After a marked decrease in the incidence of transfusion-transmitted infectious events, acute non-hemolytic transfusion reactions (ANHTRs) have become the major issues (Combs et al., 2002; Klein & Anstee, 2005). ANHTRs range from mild urticaria, febrile reaction to the most life-threatening transfusion-related acute lung injury (TRALI) (Silliman et al., 2003; Bux 2005). Anti-leukocyte antibodies have been implicated as one of the causative agents of TRALI and febrile reaction (Thompson et al., 1971; Popovsky & Moore, 1985; Payne R, 1957; de Rie et al., 1985). Among anti-leukocyte antibodies, antibodies to human leukocyte antigen (HLA) Class I and/or Class II (HLA Abs) are much more frequently detected than anti-granulocyte antibodies (Bux et al., 1992; Kopko et al., 2003; Zupanska et al., 2007). Sensitive solid phase assays (SPAs) using plastic plates [enzyme-linked immunosorbent assay (ELISA)] or microbeads (flow cytometry or Luminex method) are commercially available for HLA Abs (Stroncek et al., 2007). For TRALI, HLA Abs have been intensively analyzed using SPAs, but for febrile reaction, SPAs have not been used except in our previous study (Payne R, 1957; Decary et al., 1984; de Rie et al., 1985; Imoto et al., 2007). TRALI is frequently accompanied by fever. As Davis et al. have recently reported in ‘a Touch of TRALI’, some of the TRALI cases may have been classified into febrile reaction when the pulmonary manifestation was less severe (Davis et al., 2008). SPA-based analysis of HLA Abs not only for TRALI, but also for febrile reaction and allergic reactions may provide useful information for understanding the role of HLA Abs.
Platelet transfusion refractoriness (PTR) is also an important issue in transfusion medicine. HLA-I Abs in patients' sera have been implicated in most of the PTR cases. For pateitns with PTR, screening of donor(s) for HLA-compatible platelet concentrates (HLA-PCs) is necessary as soon as possible.
We in a regional blood service center of the Japanese Red Cross Society (JRCS) have studied ANHTRs (Imoto et al., 2007). Moreover, we have promoted the registration of donors for HLA-PCs. SPA-based analyses gave us high HLA Abs positivity rates, 36% in female patients' sera and 13% in female donors' sera associated with ANHTRs, whereas no significant difference was observed between allergic and febrile reactions (Imoto et al., 2007). The results suggest that most of the HLA Abs were coincidentally detected but not causative. To evaluate the role of detected HLA Abs, their specific reactivity to cognate HLA Ags should be examined. In this study, by utilizing the HLA-typing data of donors for HLA-PCs, we were able to evaluate the specific reactivity of HLA-I Abs detected in 16 serum samples associated with 12 cases of ANHTRs. The specificity of the HLA-I Abs was identified by the Luminex method using recombinant HLA molecules, LABScreen® Single Antigen. The specific reactivity of the HLA-I Abs to the cognate HLA Ags was evaluated by comparing the specificity of the antibodies and the cognate HLA -A and -B loci, as well as by conventional AHG-LCT. We examined only the specific reactivity of HLA-I Abs, because the HLA-typing data of donors were for HLA-PCs; thus, data only for HLA Class I loci were available. We also present a PTR case with several episodes of febrile as well as allergic reactions, for which we were able to sequentially analyze HLA-I Abs.