Genetic risk for co‐occurrence of type 1 diabetes and celiac disease is modified byHLA‐C and killer immunoglobulin‐like receptors

Abstract

The prevalence of celiac disease (CD) in patients with type 1 diabetes (T1D) has been reported to be 5-7 times higher than in the general population. Risk factors for co-occurrence of both diseases have not been entirely established. The aim of our study was to analyze possible impact of human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptors (KIRs) on the co-occurrence of T1D and CD. We analyzed 67 patients with T1D, 68 patients with CD, 69 patients with both diseases (T1D+CD) and 130 controls. Statistical analysis was based on two tailed Fisher exact test with corrections for multiple testing. After stratification by DR3-DQ2, an association of HLA class I part of the COX haplotype (A1-B8-Cw7-DR3-DQ2) was not observed with each of the studied diseases separately, but it could be shown in case of the co-occurrence of T1D and CD. Only in the group of patients with coexisting diseases, the presence of HLA-C*07 (P = 8.65×10(-3) ) and HLA-B*08 (P = 0.03) but not HLA-A*01 increased the succeptibility. Our current data indicated that C*07, contributing C1 ligand (Pc = 3.67×10(-5) ) rather than B*08, that possesses no KIR ligand, could have an impact on the innate immunity rout of this susceptibility. The significant combination of C1-KIR2DL3 (Pc = 1.97×10(-4) ) observed in patients with coexisting diseases supports this hypotesis. Interestingly, no association was observed when C1 in combination with its stronger inhibitory receptor KIR2DL2 was investigated. Predominantly, weak inhibition in patients with coexisting T1D and CD could lead to a natural killer cell response, making them vulnerable for developing more than one autoimmune disease.

Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) evolution after silicone implants. Who is at risk?

“…DQA1*0102 allele was considerably more common in patients who developed myositis after silicone [52]. More importantly, the co-occurrence of type-1 diabetes and celiac disease [53] in the same patients was linked to HLA-C exemplifying both genetic predisposition as well as coexistence of two immunologic phenomena. Taken together, these associations between HLA subgroups and autoimmunity are believed to represent a hyperactive immune system with the disadvantage of autoimmunity risk in one hand and an evolutionary advantage in fighting infections, such as enteric fever [54].…”

Incidence of Type 1 Diabetes Is Not Increasing in a Population-Based Cohort in Olmsted County, Minnesota, USA

“…Current knowledge suggests that a gluten-free diet may affect dendritic cells and the subsequent development of diabetes (28). HLA markers may help determine the risk of CD in patients with T1D (29, 30). The role of perinatal environment and the microbiome is also under examination.…”

Type 1 Diabetes in the Young: Organization of two National Centers in Israel and Slovenia / Sladkorna Bolezen Tipa 1 Pri Otrocih in Mladostnikih: Organizacija Dela V Dveh Nacionalnih Centrih V Izraelu in Sloveniji

“…Clinical research includes diabetes-prevention trials ( 40 ), introduction of new drugs ( 41 , 42 ) and new technologies ( 43 , 44 ) for the treatment of diabetes, along with psychological investigations ( 45 – 47 ). Additionally, applied basic research conducted in both centres contributes to the knowledge on disease mechanisms ( 48 – 52 ). Both centres also participate in international data collection and benchmarking within the Centre of Reference SWEET project ( 53 ).…”