Association of multispecific red blood cell alloimmunization with HLA-Class II variants is related to Rh phenotypes

Abstract

It remains unclear, why only some patients form alloantibodies against foreign RBC antigens. Transfusion of red blood cell (RBC) products and pregnancy are the most relevant causes of immunization against RBC alloantigens. Here we investigated the relationship between RBC alloantibodies, Rh phenotype, and HLA phenotype among patients with multiple RBC alloantibodies METHODS: In a group of 124 multi-responders-including both pregnant women and transplant recipients-we analysed the distribution of HLA-Class II variants in subgroups of multi-responders to RBC alloantigens according to their Rh status. RESULTS: As expected, the RhD-negative phenotype was overrepresented in our alloimmunized group (49.2 %) compared to in the general population. Importantly, HLA-DRB1*15 carriers were signifi cantly overrepresented among D-negative multi-responders compared to D-positive multi-responders (Pc = 0.045). Furthermore, the linked HLA-DRB1*13, HLA-DQB1*06, and HLA-DQA1*01 variants were more frequent in individuals with the DCCee phenotype than in other RhD-positive phenotypes. CONCLUSION: Our present fi ndings showed that RBC multispecifi c alloimmunization was associated with particular HLA-Class II variants based on Rh status (Tab. 3, Ref. 22).

The influence of HLA allele and haplotype on RhE alloimmunization among pregnant females in the Chinese Han population

“…High-frequency screening rate of anti-E antibodies in pregnant females makes anti-E one of the main influencing factors of HDFN [25,26]. Diversity of HLA class molecules in individuals have been reported to be important factors influencing RBC alloimmunization [12]. Therefore, HLA genotypes were investigated between RhE The association between HLA-DRB1*09:01 and RhE alloimmunization susceptibility has been reported in our previous study [13].…”

“…High‐frequency screening rate of anti‐E antibodies in pregnant females makes anti‐E one of the main influencing factors of HDFN [25, 26]. Diversity of HLA class molecules in individuals have been reported to be important factors influencing RBC alloimmunization [12]. Therefore, HLA genotypes were investigated between RhE responders and non‐responders among Chinese Han pregnant females in this study, with the aim of elucidating relationships between HLA diversity and RhE alloimmunization during pregnancy.…”

“…The classical HLA class I and class II genes (HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ and HLA-DP) are highly polymorphic [9], and different HLA alleles present different alloantigenic peptides, potentially influencing the T-cell immune response [10]. Therefore, HLA gene polymorphism may influence the recipients' immune susceptibility to RBC alloantigens [11][12][13].…”

HLA Class II regulation of immune response in sickle cell disease patients: Susceptibility to red blood cell alloimmunization (systematic review and meta‐analysis)

“…Several studies have associated variants of HLA Class II with RBC alloimmunization and whether the inheritance of HLA Class II phenotypes provides susceptibility or protection against the formation of RBC alloantibodies [ 5 , 7 , 15 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. However, only a handful of these studies focused on the SCD population [ 5 , 7 , 15 , 23 , 24 ].…”

“…Many studies associated RBC alloimmunization with HLA‐DRB1 variants indicating the role of HLA restriction in susceptibility to forming RBC antibodies, particularly in multi‐responders. Maluskova et al demonstrated the association of HLA‐DRB1*15 with multiple antibody responsiveness in relation to Rh phenotypes [ 25 ]. This supported the hypothesis that certain HLA polymorphisms could further increase susceptibility to multi‐responsiveness towards RBC antigens.…”