Storage differentially impacts alloimmunization to distinct red cell antigens following transfusion in mice

Abstract

Introduction The impact of blood storage on red blood cell (RBC) alloimmunization remains controversial, with some studies suggesting enhancement of RBC‐induced alloantibody production and others failing to observe any impact of storage on alloantibody formation. Since evaluation of storage on RBC alloimmunization in patients has examined antibody formation against a broad range of alloantigens, it remains possible that different clinical outcomes reflect a variable impact of storage on alloimmunization to specific antigens. Methods RBCs expressing two distinct model antigens, HEL‐OVA‐Duffy (HOD) and KEL, separately or together (HOD × KEL), were stored for 0, 8, or 14 days, followed by detection of antigen levels prior to transfusion. Transfused donor RBC survival was assessed within 24 h of transfusion, while IgM and IgG antibody production were assessed 5 and 14 days after transfusion. Results Stored HOD or KEL RBCs retained similar HEL or KEL antigen levels, respectively, as fresh RBCs, but did exhibit enhanced RBC clearance with increased storage age. Storage enhanced IgG antibody formation against HOD, while the oppositive outcome occurred following transfusion of stored KEL RBCs. The distinct impact of storage on HOD or KEL alloimmunization did not appear to reflect intrinsic differences between HOD or KEL RBCs, as transfusion of stored HOD × KEL RBCs resulted in increased IgG anti‐HOD antibody development and reduced IgG anti‐KEL antibody formation. Conclusions These data demonstrate a dichotomous impact of storage on immunization to distinct RBC antigens, offering a possible explanation for inconsistent clinical experience and the need for additional studies on the relationship between RBC storage and alloimmunization.

The Development and Consequences of Red Blood Cell Alloimmunization

“…Similarly, removal of the antiphagocytic marker CD47 from RBCs enhances RBC removal and antibody formation in the absence of any storage, heat, chemical treatment, or passive antibody-mediated removal, suggesting that simply accelerating RBC removal in the absence of RBC damage (heat or chemical treatment) or antibody coating may facilitate alloimmunization ( 99 , 100 ). However, it should be noted that storage does not uniformly result in enhanced alloantibody development; storage decreases antibody formation following KEL RBC transfusion ( 101 ). Intriguingly, simultaneous transfusion of nonstored (fresh) and stored HOD RBCs partially reverses the impact of storage on enhanced alloantibody formation ( 102 ).…”

Plasmodium knowlesi (Pk) Malaria: A Review & Proposal of Therapeutically Rational Exchange (T-REX) of Pk-Resistant Red Blood Cells

“…Of major clinical importance, exposure to RBC alloantigens following pregnancy or transfusion can increase the likelihood of RBC alloimmunization against other alloantigens, which increases the probability of transfusion complications and reduces the availability of compatible RBCs for future transfusion [185][186][187][188][189][190]. As a result, patients who require chronic transfusions often receive RBCs matched for alloantigens beyond ABO and RhD to reduce the likelihood of RBC alloimmunization [191][192][193][194][195]. As patients with sickle cell disease are prone to developing alloantibodies and associated complications following RBC exposure [196][197][198][199][200][201][202], extended phenotype-matching RBC units (i.e., for alloantigens C, E, and K) for RBCX is routinely used when performing these procedures.…”

Galectin-4 Antimicrobial Activity Primarily Occurs Through its C-Terminal Domain

“…Gaps in adaptive immunity toward molecular mimicry are perhaps most apparent toward microbes that express variants of mammalian ABO(H) blood group antigens. In contrast to red blood cell (RBC)-induced alloantibody formation ( 13 , 14 , 15 , 16 , 17 , 18 , 19 ), antibodies against ABO(H) antigens are naturally occurring and form within the first few months of life ( 20 ). While conflicting data exist regarding the development of naturally occurring anti-ABO(H) antibodies ( 21 , 22 , 23 , 24 , 25 ), several studies suggest that microbes that express ABO(H)-like antigens may stimulate anti-ABO(H) antibody formation relevant to transfusion and transplantation ( 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ).…”