TY  - JOUR
A1  - Kraus, Anna U.
A1  - Penna Martinez, Marissa
A1  - Shoghi, Firouzeh
A1  - Meyer, Gesine
A1  - Badenhoop, Klaus
T1  - Monocytic cytokines in autoimmune polyglandular syndrome type 2 are modulated by vitamin D and HLA-DQ
T2  - Frontiers in immunology
N2  - Context: Autoimmune 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.
Methods: APS-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. Results: Pro-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). Conclusion: 1,25(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.
KW  - Addison’s disease
KW  - type 1 diabetes
KW  - autoimmune thyroiditis
KW  - autoimmune polyglandular syndrome type 2
KW  - cytokine gene expression
KW  - HLA DQ haplotypes
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/57555
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-575559
SN  - 1664-3224
N1  - This work was supported by the Else Kröner-Fresenius Foundation (EKFS), Research Training Group Translational Research Innovation-Pharma (TRIP) and project funds from the German Diabetes Society (Deutsche Diabetes Gesellschaft-DDG).
VL  - 11
IS  - art. 583709
SP  - 1
EP  - 11
PB  - Frontiers Media
CY  - Lausanne
ER  -