HLA Class II-DRB,-DQA and-DQB genotypes in peripheral blood shows shifts during the course of sepsis

Abstract

Undeniably, sepsis is still a profoundly damaging and life-threatening condition for many individuals. With multiple changes in sepsis patients it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. The aim of this study was to investigate genetically determined predisposition to developed sepsis by analysis of distribution of human leukocyte antigen (HLA) class II genes. Samples from patients with sepsis were collected at Pauls Stradiņš Clinical University Hospital, Latvia, in an intensive care unit between October 2016 and May 2017. The study group included 62 patients with sepsis, who were genotyped for HLA-DR; DQ using real time polymerase chain reaction-sequence specific primer (RT PCR-SSP). As a control group, data of 100 individuals were taken from the genetic bank of RSU Joint Laboratory of Clinical Immunology and Immunogenetics. The summarised results showed that the frequency of alleles DRB1∗04:01 (OR = 5.54; 95% CI = 1.88-16.29); DRB1∗07:01 (OR = 19.03; 95% CI = 2/37-152.82); DQA1∗05:01 (OR = 14.17; 95% CI = 5.67-35.4); and DQB1∗02:01 (OR = 50.00; 95% CI = 2.90-861.81) were significantly increased in patients with sepsis compared to the control group patients. The frequency of DRB1∗16:01 (OR = 0.17, 95% CI = 0.04-0.59); DRB1∗17:01 (OR = 0.04; 95% CI = 0.00-0.69); DQA1∗01:01 (OR = 0.04; 95% CI = 0.00-0.31); DQA1∗01:02 (OR = 0.03; 95% CI = 0.00-0.23); DQB1∗02:02 (OR = 0.12; 95% CI = 0.03-0.42) alleles was lower in sepsis patients than in control subjects. The most frequent HLA-DRB1/DQA1/DQB1 haplotypes that was significantly increased in patients with sepsis were: DRB1∗01:01/DQA1∗05:01/DQB1∗03:01 (OR = 12.6; 95% CI = 1.51-105.0; p < 0.003). Sepsis patients with pneumonia and alleles and DRB1 04:01; 07:01, DQB1 02:01 had the highest mortality rate. Undoubtedly, our preliminary data showed that development of sepsis can be associated with alleles and haplotypes of HLA class II genes. For more precise conclusion the research should be continued to include a larger patient group.