HLA Class II Haplotypes Differentiate Between the Adult Autoimmune Polyglandular Syndrome Types II and III

Published on Jan 1, 2014in The Journal of Clinical Endocrinology and Metabolism5.399
· DOI :10.1210/JC.2013-2852
Brigitte K. Flesch6
Estimated H-index: 6
(German Red Cross),
N. Matheis2
Estimated H-index: 2
(University of Mainz)
+ 3 AuthorsGeorge J. Kahaly64
Estimated H-index: 64
(University of Mainz)
Sources
Abstract
Background: Genetics of the adult autoimmune polyglandular syndrome (APS) is poorly understood. Aim: The aim of this study was to gain further insight into the genetics of the adult APS types. Site: The study was conducted at a university referral center. Methods: The human leukocyte antigen (HLA) class II alleles, haplotypes, and genotypes were determined in a large cohort of patients with APS, autoimmune thyroid disease (AITD), and type 1 diabetes and in healthy controls by the consistent application of high-resolution typing at a four-digit level. Results: Comparison of the allele and haplotype frequencies significantly discriminated patients with APS vs AITD and controls. The HLA class II alleles DRB1*03:01 *04:01, DQA1*03:01, *05:01, DQB1*02:01, and *03:02 were observed more frequently (P < .001) in APS than in AITD and controls, whereas the alleles DRB1*15:01, DQB1*03:01, and *06:02 were underrepresented in APS vs AITD (Pc < .001) and controls (Pc < .01), respectively. The DRB1*03:01-DQA1*05:01-DQB1...
📖 Papers frequently viewed together
References19
Newest
#1Ichiro Horie (Saga: Saga Group)H-Index: 13
#2Eiji Kawasaki (Nagasaki University)H-Index: 49
Last. Atsushi KawakamiH-Index: 60
view all 9 authors...
Objective: Type 1 diabetes (T1D) is commonly associated with autoimmune thyroid disease (AITD), and the occurrence of both T1D and AITD in a patient is defined as autoimmune polyglandular syndrome type 3 variant (APS3v). We aimed to clarify the differences in the clinical and genetic characteristics of APS3v patients and T1D patients without AITD [T1D/AITD(−)] in the Japanese population. Design/Patients: Our subjects were 54 APS3v patients and 143 T1D/AITD(−) patients who were consecutively diag...
Source
#1H. Fourati (University of Sfax)H-Index: 7
#2Nadia Mahfoudh (University of Sfax)H-Index: 10
Last. Hatem Masmoudi (University of Sfax)H-Index: 18
view all 12 authors...
Resume Objectifs L’objectif de notre etude etait de determiner les marqueurs HLA DR-DQ de susceptibilite et de protection dans une population tunisienne de malades atteints de polyendocrinopathies auto-immunes (PEA). Patients et methodes Soixante-deux malades non apparentes atteints de PEAII ( n = 20) et PEAIII ( n = 42) et 146 temoins sains non apparentes du sud tunisien ont ete genotypes pour les alleles HLA-DRB1* et HLA-DQB1* du gene HLA class II grâce a une technique de polymerase chain reac...
Source
#1C. Weinstock (German Red Cross)H-Index: 2
#2N. Matheis (University of Mainz)H-Index: 2
Last. G. J. Kahaly (University of Mainz)H-Index: 1
view all 8 authors...
Autoimmune polyglandular syndrome (APS) type 2 is defined by the manifestation of at least two autoimmune endocrine diseases. Only few data exist on genetic associations of APS type 2. In this controlled study, 98 patients with APS type 2, 96 patients with type 1 diabetes (T1D), and 92 patients with autoimmune thyroid disease, both as a single autoimmune endocrinopathy, were tested for association with alleles of the human leukocyte antigen (HLA) class II loci DRB1, DQA1, and DQB1. Patients with...
Source
#1Peter R. Baker (University of Colorado Denver)H-Index: 14
#2Erin E. Baschal (University of Colorado Denver)H-Index: 15
Last. George S. Eisenbarth (University of Colorado Denver)H-Index: 113
view all 12 authors...
Context: Multiple autoimmune disorders (e.g. Addison’s disease, type 1 diabetes, celiac disease) are associated with HLA-DR3, but it is likely that alleles of additional genes in linkage disequilibrium with HLA-DRB1 contribute to disease. Objective: The objective of the study was to characterize major histocompatability complex (MHC) haplotypes conferring extreme risk for autoimmune Addison’s disease (AD). Design, Setting, and Participants: Eighty-six 21-hydroxylase autoantibody-positive, nonaut...
Source
#1Francesca Menconi (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 23
#2Roman Osman (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 42
Last. Yaron Tomer (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 64
view all 6 authors...
