HLA Class II Differentiates Between Thyroid and Polyglandular Autoimmunity

Abstract

The HLA class II genes are susceptibility genes for autoimmune endocrine diseases; however, scarce data are available pertaining to the determinants of genetic susceptibility to polyglandular autoimmunity (PGA). A total of 300 consecutive and unselected patients with either PGA or monoglandular autoimmune thyroid disease (AITD) and 100 healthy control subjects were genotyped for the HLA class II DRB1, -DQA1, and -DQB1 alleles. Compared to patients with AITD and controls, the HLA-DRB1*03 (pc =0.001), *04 (pc<0.001), -DQA1*03 (pc<0.001), and -DQB1*02 (pc =0.001) alleles were increased in patients with PGA. When dividing patients with Hashimoto's thyroiditis (HT) into those with PGA (PGA-HT) vs. those with HT as monoglandular disease, significant differences for the DRB1*03 (pc=0.001) and DQA1*03 (pc=0.001) alleles were observed. In contrast, the DQB1*02 allele was more prevalent in PGA patients with Graves' disease (PGA-GD) vs. those with monoglandular GD (pc=0.002). The HLA-DRB1*15 (pc =0.001), -DQA1*01 (pc =0.001), -DQB1*05 (pc =0.002) and -DQB1*06 (pc =0.002) alleles were significantly less present in PGA compared to monoglandular AITD and controls, thus indicating protective alleles. The HLA class II alleles differentiate between mono- and polyglandular autoimmunity in patients with autoimmune thyroid disease.

Polyglandular autoimmune syndromes

“…Furthermore, several polymorphisms carry susceptibility for PAS. Immunogenetics and epidemiologic patterns differentiate between both mono-and polyglandular autoimmunity as well as between the subgroups of adult PAS types [32,33]. Further environmental risk factors i.e., nicotine consumption, infections or hormonal influence have been postulated.…”

“…Several polymorphisms have been reported as susceptibility genes and others are assumed to be involved. Genes that have already been identified to confer susceptibility encompass several HLA class I and II alleles which show concordant influence on both mono-and polyglandular autoimmunopathies but simultaneously differentiate between PAS types II and III [32,33,37]. In addition, the HLA genes on chromosome 6 have the highest implications.…”

Thyrotropin Receptor Blocking Antibodies

“…Autoimmune thyroid diseases (AITD) are characterized through increased familial clustering, reduced DNASE1 gene expression, CTLA-4 polymorphisms, and are strongly associated with the major histocompatibility (MHC) complex 1 2 3 4 . However, autoantibodies to various thyroid antigens are the most important biomarkers that are used to differentiate AITD from other thyroid conditions.…”

Human Leukocyte Antigen (HLA) Typing Study Identifies Maternal DQ2 Susceptibility Alleles among Infertile Women: Potential Associations with Autoimmunity and Micronutrients

“…Moreover, anti-thyroid antibodies interact with placental hormones, especially with chorionic gonadotropin and with chorionic thyrotropin, leading to an alteration of their function [ 52 , 54 ]. Thyroid disorders, both autoimmunity and/or dysfunction, may also be considered as a detectable marker of maternal immunological alterations, given the associations between thyroid homeostasis and immune abnormalities [ 52 , 53 , 54 , 55 , 56 ]. Micronutrients, including 25(OH)D, VB12, folic acid, and iron are often found to be deficient in AITD, resulting in malfunctioning of the thyroid.…”