Kazunori Nakajima

The impact of anti-HLA antibodies on unrelated cord blood transplantations

The majority of cord blood transplantations (CBTs) have human leukocyte antigen (HLA) disparities. We investigated the impact that patients pretransplantation anti-HLA antibodies have on the outcome of CBTs. Testing for anti-HLA antibody and its specificity was performed retrospectively at the Japanese Red Cross Tokyo Blood Center with sensitive solid-phase antibody detection assays. Among 386 CBTs, which were first myeloablative stem cell transplantations for malignancies and used a single unit of cord blood, 89 tested positive. Among the antibody-positive group, the cord blood did not have the corresponding HLA type for the antibody in 69 cases (ab-positive), while 20 cases had specificity against the cord blood HLA (positive-vs-CB). Cumulative incidence of neutrophil recovery 60 days after transplantation was 83% (95% confidence interval [CI], 79%-87%) for the antibody-negative group (ab-negative), 73% (95% CI, 61%-82%) for ab-positive, but only 32% (95% CI, 13%-53%) for the positive-vs-CB (P < .0001, Gray test). With multivariate analysis, the ab-positive showed significantly lower neutrophil recovery than the ab-negative (relative risk [RR] = 0.69, 95% CI, 0.49-0.96, p = .027). The positive-vs-CB had significantly lower neutrophil recovery (RR = 0.23, 95% CI, 0.09-0.56, P = .001) and platelet recovery (RR = 0.31, 95% CI, 0.12-0.81, P = .017) than the ab-negative. Patients pretransplantation anti-HLA antibodies should be tested and considered in the selection of cord blood.

Activation of the contact system by filtration of platelet concentrates with a negatively charged white cell‐removal filter and measurement of venous blood bradykinin level in patients who received filtered platelets

BACKGROUND: Several recent reports have described hypotensive transfusion reactions in patients receiving platelet concentrates (PCs) filtered through white cell‐reduction filters. It is well known that a negatively charged surface activates the contact system, consisting of factor XII, prekallikrein, and high‐molecular‐weight kininogen.

Anaphylactic transfusion reactions in haptoglobin-deficient patients with IgE and IgG haptoglobin antibodies

BACKGROUND : Patients with haptoglobin deficiency associated with haptoglobin IgG antibodies, who experienced severe nonhemolytic transfusion reactions (NHTRs), have been identified in Japan. Haptoglobin deficiency therefore might be a risk factor for NHTRs.

Seroprevalence of human herpesvirus 8 in human immunodeficiency virus 1- positive and human immunodeficiency virus 1-negative populations in Japan

To determine the seroprevalence of human herpesvirus 8 (HHV8) among human immunodeficiency virus 1 (HIV‐1)‐positive (HIV‐1+) and HIV‐1‐negative (HIV‐1−) populations in Japan, 276 HIV‐1+ patients and 1,000 HIV‐1− blood donors were enrolled in this study. Antibodies against HHV8 latency‐associated nuclear antigen (LANA) were examined through indirect immunofluorescent assay by using a B‐cell line that was infected latently with HHV8 (body cavity‐based lymphoma 1). An HHV8− and Epstein‐Barr virus‐negative B‐cell line (Ramos) was used as a control. Thirty‐two seropositive cases against LANA (anti‐LANA+) were identified among the 276 HIV‐1+ patients who were studied. Five cases were foreigners living in Japan. The risk factor of all 27 Japanese cases was unprotected sexual intercourse, and the great majority of these cases (23 in 27; 85%) reported homosexual/bisexual behavior. Anti‐LANA+ status correlated with the presence of sexually transmitted diseases, such as amoeba and HBV infection, further suggesting male homosexual behavior as the main route of HHV8 transmission in Japan. Only two LANA+ cases were identified among 1,000 HIV− blood donors in Japan; thus, seroprevalence of HHV8 identified by LANA was estimated to be 0.2% among HIV‐1− populations in this country. J. Med. Virol. 57:159–162, 1999.

Role of anti‐human leucocyte antigen class II alloantibody and monocytes in development of transfusion‐related acute lung injury

summary Recently, evidence implicating the roles of the anti‐human leucocyte antigen (HLA) class II antibody in the development of transfusion‐related acute lung injury (TRALI), which is one of the most serious possible side effects of transfusion, has been accumulating. The aim of this study is to clarify the roles of the anti‐HLA DR alloantibody in TRALI development. Cultured human lung microvascular endothelial (LME) cells were incubated with either HLA‐DR15‐positive or HLA‐DR15‐negative monocytes together with serum from a single multiparous donor previously implicated in a clinical case of TRALI and known to contain anti‐HLA DR15 antibody. Production of soluble leukotriene B4 (LTB4) was measured in the supernatant and found to be markedly increased in the presence of HLA‐DR15‐positive monocytes but not with the HLA‐DR15‐negative monocytes or in the absence of LME cells. The vascular cell adhesion molecule‐1 expression in LME cells and leucocyte‐function‐associated molecule‐1 (LFA‐1) expression in HLA‐DR15‐positive monocytes were notably enhanced after combined culture of LME cells, HLA‐DR15‐positive monocytes and TRALI‐inducing anti‐HLA DR15 antibody‐positive serum. In conclusion, anti‐HLA DR alloantibodies may be implicated in LME dysfunction that leads to TRALI, in a monocyte‐dependent manner.

