Acute non-hemolytic transfusion reactions and HLA class I antibody: advantages of solid phase assay compared with conventional complement-dependent assay

Abstract

To evaluate the specific reactivity of HLA Class I antibodies (HLA-I Abs) in acute non-hemolytic transfusion reactions (ANHTRs) using solid phase assays (SPAs) and conventional complement-dependent lymphocyte cytotoxicity test (LCT). ANHTRs are major issues in transfusion medicine. Anti-leukocyte antibodies have been implicated as one of the causative agents of transfusion-related acute lung injury (TRALI) and febrile reaction. Antibodies to HLA Class I and/or Class II (HLA Abs) have been intensively studied using SPAs for TRALI, but not for febrile reaction. About 107 patients and 186 donors associated with ANHTRs were screened for HLA Abs by SPAs such as enzyme-linked immunosorbent assay (ELISA) and the Luminex method. When HLA-I Ab was detected, its specific reactivity was evaluated by comparing its specificity identified by the Luminex method using recombinant HLA molecules and cognate HLA antigens (Ags), as well as LCT with or without anti-human globulin (AHG). The incidences of HLA Abs were as high as 32·7% of patients' serum samples and 16% of donors' serum samples. The incidence of HLA-I Abs did not differ significantly between cases of febrile and allergic reactions. However, HLA-I Abs associated with febrile reaction showed a significantly higher rate of possessing specific reactivity to cognate HLA Ags than those associated with allergic reactions. In addition, the Luminex method enabled the detection of HLA-I Abs much earlier than AHG-LCT in serum samples from a patient with febrile reaction and platelet transfusion refractoriness (PTR). SPAs seem more useful than AHG-LCT for evaluating reactivity of antibodies in ANHTR cases.

Luminex® and Its Applications for Solid Organ Transplantation, Hematopoietic Stem Cell Transplantation, and Transfusion^*

“…Some HNA antibodies can be detected by a separate Luminex LABScreen™ approach. Since the implementation of the Luminex platform for detection of HLAab and HNA antibodies (HNAab), there are numerous reports providing a body of evidence that this higher sensitivity allows the better verification of suspected cases of TRALI [60,61,62]. TRALI is an underreported rare event but the leading cause of transfusion-related morbidity and mortality [63].…”

Adhesive interaction between peripheral blood mononuclear cells and activated platelets in the presence of anti‐human leukocyte antigen Class I alloantibody causes production of IL‐1β and IL‐8

“…Introduction of prestorage leucoreduction has been reported to significantly reduce the incidence of FNHTRs in PCs as well as red blood cells [9–11]. Nevertheless, FNHTRs have still been observed in PCs [9–12]; therefore, another mechanism is operating in the incidence of FNHTRs. In this regard, our current observation may explain an additional mechanism that leads to febrile reactions, when a patient with HLA Class I alloantibody receives a transfusion of PCs.…”

“…In the analysis of acute NHTR, such as febrile and allergic reactions, and transfusion‐related acute lung injury, the incidences of HLA antibodies in patient blood samples were shown to be twofold higher than those in donor blood samples [12]. Interestingly, the rate of possessing specific reactivity to cognate HLA antigens was significantly higher in HLA Class I antibodies associated with febrile reactions than in those associated with allergic reactions [12]. This higher rate of a cognate antigen–antibody relationship in febrile reactions supports our proposal.…”

“…To prevent residual leucocyte‐related transfusion reactions, including febrile reactions, prestorage leucoreduction has been introduced into the blood programme. Prestorage filtration of platelet concentrates (PCs) has been reported to significantly reduce FNHTRs to PCs as well as red blood cells [9–11]; however, FNHTRs have still been observed in the transfusion of even prestorage leucoreduced PCs [9–12].…”

Approach of using established and new laboratory tests to more comprehensively investigate noninfectious and nonhemolytic transfusion reactions – along with the experience in Japan

“…Recently, Imoto et al . clearly showed an association between febrile reactions with, at least, HLA class I antibodies in the plasma of patients. They also confirmed the specific reactivity of the HLA antibodies to cognate HLA antigens at the level of donor–patient pairs.…”