Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease

Abstract

Background Alloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization. Study design Two-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT-HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p-value was calculated using multiple logistic regression. Results While only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 (p=0.02), -DQ3 (p=0.02) and -DQ5 (p=0.01) alleles were significantly higher in non-alloimmunized patients, likely behaving as protective alleles. In addition, multiple logistic regression analysis showed both HLA-DQ2/6 (p=0.01) and HLA-DQ5/5 (p=0.03) combinations constitute additional predictor of protective status. Conclusion Our data suggest that particular HLA-DQ alleles influence the clinical course of RBC transfusion in patients with SCD, which could pave the way towards predictive strategies.

HLA polymorphisms and risk of red blood cell alloimmunisation in polytransfused patients with sickle cell anaemia

“…and -DQB1*05, inferring a protector role of the HLA-DQB1*03 allele for African-American SDC patients (Tatari-Calderone et al, 2016). However, no other study has associated red blood cell alloimmunisation to the HLA-A*23 and HLA-C*06 allelic variants, as we observed in this study.…”

“…() studied 159 American polytransfused patients with SCA and observed that HLA‐DRB1*15:03 was associated with the risk of developing alloantibodies ( P = 0·03, OR = 2·02), whereas the HLA‐DRB1*09:01 conferred protection to patients who did not alloimmunise ( P = 0·008, OR = 0·13); however, such an association was not observed in our study. In contrast, another group of researchers found an association between the alloantibody‐negative group and HLA‐DQB1*02 , −DQB1*03 and –DQB1*05 , inferring a protector role of the HLA‐DQB1*03 allele for African‐American SDC patients (Tatari‐Calderone et al, ). However, no other study has associated red blood cell alloimmunisation to the HLA‐A*23 and HLA‐C*06 allelic variants, as we observed in this study.…”

Susceptible and protective HLA‐DR and HLA‐DQ alleles for Fya alloimmunization in the Croatian population

“…A new protective factor for Fy a alloimmunization, the DQB1*02 allele, was found in this study. The protective effect of the DQB1*02 was also shown for the alloimmunization of patients with sickle cell disease …”

A Toll‐like receptor 2 genetic variant modulates occurrence of bacterial infections in patients with sickle cell disease

“…Patients with SCD present a steady-state inflammatory status (Pitanga et al, 2016). Although some studies addressed the role of inflammatory proteins and cells in SCD (Styles et al, 2000;Tamouza et al, 2002;Hoppe et al, 2003;Adekile et al, 2005;Wallace et al, 2009;Wallace & Linden, 2010;Vingert et al, 2015;Godefroy et al, 2016;Pitanga et al, 2016;Tatari-Calderone et al, 2016), few studies have investigated the potential associations between SCD complications and polymorphisms in genes encoding inflammatory proteins (Norris et al, 1996;Neonato et al, 1999;Styles et al, 2000;Tamouza et al, 2002;Hoppe et al, 2003;Adekile et al, 2005;Fertrin & Costa, 2010;Tatari-Calderone et al, 2016;Sippert et al, 2017;David et al, 2018). In this context, Toll-like receptors (TLRs) are a family of transmembrane and intra-cellular proteins expressed on immune cells that sense pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs).…”