0000000000121596
AUTHOR
N. Matheis
Das polyglanduläre Autoimmunsyndrom – Lebensqualität und familiäre Beteiligung
Hintergrund und Fragestellung: Fur Patienten mit einem Polyglandularem Autoimmunsyndrom (PGA) und ihre Angehorigen liegen keine Daten zur familiaren Beteiligung und zur Lebensqualitat vor. Daher erfolgte eine Erhebung in einer reprasentativen Gruppe. Patienten und Methoden: Im Rahmen einer prospektiv angelegten und kontrollierten Studie wurden klinische und serologische Untersuchungen an 75 konsekutiv aufgenommenen Patienten mit PGA (mittleres Alter 47,5 ± 15,3 Jahre; 65,3 % Frauen) mit 108 Angehorigen (mittleres Alter 33,13 Jahre ± 20,08 Jahre; 65,7% Frauen) durchgefuhrt. Drei validierte Messinstrumente (Short Form 36 [SF-36], Hospital Anxiety and Depression Scale [HADS] und Giesener Be…
Proteomics Differentiate Between Thyroid-Associated Orbitopathy and Dry Eye Syndrome.
PURPOSE: In patients with thyroid-associated orbitopathy (TAO), the dry eye syndrome occurs frequently, and symptoms and signs of both disorders overlap making early and accurate differential diagnosis difficult. A differentiation via specific markers is warranted. METHODS: Tear fluid samples of 120 subjects with TAO, TAO + dry eye, dry eye, and controls were collected. The samples were measured using matrix-assisted laser desorption ionization mass spectrometry. The identified proteins were tested with antibody microarrays. RESULTS: Proteomics identified deregulated proteins in TAO and dry eye. Compared with dry eye, proline-rich protein 1 (PROL1, P = 0.002); uridine diphosphate (UDP)-gluc…
Genome wide identification of new genes and pathways in patients with both autoimmune thyroiditis and type 1 diabetes
Autoimmune thyroid diseases (AITD) and Type 1 diabetes (T1D) frequently occur in the same individual pointing to a strong shared genetic susceptibility. Indeed, the co-occurrence of T1D and AITD in the same individual is classified as a variant of the autoimmune polyglandular syndrome type 3 (designated APS3v). Our aim was to identify new genes and mechanisms causing the co-occurrence of T1D + AITD (APS3v) in the same individual using a genome-wide approach. For our discovery set we analyzed 346 Caucasian APS3v patients and 727 gender and ethnicity matched healthy controls. Genotyping was performed using the Illumina Human660W-Quad.v1. The replication set included 185 APS3v patients and 340…
HLA Class II Differentiates Between Thyroid and Polyglandular Autoimmunity.
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) v…
Type 1 diabetes and polyglandular autoimmune syndrome: A review
Type 1 diabetes (T1D) is an autoimmune disorder caused by inflammatory destruction of the pancreatic tissue. The etiopathogenesis and characteristics of the pathologic process of pancreatic destruction are well described. In addition, the putative susceptibility genes for T1D as a monoglandular disease and the relation to polyglandular autoimmune syndrome (PAS) have also been well explored. The incidence of T1D has steadily increased in most parts of the world, especially in industrialized nations. T1D is frequently associated with autoimmune endocrine and non-endocrine diseases and patients with T1D are at a higher risk for developing several glandular autoimmune diseases. Familial cluster…
Proteomics of Orbital Tissue in Thyroid-Associated Orbitopathy.
A potentially altered protein expression profile in orbital tissue from patients with thyroid-associated orbitopathy (TAO) is suspected.To detect for the first time changes in proteomic patterns of orbital connective tissue in TAO and compare these with control tissue using mass spectrometry.Proteomics cross-sectional, comparative study.Two academic endocrine institutions.A total of 64 orbital and peripheral adipose tissue samples were collected from 39 patients with TAO and 25 control subjects.Samples were analyzed and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technology.Mean intensity values of all identified peptides per protein.Thirty-…
Proteomics of tear fluid in thyroid-associated orbitopathy.
Proteomics and mass spectrometry are useful tools for peptide screening in body fluids. In thyroid-associated orbitopathy (TAO), evidence for lacrimal gland involvement with altered composition of tears has been reported. Our objective was to detect and evaluate potential changes in the proteomic patterns of tear fluid in TAO.Tear fluid was collected from 45 patients with TAO and 15 healthy controls. Tear proteins were analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, and peptides were identified using matrix-assisted laser desorption/ionization time-of-flight technology.Peptides with molecular weights 3808 Dalton (Da, p=0.004), 3734 Da (p=0.034),…
Autoimmune polyglandular syndrome type 2 shows the same HLA class II pattern as type 1 diabetes†
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 APS type 2 had significantly more often the alleles DRB1*03 (P(c) < 0.0001), DRB1*04 (P(c) < 0.000005), DQA1*03 (P(c) < 0.0001), and DQB1*02 (P(c) < 0.05), when compared with controls. Less frequent…
HLA class II haplotypes differentiate between the adult autoimmune polyglandular syndrome types II and III.
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…
Prevalence, Phenotype, and Psychosocial Well-Being in Euthyroid/Hypothyroid Thyroid-Associated Orbitopathy.
At the onset of thyroid-associated orbitopathy (TAO), most patients are hyperthyroid, while scarce data are available on euthyroid/hypothyroid TAO. The aim of this study was to assess the prevalence, phenotype, and psychosocial burden of patients with initially euthyroid/hypothyroid TAO.The medical records of 461 consecutive and unselected patients with TAO followed at a specialized joint thyroid-eye clinic were analyzed within this retrospective cross-sectional study. Main outcome measures were the prevalence of initially eu- or hypothyroid TAO as well as ophthalmic signs and symptoms, disease-specific quality of life (QoL), work impairment, and rate of psychotherapy in initially eu-/hypot…