scholarly journals Monocytic Cytokines in Autoimmune Polyglandular Syndrome Type 2 Are Modulated by Vitamin D and HLA-DQ

2020 ◽  
Vol 11 ◽  
Author(s):  
Anna U. Kraus ◽  
Marissa Penna-Martinez ◽  
Firouzeh Shoghi ◽  
Gesine Meyer ◽  
Klaus Badenhoop
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
High Risk ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Autoimmune Polyglandular Syndrome ◽  
Pathway Gene ◽  
Hla Dq

ContextAutoimmune polyglandular syndrome (APS-2: autoimmune Addison’s disease or type 1 diabetes) is conferred by predisposing HLA molecules, vitamin D deficiency, and heritable susceptibility. Organ destruction is accompanied by cytokine alterations. We addressed the monocytic cytokines of two distinct APS-2 cohorts, effects of vitamin D and HLA DQ risk.MethodsAPS-2 patients (n = 30) and healthy controls (n = 30) were genotyped for HLA DQA1/DQB1 and their CD14+ monocytes stimulated with IL1β and/or 1,25(OH)2D3 for 24 h. Immune regulatory molecules (IL-6, IL-10, IL-23A, IL-15, CCL-2, PD-L1), vitamin D pathway gene transcripts (CYP24A1, CYP27B1, VDR), and CD14 were analyzed by enzyme-linked immunosorbent assay and RTqPCR.ResultsPro-inflammatory CCL-2 was higher in APS-2 patients than in controls (p = 0.001), whereas IL-6 showed a trend – (p = 0.1). In vitro treatment with 1,25(OH)2D3 reduced proinflammatory cytokines (IL-6, CCL-2, IL-23A, IL-15) whereas anti-inflammatory cytokines (IL-10 and PD-L1) rose both in APS-type 1 diabetes and APS-Addison´s disease. Patients with adrenal autoimmunity showed a stronger response to vitamin D. Expression of IL-23A and vitamin D pathway genes VDR and CYP27B1 varied by HLA genotype and was lower in healthy individuals with high-risk HLA (p = 0.0025; p = 0.04), while healthy controls with low-risk HLA showed a stronger IL-10 and CD14 expression (p = 0.01; p = 0.03).Conclusion1,25(OH)2D3 regulates the monocytic response in APS-2 disorders type 1 diabetes or Addison´s disease. The monocytic cytokine profile of individuals carrying HLA high-risk alleles is proinflammatory, enhances polyglandular autoimmunity and can be targeted by vitamin D.

scholarly journals Type 1 Diabetes Mellitus Donor Mesenchymal Stromal Cells Exhibit Comparable Potency to Healthy Controls In Vitro

2016 ◽  
Vol 5 (11) ◽  
pp. 1485-1495 ◽  
Author(s):  
Lindsay C. Davies ◽  
Jessica J. Alm ◽  
Nina Heldring ◽  
Guido Moll ◽  
Caroline Gavin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Healthy Controls

Vitamin D supplementation induces CatG-mediated CD4+ T cell inactivation and restores pancreatic beta-cell function in mice with type 1 diabetes

2021 ◽  
Author(s):  
Xiaoyang Lai ◽  
Xuyang Liu ◽  
Xia Cai ◽  
Fang Zou
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Beta Cell ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Β Cell Function

Type 1 diabetes (T1D) is a chronic autoimmune disease accompanied by the immune-mediated destruction of pancreatic β-cells. In this study, we aimed to explore the regulatory effects of Vitamin D (VD) supplementation on pancreatic β-cell function by altering the expression of bioinformatically identified cathepsin G (CatG) in T1D model mice. A T1D mouse model was established in non-obese diabetic (NOD) mice, and their islets were isolated and purified. Pancreatic mononuclear cells (MNCs) were collected, from which CD4+ T cells were isolated. The levels of interleukin (IL)-2, IL-10, tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ) in the supernatant of mouse pancreatic tissue homogenate were assessed using ELISA. Immunohistochemistry and TUNEL staining were conducted to evaluate the effects of VD supplementation on pancreatic tissues of T1D mice. The pancreatic beta-cell line MIN6 was used for in vitro substantiation of findings in vivo. VD supplementation reduced glucose levels and improved glucose tolerance in T1D mice. Further, VD supplementation improved pancreatic β-cell function and suppressed immunological and inflammatory reactions in the T1D mice. We documented overexpression of CatG in diabetes tissue samples, and then showed that VD supplementation normalized the islet immune microenvironment through down-regulating CatG expression in T1D mice. Experiments in vitro subsequently demonstrated that VD supplementation impeded CD4+ T activation by down-regulating CatG expression, and thereby enhanced pancreatic β-cell function. Results of the present study elucidated that VD supplementation can down-regulate the expression of CatG and inhibit CD4+ T cell activation, thereby improving β-cell function in T1D.

scholarly journals The High-Risk Type 1 Diabetes HLA-DR and HLA-DQ Polymorphisms Are Differentially Associated With Growth and IGF-I Levels in Infancy: The Cambridge Baby Growth Study

