Even though described studies use an RBC transfusion magic size, the principle demonstrated could extend to platelet and HLA antigens, with potential relevancy to both solid organ and bone marrow transplantation
Even though described studies use an RBC transfusion magic size, the principle demonstrated could extend to platelet and HLA antigens, with potential relevancy to both solid organ and bone marrow transplantation. RBCs expressing a B-cell epitope (hen egg lysozyme [HEL]) fused to (OVA)323-339. Whereas illness only induced no detectable anti-HEL, subsequent RBC transfusion induced 100- to 1000-collapse more anti-HEL in mice that had been previously infected compared with control mice. This effect did not happen with wild-type polyoma disease or RBCs expressing HEL Voruciclib only. Collectively, these data indicate that prior exposure to a pathogen with small peptide homology to RBC antigens can lead to an enhanced main alloantibody response. As such priming is not detectable by current clinical tests, it is unfamiliar to what degree this happens in human being Voruciclib alloimmunization. Intro Humoral immunization to reddish blood cell (RBC) alloantigens can occur as a result of transfusion or pregnancy. Antibodies against clinically significant blood group alloantigens (ie, RhD, Kell, Kidd, etc) can lead to both hemolysis of transfused RBCs and/or to hemolytic disease of the newborn.1,2 However, unlike humoral immunization to microbial illness, which methods 100% in immunocompetent individuals, exposure to RBC alloantigens induces a measurable antibody response in only a subset of recipients. Alloimmunization to the RhD antigen on RBCs ranges from 20% to 80%, with only 3% to 10% of recipients becoming immunized to the remaining RBC antigens (eg, Kell, Duffy, Kidd), despite chronic transfusion.3C5 The reason why some transfused patients but not others become alloimmunized is unclear, and factors influencing alloimmunization have been only partially defined. Immunogenetics takes on some part in variability of alloimmunization to blood products, as antibody reactions Voruciclib to particular alloantigens are limited to distinct recipient human being leukocyte antigen (HLA) types.6C8 In addition, genetic variants outside of HLA may regulate RBC alloimmunization. 9 Environmental variations between recipients also likely impact alloimmunization, as genetically identical animals still have variable alloantibody reactions to transfused RBCs.10,11 One such environmental variable may be the inflammatory status of the recipient, which has been shown to have a considerable effect upon alloimmunization to transfused RBCs in mice,10,12,13 and potentially in human beings.14 In the current report, we hypothesize that an additional potential element is small peptide homology between microbial-derived peptides and blood group antigens. It has long been appreciated that alloimmunity can be induced through exposure to microbial antigens that mimic the 3-dimensional structure and epitopes of alloantigens (molecular mimicry); therefore, antibodies generated against the microbial antigen can cross-react with alloantigens. This is a well-documented event with anti-ABO antibodies, where humans make antibodies against nonCself- ABO antigens without any prior exposure through transfusion, because of immunization with gut microbes that express A and/or B antigens.15 In the context of immunoglobulin G (IgG) responses to protein alloantigens, limited cross-reactivity of anti-RBC antibodies and microbes has been observed for K and Jkb antigens.16,17 However, the possibility of significant molecular mimicry inducing antibodies to non-ABO RBC antigens has been largely rejected, because alloantibodies against Voruciclib additional alloantigens (eg, RhD, RhCc, RhEe, Kell, Duffy, Kidd) are rarely if ever detected in the absence of prior exposure to alloantigen through transfusion or pregnancy.2,18 A second potential mechanism of molecular mimicry, which has not been thoroughly evaluated in the context of humoral alloimmunization, is Voruciclib similarity at the level of CD4+ T-cell epitopes in the absence of mimicry of the 3-dimensional blood group antigen identified by antibodies. In this case, mimicry would be restricted to homology of short peptide sequences offered by major histocompatibility complex class II (MHC II). Herein, we statement a series of microbial peptides with considerable similarity or identity to peptides comprising the polymorphisms responsible for 3 pairs of clinically significant antithetical human being RBC alloantigens (K/k, Fya/Fyb, and PRKM8IP Jka/Jkb). Based on these findings, we hypothesize that CD4+ T-cell reactions to some microbes cross-react with CD4+ T-cell epitopes of RBC alloantigens. Alloantibody binding to blood group alloantigens typically requires exact 3-dimensional structure of the antigen. Because the.