RH genotypes and red cell alloimmunization rates in chronically transfused patients with sickle cell disease: A multisite study in the USA

Narek Israelyan; Sunitha Vege; David F. Friedman; Zhe Zhang; Stacey Uter; Ross M. Fasano; Marianne E.M. Yee; Connie Piccone; Shannon Kelly; Jane S. Hankins; Yan Zheng; Connie M. Westhoff; Stella T. Chou

doi:10.1111/trf.17740

journal article Jan 30, 2024

RH genotypes and red cell alloimmunization rates in chronically transfused patients with sickle cell disease: A multisite study in the USA

Narek Israelyan

Sunitha Vege

David F. Friedman

Zhe Zhang

Stacey Uter Ross M. Fasano Marianne E.M. Yee Connie Piccone Shannon Kelly Jane S. Hankins

Yan Zheng

Connie M. Westhoff

Stella T. Chou

Transfusion Vol. 64 No. 3 pp. 526-535 · Wiley

View at Publisher Save 10.1111/trf.17740

Abstract

AbstractBackgroundRed cell alloimmunization remains a challenge for individuals with sickle cell disease (SCD) and contributes to increased risk of hemolytic transfusion reactions and associated comorbidities. Despite prophylactic serological matching for ABO, Rh, and K, red cell alloimmunization persists, in part, due to a high frequency of variant RH alleles in patients with SCD and Black blood donors.Study Design and MethodsWe compared RH genotypes and rates of alloimmunization in 342 pediatric and young adult patients with SCD on chronic transfusion therapy exposed to >90,000 red cell units at five sites across the USA. Genotyping was performed with RHD and RHCE BeadChip arrays and targeted assays.ResultsPrevalence of overall and Rh‐specific alloimmunization varied among institutions, ranging from 5% to 41% (p = .0035) and 5%–33% (p = .0002), respectively. RH genotyping demonstrated that 33% RHD and 57% RHCE alleles were variant in this cohort. Patients with RHCE alleles encoding partial e antigens had higher rates of anti‐e identified than those encoding at least one conventional e antigen (p = .0007). There was no difference in anti‐D, anti‐C, or anti‐E formation among patients with predicted partial or altered antigen expression compared to those with conventional antigens, suggesting that variant Rh on donor cells may also stimulate alloimmunization to these antigens.DiscussionThese results highlight variability in alloimmunization rates and suggest that a molecular approach to Rh antigen matching may be necessary for optimal prevention of alloimmunization given the high prevalence of variant RH alleles among both patients and Black donors.

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Details

Published: Jan 30, 2024
Vol/Issue: 64(3)
Pages: 526-535
License: View

Authors

N

Narek Israelyan

Department of Pathology and Laboratory Medicine Hospital of the University of Pennsylvania Philadelphia Pennsylvania USA

S

Sunitha Vege

Immunohematology and Genomics Laboratory New York Blood Center Enterprise Long Island City New York USA

D

David F. Friedman

Division of Hematology, Department of Pediatrics The Children's Hospital of Philadelphia Philadelphia Pennsylvania USA; Division of Transfusion Medicine, Department of Pathology and Laboratory Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA

Z

Zhe Zhang

Department of Biomedical Informatics Children's Hospital of Philadelphia Philadelphia Pennsylvania USA

S

Stacey Uter

Division of Hematology, Department of Pediatrics The Children's Hospital of Philadelphia Philadelphia Pennsylvania USA

R

Ross M. Fasano

Center for Transfusion Medicine and Cellular Therapies, Department of Pathology and Laboratory Medicine Emory University School of Medicine Atlanta Georgia USA; Aflac Cancer and Blood Disorders Center Children's Healthcare of Atlanta Atlanta Georgia USA

M

Marianne E.M. Yee

Aflac Cancer and Blood Disorders Center Children's Healthcare of Atlanta Atlanta Georgia USA; Department of Pediatrics Emory University School of Medicine Atlanta Georgia USA

C

Connie Piccone

Pediatric Hematology Carle Foundation Hospital, Carle Illinois College of Medicine Urbana Illinois USA

S

Shannon Kelly

Department of Pediatric Hematology and Oncology UCSF Benioff Children's Hospital Oakland Oakland California USA

J

Jane S. Hankins

Department of Global Pediatric Medicine and Hematology St. Jude Children's Research Hospital Memphis Tennessee USA

Y

Yan Zheng

Department of Pathology St. Jude Children's Research Hospital Memphis Tennessee USA

C

Connie M. Westhoff

Immunohematology and Genomics Laboratory New York Blood Center Enterprise Long Island City New York USA

S

Stella T. Chou

Division of Hematology, Department of Pediatrics The Children's Hospital of Philadelphia Philadelphia Pennsylvania USA; Division of Transfusion Medicine, Department of Pathology and Laboratory Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA

Funding

National Heart, Lung, and Blood Institute Award: R01 HL147879

Doris Duke Charitable Foundation

Cite This Article

Narek Israelyan, Sunitha Vege, David F. Friedman, et al. (2024). RH genotypes and red cell alloimmunization rates in chronically transfused patients with sickle cell disease: A multisite study in the USA. Transfusion, 64(3), 526-535. https://doi.org/10.1111/trf.17740

RH genotypes and red cell alloimmunization rates in chronically transfused patients with sickle cell disease: A multisite study in the USA

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