Association between sHLA-G and HLA-G 14-bp deletion/insertion polymorphism in Crohn’s disease

Abstract

The aim of this study was to evaluate the association between the HLA-G 14-bp deletion/insertion (Del/Ins) polymorphism and soluble (s) HLA-G production in patients with Crohn's disease (CD). We analyzed also the sHLA-G molecules by ELISA and western blot in plasma samples. Among unselected patients, the 14-bp Del/Ins polymorphism was not significantly associated with increased CD risk neither for alleles (P = 0.371) nor for genotypes (P = 0.625). However, a significant association was reported between the 14-bp Del/Ins polymorphism and CD, in particular in young-onset CD patients for alleles [P = 0.020, odds ratio (OR) = 2.438, 95% confidence interval (CI): 1.13-5.25] but not with adult-onset CD patients. A significant association was reported concerning the genotype Ins/Ins for young-onset CD patients (P = 0.029, OR = 3.257, 95% CI: 1.08-9.77). We observed also a significant increase in sHLA-G measured by ELISA in CD patients compared to controls (P = 0.002). The 14-bp Del/Del and 14-bp Del/Ins genotypes are the high HLA-G producers. Among sHLA-G(positive) patients, 43% of subjects present dimers of HLA-G. The presence of dimers seems to be related to the advanced stages of the disease. The 14-bp Del/Ins polymorphism is associated with an increased risk of CD particularly in young-onset CD patients and controls sHLA-G plasma levels. Dimers of sHLA-G are frequent in advanced disease stages. The above findings indicate that the genetic 14-bp Del/Ins polymorphism in exon 8 of the HLA-G gene is associated with the risk of CD and suggest a role for sHLA-G as a prognostic marker for progressive disease.

Genetic association between HLA-G 14-bp polymorphism and diseases: A systematic review and meta-analysis

“…Notwithstanding that, this meta-analysis revealed inconsistencies between some association studies that have already been published. This statement is based on the following results: i) when we observed data from many conditions (Cervical cancer, Hepatocellular carcinoma, Multiple sclerosis, Rheumatoid arthritis, HIV vertical transmission, Human papillomavirus infection, Heart transplantation, Kidney transplantation, Preeclampsia (mothers), Implantation failure, Miscarriage, e.g), we could verify that some studies found the 14-bp insertion associated with susceptibility to disease development [108,112,[117][118][119]138,140], whereas, others revealed the 14-bp deletion as the allele associated with susceptibility [47,53,79,82,91], and sometimes none was associated [48,49,80,98,101,105,147]; ii) when the disorders were grouped according to conditions exhibiting a hypothetical high (1) or low (2) HLA-G expression, no associations between the 14-bp alleles were All possible associations between 14-bp polymorphism and the clinical situations/diseases were measured by calculating a pooled Odds Ratio (OR) and 95% confidence intervals (CI) for fixed and/or random effect models. The p values resulting from the Q test, τ2 values and of the I2 value were used to measure betweenstudies heterogeneity.…”

Recent Advances in Our Understanding of HLA-G Biology: Lessons from a Wide Spectrum of Human Diseases

“…Moreover, they observed higher sHLA-G levels in CD patients than in controls, and they found that patients with 14 bp del/del and 14 bp del/ins genotypes are the high HLA-G producers. Dimers of sHLA-G were found in advanced disease stage, thus suggesting a role for sHLA-G as a prognostic marker for progressive disease in CD patients [ 65 ]. Dimers of sHLA-G have been also analyzed by Fainardi et al in MS.…”

High plasma soluble levels of the immune checkpoint HLA-G molecule among bodybuilders

“…Studies have shown that adipose tissue secretes various inflammation-related cytokines, such as leptin and IL-6, which can induce chronic low-grade inflammation in obese individuals, with a concomitant stimulation of sHLA-G production, which has anti-inflammatory activities [21,22]. This mechanism is possibly due to compensate the chronic pro-inflammatory state of obesity.…”