by means of PRC-RFLP, Jo31, and g.*642AT(8_33) by means of minisequencing assay.

Results: Serum sCTLA-4 level was significantly higher in the GO group than in controls (median: 7.94 vs 0.00 ng/ml, P=0.000001). This level was higher in severe than in nonsevere GO (median: 10.3 vs 5.6 ng/ml, P=0.01). sCTLA-4 concentration was related neither to the activity of GO nor to thyroid function. Elevated sCTLA-4 levels were observed in carriers Jo31[G] allele (genotype GG+GT) as compared with subjects with an absence of the [G] allele (TT genotype; median: 9.18 vs 4.0 ng/ml, P=0.02). Also patients possessing CT60[G] allele (genotype GG+GA) had higher serum sCTLA-4 levels than subjects who lack the [G] allele (AA genotype; median: 8.73 vs 2.28 ng/ml, P=0.03).

Conclusions: It was shown for the first time that increased serum concentration of sCTLA-4 correlate with the severity of GO. Genetic variation in the CTLA-4 gene region in GD patients at least partially determines the level of sCTLA-4.