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

• Published in: European journal of endocrinology Vol. 161; no. 5; pp. 787 - 793
• Main Authors: Daroszewski, Jacek, Pawlak, Edyta, Karabon, Lidia, Frydecka, Irena, Jonkisz, Anna, Slowik, Miroslaw, Bolanowski, Marek
• Format: Journal Article
• Language: English
• Published: Bristol BioScientifica 01.11.2009
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, CD - blood; Antigens, CD - genetics; Antigens, CD - immunology; Biological and medical sciences; Clinical Study; Cohort Studies; CTLA-4 Antigen; DNA - chemistry; DNA - genetics; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Genetic Variation; Genotype; Graves Ophthalmopathy - blood; Graves Ophthalmopathy - genetics; Graves Ophthalmopathy - immunology; Humans; Male; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Statistics, Nonparametric; Thyroid. Thyroid axis (diseases); Thyrotropin - blood; Thyroxine - blood; Triiodothyronine - blood; Vertebrates: endocrinology; Young Adult; Endocrinopathy; Immunopathology; Genetic variability; Hyperthyroidism; Thyroid diseases; Biological marker; Autoimmune disease; Genotype; Soluble form; Eye disease; Association; Graves disease; Phenotype variation; Endocrinology; Polymorphism; Biological receptor
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/EJE-09-0600

ObjectiveGraves' 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.AimThe 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.DesignSerum 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.ResultsSerum 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).ConclusionsIt 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.