Yersinia infections and Graves’ disease

L. Khamnueva, T. V. Goma, V. Klimov
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Abstract

Background. The most common thyroid disease, accompanied by thyrotoxicosis syndrome, is Graves' disease (GD). Information about the role of Yersinia in the development of this disease is contradictory. Aims. To study the significance of Yersinia (Y.) enterocolitica and Y. pseudotuberculosis in the development of Graves' disease. Materials and methods. 78 patients with GD. Identification of antibodies to Y. was carried out by the following methods: 1. agglutination test (AT) with suspensions of live virulent cultures Y. pseudotuberculosis, Y. enterocolitica O:3 and O:9; 2. indirect hemagglutination test (IHET) with the use of erythrocyte diagnosticum; 3. determination of IgA and IgG antibodies against pathogenicity factors of Y. enterocolitica strains by immunoblotting (30 patients with GD). Results. Diagnostically significant titers of antibodies to Y. pseudotuberculosis and Y. enterocolitica were obtained in all patients with GD by AT. The greatest total thyroid volume determined by ultrasound investigation (p = 0.010) and the maximum duration of the disease (p = 0.040) were determined in the group of patients with the maximum antibody titer. No significant relation was found between the titer of antibodies to Yersinia and the levels of thyroid hormones stimulating the thyroid antibodies.The test for detection of IgA antibodies by immunoblotting was negative in 30 patients with GD (9 patients with a titer of antibodies by AT 1:800 – 1:1600, 17 – 1:400, 4 – 1:200). In all cases with the maximum antibody titer in AT, the positive IgG antibodies to the antigens YopM (Yop2a), YopH (Yop2b), V-antigen, YopD were found. The GD duration in patients with negative titers of antibodies by the immunoblotting test was less than with the positive one (p = 0.010). The privative clinical and anamnestic data and negative results by IHET confirmed the absence of active and/or transferred Yersinia infections in all the examined patients with GD. Conclusions. The cross-reacting antibodies to the antigens of Y. enterocolitica are determined in the serum of GD patients by AT and immunoblotting. The diagnostic titer of these antibodies is more often detected in patients with greater GD duration and larger volume of the thyroid gland. The absence of a link between the titer of these antibodies and the levels of thyroid hormones, the antibodies to the thyrotropin receptors of pituitary, as well as negative results by IHET with a diagnosticum that does not contain outer membrane proteins of pathogenic Yersinia, deny the trigger role of Yersinia infections as an initiating factor in the development of GD.
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耶尔森氏菌感染和格雷夫斯病
背景。最常见的甲状腺疾病,伴甲状腺毒症,是格雷夫斯病(GD)。关于耶尔森菌在该病发展中的作用的信息是相互矛盾的。目标探讨小肠结肠炎耶尔森菌和假结核耶尔森菌在Graves病发病中的意义。材料和方法。78例GD患者。采用以下方法鉴定Y.;假结核耶氏菌、小肠结肠炎耶氏菌O:3和O:9的活毒力培养菌悬液凝集试验(AT);2. 间接血凝试验(IHET)与红细胞诊断仪的应用;3.免疫印迹法测定30例GD患者小肠结肠炎致病性因子IgA和IgG抗体。结果。在所有GD患者中,通过AT检测获得了具有诊断意义的假结核耶氏菌和小肠结肠炎耶氏菌抗体滴度。抗体滴度最高组的甲状腺总容积最大(p = 0.010),病程最长(p = 0.040)。耶尔森氏菌抗体滴度与促甲状腺抗体的甲状腺激素水平无显著关系。30例GD患者免疫印迹法检测IgA抗体均为阴性(9例抗体滴度为AT:800 ~ 1:16 00,17 ~ 1:40 00,4 ~ 1:20 00)。在所有AT抗体滴度最高的病例中,均发现针对抗原YopM (Yop2a)、YopH (Yop2b)、v抗原、YopD的IgG抗体阳性。免疫印迹试验抗体滴度阴性患者的GD持续时间短于抗体滴度阳性患者(p = 0.010)。缺乏临床和记忆数据以及IHET阴性结果证实,所有GD患者均没有活动性和/或转移性耶尔森菌感染。结论。采用免疫印迹法检测GD患者血清中小肠结肠炎耶氏菌抗原的交叉反应抗体。这些抗体的诊断滴度通常在GD持续时间较长和甲状腺体积较大的患者中检测到。这些抗体滴度与甲状腺激素水平、垂体促甲状腺素受体抗体之间缺乏联系,以及IHET诊断结果阴性,诊断结果不含致病性耶尔森氏菌外膜蛋白,否认耶尔森氏菌感染作为GD发展的启动因素的触发作用。
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