Diabetes Care ◽  
2021 ◽  
pp. dc202820
Author(s):  
Antigoni Eleftheriou ◽  
Clive J. Petry ◽  
Ieuan A. Hughes ◽  
Ken K. Ong ◽  
David B. Dunger
Keyword(s):  
Type 1 Diabetes ◽  
High Risk ◽  
Growth Study ◽  
Hla Dr ◽  
Hla Dq ◽  
Igf I ◽  
High Risk Type

scholarly journals Vitamin D 1alpha-hydroxylase (CYP1alpha) polymorphism in Graves' disease, Hashimoto's thyroiditis and type 1 diabetes mellitus

2002 ◽  
pp. 777-781 ◽  
Author(s):  
MA Pani ◽  
K Regulla ◽  
M Segni ◽  
M Krause ◽  
S Hofmann ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Vitamin D ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Hashimoto’S Thyroiditis ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Hla Dq ◽  
Hla Dq2

OBJECTIVE: The vitamin D endocrine system plays a role in the regulation of (auto)immunity and cell proliferation. Vitamin D 1alpha-hydroxylase (CYP1alpha) is one of the key enzymes regulating both systemic and tissue levels of 1,25-dihyroxyvitamin D(3) (1,25(OH)(2)D(3)). Administration of 1,25(OH)(2)D(3), whose serum levels were found to be reduced in type 1 diabetes and thyroid autoimmunity, prevents these diseases in animal models. We therefore investigated a recently reported CYP1alpha polymorphism for an association with type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis. DESIGN AND METHODS: Four hundred and seven Caucasian pedigrees with one offspring affected by either type 1 diabetes (209 families), Graves' disease (92 families) or Hashimoto's thyroiditis (106 families) were genotyped for a C/T polymorphism in intron 6 of the CYP1alpha gene on chromosome 12q13.1-13.3 and transmission disequilibrium testing (TDT) was performed. Subsets of affected offspring stratified for HLA-DQ haplotype were compared using chi(2) testing. RESULTS: There was no deviation from the expected transmission frequency in either type 1 diabetes mellitus (P=0.825), Graves' disease (P=0.909) or Hashimoto's thyroiditis (P=0.204). However, in Hashimoto's thyroiditis the CYP1alpha C allele was significantly more often transmitted to HLA-DQ2(-) patients (27 transmitted vs 14 not transmitted; TDT: P=0.042) than expected. The C allele was less often transmitted to HLA-DQ2(+) patients (9 transmitted vs 12 not transmitted; TDT: P=0.513), although the difference was not significant (chi(2) test: P=0.143). A similar difference was observed in type 1 diabetes between offspring with high and low risk HLA-DQ haplotypes (chi(2) test: P=0.095). CONCLUSIONS: The CYP1alpha intron 6 polymorphism appears not to be associated with type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis. A potential association in subsets of patients with type 1 diabetes and Hashimoto's thyroiditis should be further investigated as well as its functional implications.

scholarly journals Zinc transporter 8 autoantibody in the diagnosis of type 1 diabetes in children

2020 ◽  
Vol 63 (10) ◽  
pp. 402-405
Author(s):  
Nur Rochmah ◽  
Muhammad Faizi ◽  
Siti Wahyu Windarti
Keyword(s):  
Type 1 Diabetes ◽  
Glycosylated Hemoglobin ◽  
Hemoglobin Concentration ◽  
Zinc Transporter ◽  
Autoimmune Response ◽  
Enzyme Linked Immunosorbent Assay ◽  
Specific Gene ◽  
Healthy Controls ◽  
Zinc Transporter 8

Background: Type 1 diabetes (T1D) is an organ-specific autoimmune disease related to the autoimmune response against pancreatic β-cells. Zinc transporter 8 (ZnT8), an islet-specific gene product localized to the β-cell insulin granule, was recently identified as an autoantigen in T1D.Purpose: To evaluate the use of ZnT8 autoantibody (ZnT8A) for diagnosing T1D.Methods: This case-control study was conducted at Dr. Soetomo General Hospital, Surabaya, Indonesia, from March to May 2019. Children younger than 18 years of age with T1D based on the International Society for Pediatric and Adolescent Diabetes guideline and healthy controls were included. We measured ZnT8A level using enzyme-linked immunosorbent assay (cutoff value, 0.315).Results: There were 30 children with T1D (50.0% boys; mean age, 11.3±3.7 years) and 18 healthy controls (44.4% boys; mean age, 8.3±3.1 years); 1 patient in each group was Madurese, while the others were Javanese. Twenty-two of 30 subjects with T1D (73.3%) tested positive for ZnT8A compared to 5 of 18 controls (27.8%) (<i>P</i>=0.02; odds ratio, 7.15; 95% confidence interval, 1.93–26.52). When ZnT8A-positive and -negative T1D cases were compared, no differences were detected in age at diagnosis, duration of diabetes, presence of ketoacidosis, body mass index, glycosylated hemoglobin concentration, or C-peptide concentrations.Conclusion: ZnT8A may be useful in the diagnosis of T1D.

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