Background - Hematological disorders are often treated with blood transfusions. Many blood group antigens and variants are population-specific, and for patients with rare blood types, extensive donor screening is required to find suitable matches for transfusion. There is a scarcity of knowledge regarding blood group variants in Aboriginal Australian populations, despite a higher need for transfusion due to the higher prevalence of renal diseases and anemia. Materials and methods - In this study, we applied next-generation sequencing and analysis to 245 samples obtained from Aboriginal Australians from South-East Queensland, to predict antigen phenotypes for 36 blood group systems. Results - We report potential weak antigens in blood group systems RH, FY and JR that have potential clinical implications in transfusion and pregnancy settings. These include partial DIII type 4, weak D type 33, and Del RHD (IVS2-2delA). The rare Rh phenotypes D+ C+ E+ c- e+ and D+ C+ E+ c+ e- were also detected. Discussion - The comprehensive analyses of blood group genetic variant profiles identified in this study will provide insight and an opportunity to improve Aboriginal health by aiding in the identification of appropriate blood products for population-specific transfusion needs.

BACKGROUND:We report an obstetric case involving an RhD-positive woman who had developed a red blood cell (RBC) antibody that was not detected until after delivery of a newborn, who presented with a positive direct antiglobulin test result. Immunohematology studies suggested that the maternal antibody was directed against a low-prevalence antigen on the paternal and newborn RBCs. RESULTS:Comprehensive blood group profiling by targeted exome sequencing revealed a novel nonsynonymous single nucleotide variant (SNV) RHCE c.486C>G (GenBank MZ326705) on the RHCE*Ce allele, for both the father and newborn. A subsequent genomic-based study to profile blood groups in an Indigenous Australian population revealed the same SNV in 2 of 247 individuals. Serology testing showed that the maternal antibody reacted specifically with RBCs from these two individuals. DISCUSSION:The maternal antibody was directed against a novel antigen in the Rh blood group system arising from an RHCE c.486C>G variant on the RHCE*Ce allele linked to RHD*01. The variant predicts a p.Asn162Lys change on the RhCE protein and has been registered as the 56th antigen in the Rh system, ISBT RH 004063. CONCLUSION:This antibody was of clinical significance, resulting in a mild to moderate hemolytic disease of the fetus and newborn (HDFN). In the past, the cause of such HDFN cases may have remained unresolved. Genomic sequencing combined with population studies now assists in resolving such cases. Further population studies have potential to inform the need to design population-specific red cell antibody typing panels for antibody screening in the Australian population.

Red cell (RC) alloantibodies occur on exposure to non-self RC antigens in transfusion and pregnancy (typically IgG and clinically significant) or in association with non-RC immune environmental factors (typically IgM and not clinically significant). In Australia, the risk of RC alloimmunisation in First Nations peoples is unknown. We assessed the epidemiology, specificity, and antecedents of RC alloimmunisation via a data linkage retrospective cohort study of Northern Territory (NT) intensive care unit (ICU) patients (2015–2019). Of 4183 total patients, 50.9% were First Nations. In First Nations versus non-First Nations patients, the period prevalence of alloimmunisation was 10.9% versus 2.3%, with 390 versus 72 prevalent alloantibodies detected in 232 versus 48 alloimmunised patients, of which 135 (34.6%) versus 52 (72.2%) were clinically significant specificities. Baseline and follow-up alloantibody testing were available for 1367 patients, in whom new incident clinically significant alloantibodies developed in 4.5% First Nations versus 1.1% non-First Nations patients. On Cox proportional hazards modelling, adjusted hazard ratios (HR) showed First Nations status (HR 2.67 (95% CI 1.05–6.80), p = 0.04) and cumulative RC unit transfusion exposure (HR 1.03 (95% CI 1.01–1.05), p = 0.01) were independent predictors of clinically significant alloimmunisation. First Nations Australian patients are at increased risk of alloimmunisation due to RC transfusion, underscoring the importance of very judicious use of RC transfusions and shared decision-making with patients. Further studies are recommended to explore the role of other (non-RC) immune host factors, given the relative high prevalence of non-clinically significant IgM alloantibodies within alloimmunised First Nations patients.