Kanga U, Tandon N, Marwaha R K, Khanna R, Bhattacharya B, Singh S, Kumar N, Mehra N K
Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.
Clin Endocrinol (Oxf). 2006 May;64(5):573-9. doi: 10.1111/j.1365-2265.2006.02511.x.
Autoimmune thyroid diseases (AITD) encompass a number of conditions that have in common cellular and humoral responses targeting the thyroid gland. Interactions between susceptibility genes and environmental triggers are thought to initiate an autoimmune response to thyroid antigens leading to disease manifestation. Commencement of the disease in childhood leads to the presumption that genetics may have an important role in the causation of the disease.
The present study was aimed at evaluating the human leucocyte antigen (HLA) encoded susceptibility to develop juvenile autoimmune thyroiditis (JAT) in patients from North India.
We studied 48 consecutive patients of JAT along with 176 first-degree relatives for their thyroid function (FT4, TSH) and anti-thyroid peroxidase antibody status (AbTPO).
HLA studies were carried out using serology for HLA-class I antigens and DNA analysis of HLA-class II alleles. The data were compared with a cohort of 308 ethnically matched healthy individuals.
We observed overt hypothyroidism in 50% and AbTPO positivity in 70.8% of the index cases. Among the first-degree relatives, goitre was observed in 51.7%, thyroid dysfunction in 28.4% and AbTPO in 29.5% of individuals. Of the 37 relatives who underwent fine-needle aspiration cytology (FNAC), 60% had evidence of chronic lymphocytic thyroiditis (CLT). A strong positive association of HLA-DRB11404 was observed with the JAT (35.4%vs. 10.4%, chi2 = 19.8, Pc = 0.0001). We also observed a higher (72%, P = 0.03) paternal transmission of HLA-DRB11404 to affected offspring in comparison to unaffected offspring. HLA-DRB1*03 was also increased among JAT patients but did not reach statistical significance.
These studies point towards an important role of immune modifying genes, such as HLA, in influencing susceptibility to juvenile-onset AITD.
自身免疫性甲状腺疾病（AITD）包括多种疾病，这些疾病的共同特点是针对甲状腺的细胞和体液免疫反应。易感基因与环境触发因素之间的相互作用被认为会引发针对甲状腺抗原的自身免疫反应，从而导致疾病表现。疾病在儿童期开始发作，这使得人们推测遗传因素可能在疾病的病因中起重要作用。
本研究旨在评估印度北部患者中人类白细胞抗原（HLA）编码的易患青少年自身免疫性甲状腺炎（JAT）的情况。
我们研究了48例连续的JAT患者以及176名一级亲属的甲状腺功能（FT4、TSH）和抗甲状腺过氧化物酶抗体状态（AbTPO）。
使用血清学方法对HLA - I类抗原进行HLA研究，并对HLA - II类等位基因进行DNA分析。将数据与308名种族匹配的健康个体组成的队列进行比较。
我们观察到，在索引病例中，50%有明显的甲状腺功能减退，70.8%的AbTPO呈阳性。在一级亲属中，51.7%的个体有甲状腺肿大，28.4%的个体有甲状腺功能障碍，29.5%的个体有AbTPO。在接受细针穿刺细胞学检查（FNAC）的37名亲属中，60%有慢性淋巴细胞性甲状腺炎（CLT）的证据。观察到HLA - DRB11404与JAT有很强的正相关性（35.4%对10.4%，卡方 = 19.8，Pc = 0.0001）。与未受影响的后代相比，我们还观察到HLA - DRB11404从父亲向受影响后代的传递率更高（72%，P = 0.03）。JAT患者中HLA - DRB1*03也有所增加，但未达到统计学意义。
这些研究表明免疫调节基因，如HLA，在影响青少年型AITD的易感性方面起着重要作用。