There is strong genetic association between type 1A diabetes (T1D) and autoimmune thyroid disease (AITD). T1D and AITD frequently occur together in the same individual, a condition classified as a variant of the autoimmune polyglandular syndrome type 3 (APS3). Because T1D and AITD are individually strongly associated with different HLA class II sequences, we asked which HLA class II pocket sequence and structure confer joint susceptibility to both T1D and AITD in the same individual (APS3v). We ...
Source
#1Manuela Dittmar (CAU: University of Kiel)H-Index: 8
#2George J. KahalyH-Index: 64
Background: Autoimmune thyroid diseases (AITD) and type 1 diabetes (T1D) are the most common autoimmune endocrine disorders. They occur frequently together in the same individual. This disease combination is denominated as autoimmune polyglandular syndrome type 3 variant (APS3v). This review aims to describe the genetic and pathological background of the syndrome. The joint susceptibility genes for AITD and T1D as well as the underlying pathogenetic mechanisms contributing to the development of ...
Source
#1Kaspar Sørensen (Copenhagen University Hospital)H-Index: 30
#2Lise Aksglaede (Copenhagen University Hospital)H-Index: 39
Last. Anders Juul (Copenhagen University Hospital)H-Index: 96
view all 4 authors...
Context: In the 1990s, the American population-based study NHANES III renewed the focus on possible secular trends in male puberty. However, no conclusions could be made on pubertal onset due to the lack of compatible data. Objective: The aim of the study was to evaluate secular trends in pubertal onset during the recent 15 yr and their relation to body mass index (BMI) in boys. Design and Setting: We conducted a cross-sectional study in 1991–1993 and a combined cross-sectional and longitudinal ...
Source
Background In recent years, scientific knowledge pertaining to the rare ORPHAN polyglandular autoimmune syndrome (registered code ORPHA 282196) has accumulated.
Source
#1Maria Justina B. Villano (University of Cincinnati Academic Health Center)H-Index: 1
#2Amanda K. Huber (University of Cincinnati Academic Health Center)H-Index: 5
Last. Yaron Tomer (University of Cincinnati Academic Health Center)H-Index: 64
view all 6 authors...
Context: Epidemiological data support a shared genetic susceptibility to autoimmune thyroid disease (AITD) and type 1 diabetes (T1D). Both diseases frequently occur within the same family and in the same individual. Patients developing both T1D and AITD are considered to have an autoimmune polyglandular syndrome type 3 variant (APS3v). Objective: The goals of this study were to identify the joint susceptibility loci/genes for T1D and AITD. Settings: The study was conducted at an academic medical...
Source
#1Manuela DittmarH-Index: 17
#2Maximilian IdeH-Index: 2
Last. George J. Kahaly (University of Mainz)H-Index: 64
view all 4 authors...
Objectives: Polyglandular failure or autoimmunity (PGA) involves at least two endocrine diseases. Several genes may play a role in its etiology. This study analyzed 1) whether HLA-DRB1, HLA-DQB1, and MHC class I chain-related gene A (MICA) polymorphisms are associated in PGA and 2) whether PGA patients display stronger associations with these immune genes than patients with monoglandular autoimmunity (MGA). Design: Association study. Methods: HLA-DRB1, HLA-DQB1, and MICA alleles were analyzed in...
Source
Cited By29
Newest
#1Marta Fichna (Poznan University of Medical Sciences)H-Index: 13
#2Magdalena Żurawek (PAN: Polish Academy of Sciences)H-Index: 9
Last. Marek Ruchała (Poznan University of Medical Sciences)H-Index: 22
view all 9 authors...
Genetically predisposed individuals may develop several autoimmune diseases—autoimmune polyendocrine syndromes (APS). APS types 2–4, are complex disorders, which combine various organ-specific autoimmune conditions. Recent reports support the considerable role of the BACH2 gene in immune cell differentiation and shifting the T-cell balance towards regulatory T-cells. BACH2 polymorphisms are associated with autoimmune disorders, including Addison’s disease (AD), Graves’ disease (GD), and probably...
Source
#2Anna A. LarinaH-Index: 1
Last. Diana A DimitrovaH-Index: 1
view all 5 authors...
Autoimmune polyendocrine syndromes (APS) are a heterogeneous group of diseases characterized by the presence of autoimmune dysfunction of 2 or more endocrine glands and other non-endocrine organs. ...
Source
#1Lara Frommer (University of Mainz)H-Index: 7
#2George J. Kahaly (University of Mainz)H-Index: 64
Type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) are the most frequent chronic autoimmune diseases worldwide. Several autoimmune endocrine and non-endocrine disorders tend to occur together. T1D and AITD often cluster in individuals and families, seen in the formation of autoimmune polyendocrinopathy (AP). The close relationship between these two diseases is largely explained by sharing a common genetic background. The HLA antigens DQ2 (DQA1*0501-DQB1*0201) and DQ8 (DQA1*0301-DQB1*030...
