The lysophospholipid‐binding molecule CD1D is not required for the alloimmunization response to fresh or stored RBCs in mice despite RBC storage driving alterations in lysophospholipids

• DOI: 10.1111/trf.16554
• Publication Date: 2021-06-28T16:36:14Z
• Authors: Jelena Medved; Brittney M. Knott; Soraya N. Tarrah; Andria N. Li; Neha Shah; Tamara C. Moscovich; Alexis R. Boscia; Juan E. Salazar; Manjula Santhanak...; Jeanne E. Hendric...; Xiaoyun Fu; James C. Zimring; Chance John Luckey
• Keywords: Male; Mice, Knockout; 0301 basic medicine; Isoantigens; Erythrocytes; Mice, Inbred Strains; Mass Spectrometry; 3. Good health; Mice; 03 medical and health sciences; 0302 clinical medicine; Immunoglobulin M; Antibody Specificity; Blood Preservation; Isoantibodies; Immunoglobulin G; Alarmins; Animals; Blood Transfusion; Female; Immunization; Antigens, CD1d; Lysophospholipids; Duffy Blood-Group System

AbstractBackgroundDespite the significant adverse clinical consequences of RBC alloimmunization, our understanding of the signals that induce immune responses to transfused RBCs remains incomplete. Though RBC storage has been shown to enhance alloimmunization in the hen egg lysozyme, ovalbumin, and human Duffy (HOD) RBC alloantigen mouse model, the molecular signals leading to immune activation in this system remain unclear. Given that the nonclassical major histocompatibility complex (MHC) Class I molecule CD1D can bind to multiple different lysophospholipids and direct immune activation, we hypothesized that storage of RBCs increases lysophospholipids known to bind CD1D, and further that recipient CD1D recognition of these altered lipids mediates storage‐induced alloimmunization responses.Study Design and MethodsWe used a mass spectrometry‐based approach to analyze the changes in lysophospholipids that are induced during storage of mouse RBCs. CD1D knockout (CD1D‐KO) and wild‐type (WT) control mice were transfused with stored HOD RBCs to measure the impact of CD1D deficiency on RBC alloimmunization.ResultsRBC storage results in alterations in multiple lysophospholipid species known to bind to CD1D and activate the immune system. Prior to transfusion, CD1D‐deficient mice had lower baseline levels of polyclonal immunoglobulin (IgG) relative to WT mice. In response to stored RBC transfusion, CD1D‐deficient mice generated similar levels of anti‐HOD IgM and anti‐HOD IgG.ConclusionAlthough storage of RBCs leads to alteration of several lysophospholipids known to be capable of binding CD1D, storage‐induced RBC alloimmunization responses are not impacted by recipient CD1D deficiency.