Recipient factors influencing red blood cell alloimmunization

Abstract

Red blood cell (RBC) alloantibodies develop in a subset of individuals following exposure to non‐self RBCs through transfusion, pregnancy or other activities; these antibodies can lead to difficulty locating compatible RBCs, acute or delayed haemolytic transfusion reactions, or haemolytic disease of the newborn. Alloimmunization is underestimated due in part to antibody evanescence, the random nature of post‐transfusion antibody screens, fragmented medical care and the lack of widespread antibody registries. Factors that influence who will develop detectable alloantibodies are not well understood. Transfusion burden is one risk factor for alloimmunization, though many highly transfused individuals never form alloantibodies despite exposure to many RBC units (and many non‐self blood group antigens). Individuals with sickle‐cell disease (SCD) and myelodysplastic syndrome (MDS) are more likely to form RBC alloantibodies than most other patient populations. Individuals with rheumatologic and other forms of autoimmunity, though not chronically transfused, are also at higher‐than‐average risk of forming RBC alloantibodies. Inflammation, in a broad sense, is one common thread amongst these diagnoses associated with high prevalence rates of RBC alloimmunization. Reductionist murine models support some types of inflammation (including viral‐like stimuli) around the time of RBC exposure as being associated with an increased likelihood of alloantibody formation. Strategies other than transfusion avoidance or extended antigen matching beyond ABO/Rh would be beneficial to prevent new RBC alloantibody formation, especially in patients at highest risk.

Somatic mutations show no clear association with red blood cell or human leukocyte antigen alloimmunization in de novo or therapy‐related myelodysplastic syndrome

“…Thus, we may be underpowered to detect weaker associations. Furthermore, not all of our patients had a history of in‐house transfusion, which may explain why our alloimmunization prevalence of 11.1% is less than prior studies, 11%–58.6% 3–13 . This is a limitation of performing a study in a tertiary care center as many patients are diagnosed or managed at outside centers with records unavailable at the tertiary center.…”

“…Furthermore, not all of our patients had a history of in-house transfusion, which may explain why our alloimmunization prevalence of 11.1% is less than prior studies, 11%-58.6%. [3][4][5][6][7][8][9][10][11][12][13] This is a limitation of performing a study in a tertiary care center as many patients are diagnosed or managed at outside centers with records unavailable at the tertiary center. Many patients had reported outside transfusion data, while others had no outside clinical records available, therefore no further assessment was performed.…”

“…Recent models have demonstrated chronic innate immune signaling may act as a driver for development of MDS and certain mutations cause continual MDS‐associated innate immune system dysregulation 4,17–19 . As chronic inflammatory conditions associate with alloimmunization, it is conceivable that the same inflammatory model described in MDS may also potentiate antibody formation 4,7,20 .…”

“…3,9,[14][15][16] Recent models have demonstrated chronic innate immune signaling may act as a driver for development of MDS and certain mutations cause continual MDSassociated innate immune system dysregulation. 4,[17][18][19] As chronic inflammatory conditions associate with alloimmunization, it is conceivable that the same inflammatory model described in MDS may also potentiate antibody formation. 4,7,20 MDS somatic mutations, some of which are also commonly encountered in clonal hematopoiesis of indeterminate potential (CHIP), have been shown to increase cytokine release and activate inflammatory pathways.…”

“…RBC alloimmunization occurs in approximately 2%-6% of the generalized hospital population, but reported rates in MDS are significantly higher, ranging from 11% to 58.6%. [3][4][5][6][7][8][9][10][11][12][13] Prior work has shown that increased RBC transfusions are associated with increased alloimmunization and likewise that alloimmunization leads to increased transfusion requirements in this group. 3,8 Research in this area using the South Australian-MDS registry has shown low-grade MDS, as defined by the (IPSS-R), is associated with increased risk of alloimmunization, while disease-modifying therapy is associated with decreased risk.…”