Aloimunização eritrocitária na doença falciforme: um desafio transfusional no Nordeste do Brasil

Abstract

Introdution: Red cell alloimmunization is a frequent immunological complication of transfusion therapy in individuals with sickle cell disease (SCD), determined by antigenic disparities between donors and recipients, allelic heterogeneity of the RH system, chronic inflammation in SCD and polymorphism of human leukocyte antigens (HLA). Objective: To analyze the erythrocyte phenotypic profile and occurrence of alloantibodies in SCD patients, correlating these with transfusional exposure and the immunogenicity of the main erythrocyte antigens. Methods: Observational, exploratory, analytical and cross-sectional study (2010- 2024) of adult SCD patients (n = 267), both alloimmunized and non-alloimmunized (ABS+ and ABS−), and the antigenic profile of blood donors (n = 1.145) in the State of Sergipe, Brazil. Variables analyzed included age, sex, number of transfusions, ABO, RH, KEL, MNS, FY, JK, P1PK, LE, LU phenotypes, and alloantibody specificities. Ethno-phenotypic analysis through antigenic exposure and alloimmunization risks was estimated by comparing recipient phenotypes with donor antigenic frequencies. Data were structured in spreadsheets, imported to R software (v.4.5.0) with readxl, and analyzed using table1, ggplot2, dplyr, and igraph packages. Alloantibody co-occurrence was represented in modular networks. Results: Alloimmunization was identified in 24.81% of patients, with anti-RH3 and anti-KEL1 being themostprevalentalloantibodies.Co-occurrenceanalysisindicatedassociationsbetweenanti- KEL1, anti-RH3, and anti-MNS3. The ABS+ group received, on average, 13 transfusions versus 5 in the ABS− group (p < 0.001). RH phenotypes such as R1/Ro, Ro/r’, and Ro/Ro, common amongst individuals of African ancestry, showed a greater association with alloimmunization. JK1, RH2, MNS3, FY1, and RH3 antigens showed high immunogenicity. Discussion: Alloimmunization in sickle cell disease (SCD) is strongly associated with recurrent exposuretoincompatibleerythrocyte antigens, evidencedbythe higher frequencyof alloantibodies in multiply transfused patients. The higher prevalence of anti-RH3, anti-KEL1, and anti-MNS3 alloantibodies reinforces the relevance of the RH, KEL, and MNS systems. The predominance of R1/Ro, Ro/r’ and Ro/Ro phenotypes among alloimmunized patients highlights the role of African ancestry and their antigenic and genetic diversity in relation to donors. Such incompatibilities increase immunological risk and emphasize the need for transfusional strategies and public policies that prioritize the interoperabilitywith adjustments for digital data management aimed at integrating information and transfusion studies between the blood network and other health institutions, as well as the implementation of molecular techniques and ethnic-phenotypic donor banks to minimize transfusion exposure.Conclusion: The high frequency and co-occurrence of alloantibodies observed reflect thehighexposureandphenotypic incompatibilitiesbetweenblooddonorsandpatientswithsickle cell disease, confirming that intensitytransfusion is an important risk factor (p< 0.001). When estimating the immunogenic potential, where JK1>RH2>MNS3>FY1>RH3, the need arises for strategies with similar and compatible phenotypes, such as those from black donors (both black and brown).