Source
#1Lara Frommer (University of Mainz)H-Index: 7
#2Brigitte K. Flesch (German Red Cross)H-Index: 6
Last. George J. Kahaly (University of Mainz)H-Index: 64
view all 4 authors...
CONTEXT: The structure of the human leucocyte antigen (HLA) peptide-binding clefts strongly contributes to monoglandular and polyglandular autoimmunity (AP). OBJECTIVE: To investigate the impact of amino acid polymorphisms on the peptide-binding interactions within HLA class II and its association with AP. DESIGN: Immunogenetic study. SETTING: Tertiary referral center for autoimmune endocrine diseases. SUBJECTS: 587 subjects with AP, autoimmune thyroid disease (AITD), type 1 diabetes (T1D), and ...
Source
Background Autoimmune polyglandular syndrome type II (APS II) is defined as the combination of autoimmune adrenal insufficiency and autoimmune thyroid disease (AITD) and/or type I diabetes mellitus (T1DM) in the same patient. Case presentation A 15-year-old boy had a history of weight loss, nausea and vomiting, headache, restlessness, and tanned skin. He was diagnosed with Graves' disease. Two weeks after carbimazol therapy was commenced, he presented with adrenal crises (fever, arterial hypoten...
Source
#1Sari Mäkimattila (UH: University of Helsinki)H-Index: 30
#2Valma HarjutsaloH-Index: 24
Last. Per-Henrik GroopH-Index: 82
view all 4 authors...
OBJECTIVE The aim of this study was to quantify the excess risk of autoimmune hypothyroidism and hyperthyroidism, Addison disease, celiac disease, and atrophic gastritis in adults with type 1 diabetes (T1D) compared with nondiabetic individuals in Finland. RESEARCH DESIGN AND METHODS The study included 4,758 individuals with T1D from the Finnish Diabetic Nephropathy (FinnDiane) Study and 12,710 nondiabetic control individuals. The autoimmune diseases (ADs) were identified by linking the data wit...
Source
#1Shiyuan Tian (JLU: Jilin University)
#2Baofeng Xu (JLU: Jilin University)H-Index: 8
Last. Rui Liu (JLU: Jilin University)H-Index: 2
view all 4 authors...
RATIONALE: Polyglandular autoimmune syndromes (PAS) are a heterogeneous group of rare diseases characterized by the association of at least 2 organ-specific autoimmune disorders, concerning both the endocrine and nonendocrine organs. Type III is defined as the combination of autoimmune thyroid disease and other autoimmune conditions (other than Addison disease), and is divided into 4 subtypes. We describe a patient with Hashimoto thyroiditis, adult-onset Still disease, alopecia, vasculitis, anti...
Source
Autoimmune polyglandular diseases (APD) are defined as the presence of two autoimmune –induced endocrine failures. With respect to the significant morbidity and potential mortality of APD, the diagnostic objective is to detect APD at an early stage, with the advantage of less frequent complications, effective therapy and better prognosis. This requires that patients at risk be regularly screened for subclinical endocrinopathies prior to clinical manifestation. Regarding the time interval between...
Source
#1Tomoyo Mifune-Morioka (Okayama University)
#2Haruhito A. Uchida (Okayama University)H-Index: 15
Last. Jun WadaH-Index: 63
view all 19 authors...
Eight years prior to her present admission, a 61-year-old Japanese woman was diagnosed with autoimmune hepatitis, slowly progressive insulin-dependent diabetes mellitus, and chronic thyroiditis; she had been treated with oral prednisolone (PSL). After she suddenly discontinued PSL, she newly developed systemic lupus erythematosus. A combination therapy of oral PSL and intravenous cyclophosphamide resulted in remission. She was finally diagnosed with autoimmune polyglandular syndrome (APS) type 3...
Source
#1Bernadette Biondi (University of Naples Federico II)H-Index: 58
#2George J. Kahaly (University of Mainz)H-Index: 64
Last. R. Paul Robertson (UW: University of Washington)H-Index: 51
view all 3 authors...
: Thyroid dysfunction and diabetes mellitus are closely linked. Several studies have documented the increased prevalence of thyroid disorders in patients with diabetes mellitus and vice versa. This review critically discusses the different underlying mechanisms linking type 1 and 2 diabetes and thyroid dysfunction to demonstrate that the association of these two common disorders is unlikely a simple coincidence. We assess the current state of knowledge on the central and peripheral control of th...
Source
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.