Rh alloimmunization remains a challenge for patients with sickle cell disease (SCD) despite transfusion of serologic Rh C, E, and K antigen-matched red cells. Inheritance of altered alleles contributes to the prevalence of Rh antibodies after blood transfusion in patients with SCD and explains approximately one-third of cases. The remainder seem to be stimulated by altered Rh proteins on African American donor red cells. Matching patients with donors on the basis of genotype may mitigate Rh alloimmunization, but the feasibility and resources required are not known. We compared allele frequencies between patients with SCD (n = 857) and African American donors (n = 587) and showed that allele frequencies are similar. Overall, 29% of and 53% of alleles are altered in patients and African American donors. We modeled genotype matching compared with serologic Rh D, C, and E, along with K antigen matching, and found that approximately twice the number of African American donors would be required for genotype vs Rh serologic matching at our institution. We demonstrated that African American donor recruitment is necessary to maintain an adequate supply of C-, E-, and K-negative donor units to avoid depleting the Rh-negative (RhD) blood supply. Our results suggest that prophylactic genetic matching for patients with SCD is feasible with a donor pool comprised primarily of African-Americans and would optimize the use of our existing minority donor inventory. The current cost of genotyping all minority donors and management of the data remain limiting factors.
SUMMARY
Antibodies have been used for over a century in the prevention and treatment of infectious disease. They are used most commonly for the prevention of measles, hepatitis A, hepatitis B, tetanus, varicella, rabies, and vaccinia. Although their use in the treatment of bacterial infection has largely been supplanted by antibiotics, antibodies remain a critical component of the treatment of diptheria, tetanus, and botulism. High-dose intravenous immunoglobulin can be used to treat certain viral infections in immunocompromised patients (e.g., cytomegalovirus, parvovirus B19, and enterovirus infections). Antibodies may also be of value in toxic shock syndrome, Ebola virus, and refractory staphylococcal infections. Palivizumab, the first monoclonal antibody licensed (in 1998) for an infectious disease, can prevent respiratory syncytial virus infection in high-risk infants. The development and use of additional monoclonal antibodies to key epitopes of microbial pathogens may further define protective humoral responses and lead to new approaches for the prevention and treatment of infectious diseases.
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