HLA-A*31 as a marker of genetic susceptibility to sepsis

Abstract

ObjectiveThe HLA haplotype has been associated with many autoimmune diseases, but no associations have been described in sepsis. This study aims to investigate the HLA system as a possible marker of genetic sepsis susceptibility.MethodsThis is a prospective cohort study including patients admitted to an intensive care unit and healthy controls from a list of renal transplant donors. Patients with less 18 years of age; pregnant or HIV positive patients; those with metastatic malignancies or receiving chemotherapy; or with advanced liver disease; or with end-of-life conditions were excluded. The DNA was extracted from the whole blood and HLA haplotypes determined using MiliPlex® technology.ResultsFrom October 2010 to October 2012, 1,121 patients were included (1,078 kidney donors, 20 patients admitted with severe sepsis and 23 with septic shock). HLA-A*31 positive subjects had increased risk of developing sepsis (OR 2.36, 95%CI 1.26-5.35). Considering a p value <0.01, no other significant association was identified.ConclusionHLA-A*31 expression is associated to risk of developing sepsis.

Clinical Pharmacogenetics Implementation Consortium Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update

“…Although HLA alleles have been studied in the context of specific responses to HIV and other pathogens, there are currently no specific diseases or conditions that have been strongly linked to HLA‐B*15:02 or HLA‐A*31:01 independent of drug use . However, HLA‐B*15:02 has also been associated with SJS/TEN from phenytoin use, and other HLA‐B alleles have been strongly associated with adverse drug reactions.…”

“…Although HLA alleles have been studied in the context of specific responses to HIV and other pathogens, there are currently no specific diseases or conditions that have been strongly linked to HLA-B*15:02 or HLA-A*31:01 independent of drug use. [3][4][5] However, HLA-B*15:02 has also been associated with SJS/TEN from phenytoin use, and other HLA-B alleles have been strongly associated with adverse drug reactions. For example, HLA-B*57:01 is associated with abacavir-induced hypersensitivity reaction, and HLA-B*58:01 is associated with allopurinol-induced severe cutaneous adverse reactions (including SJS/TEN and DRESS).…”

HLA-A Locus is Associated With Sepsis and Septic Shock After Traumatic Injury

“…[20][21][22] One study evaluating the association between the HLA region and sepsis in a small mixed surgical and medical population identified HLA-A Ã 31 as a risk factor the development of sepsis. 23 However, this allele was too rare to be evaluated in our study.…”

Use of machine learning-based integration to develop a monocyte differentiation-related signature for improving prognosis in patients with sepsis

“…Two studies published in 2022 also examined the relationship and mechanism associated with the expression of HLA family proteins and sepsis (Horn et al 2022 ; Wu et al 2022 ). In general, during sepsis, monocytes in the body of patients differentiate into those with different states along with progress in the condition of the patient, which also plays an important role in the development of sepsis (Boeddha et al 2018 ; Liu et al 2021 ; Silva et al 2013 ). In particular, the ability of antigen presentation is of great significance for the diagnosis, prognosis, and prediction of sepsis in patients (Silva et al 2013 ; Quadrini et al 2021 ; Hahn et al 2017 ; Fernández-Grande et al 2019 ).…”