Topical thrombin-induced IgE-mediated anaphylaxis: RAST analysis and skin test studies☆

Bovine topical thrombin (BTT) is a heterologous plasma thrombin concentrate that has been frequently used for the hemostasis since the 1940s. Recently, three patients in Japan went into shock after the topical application of BTT at lesion sites, and two of these patients had received BTT repeatedly. The clinical symptoms and the increased anti-BTT percent RAST counts suggest that these reactions were shock mediated by anti-BTT IgE antibodies. The RAST-inhibition analysis suggested that the antigenic substance(s) were bovine-specific moiety(ies) mainly involved in the contaminant rather than bovine thrombin itself. The skin tests were studied to predict such allergic reactions. The intracutaneous test provoked nonspecific reactions even at the low concentrations of BTT. The prospective study on the predictive value of the prick test with 1000 U/ml (1 mg/ml) of BTT in 192 patients suggested that it is useful to detect highly sensitive patients. In addition, the increased levels of anti-BTT IgE antibodies in patients 1 month after the single administration of BTT suggested the immunogenicity of the topical application of BTT.

Impact of fresh-frozen plasma from male-only donors versus mixed-sex donors on postoperative respiratory function in surgical patients: a prospective case-controlled study

BACKGROUND: To reduce the risk of transfusion‐related acute lung injury (TRALI), plasma products are mainly made from male donors in some countries because of the lower possibility of alloimmunization; other countries are considering this policy. The advantage of male‐only fresh‐frozen plasma (FFP) should be examined in a prospective case‐control study.

Significant Association of KIR2DL3-HLA-C1 Combination with Cerebral Malaria and Implications for Co-evolution of KIR and HLA

Cerebral malaria is a major, life-threatening complication of Plasmodium falciparum malaria, and has very high mortality rate. In murine malaria models, natural killer (NK) cell responses have been shown to play a crucial role in the pathogenesis of cerebral malaria. To investigate the role of NK cells in the developmental process of human cerebral malaria, we conducted a case-control study examining genotypes for killer immunoglobulin-like receptors (KIR) and their human leukocyte antigen (HLA) class I ligands in 477 malaria patients. We found that the combination of KIR2DL3 and its cognate HLA-C1 ligand was significantly associated with the development of cerebral malaria when compared with non-cerebral malaria (odds ratio 3.14, 95% confidence interval 1.52–6.48, Pu200a=u200a0.00079, corrected Pu200a=u200a0.02). In contrast, no other KIR-HLA pairs showed a significant association with cerebral malaria, suggesting that the NK cell repertoire shaped by the KIR2DL3-HLA-C1 interaction shows certain functional responses that facilitate development of cerebral malaria. Furthermore, the frequency of the KIR2DL3-HLA-C1 combination was found to be significantly lower in malaria high-endemic populations. These results suggest that natural selection has reduced the frequency of the KIR2DL3-HLA-C1 combination in malaria high-endemic populations because of the propensity of interaction between KIR2DL3 and C1 to favor development of cerebral malaria. Our findings provide one possible explanation for KIR-HLA co-evolution driven by a microbial pathogen, and its effect on the global distribution of malaria, KIR and HLA.

Risk factor analysis of vasovagal reaction from blood donation

BACKGROUNDnVasovagal reaction (VVR) is the most frequent side effect at blood collection sites.nnnAIMSnTo protect donors, factors contributing to VVR were analysed.nnnMATERIALS AND METHODSnComplications following whole blood and apheresis donations have been recorded and accumulated by the Japanese Red Cross Tokyo Blood Centre. A dataset of 43,948 donors who had no complications was prepared as a control by randomly selecting days in each season in the 2006 and 2007 fiscal years. Factors contributing to 4924 VVR incidents in the 2006 and 2007 fiscal years were analysed by univariate and multivariate logistic regression.nnnRESULTSnThe age, weight, body mass index (BMI), predonation systolic and diastolic pressure, and circulating blood volume were lower, and the pulse was higher, for the VVR group compared to the control group (p<0.0001). The VVR group had more female donors, less sleep, and more time since a meal than the control. In multivariate analysis, significant risk factors for 400 ml whole blood donors, which are the majority of donors, were an age <50 years, being female, a BMI <25, pulse ≥90/min, sleep duration <8 h, the time after eating ≥4 h, a first time donation and circulating blood volume of <4.3 l. Sleep duration of <6 h was shown to be a VVR risk as much as a first time donation.nnnCONCLUSIONnFrom our analysis, the amount of sleep obtained the previous night should be considered at the reception of donors.

Application of bead array technology to simultaneous detection of human leucocyte antigen and human platelet antigen antibodies

Backgroundu2003 Detection of antibodies against human leucocyte antigens (HLA) and human platelet antigens (HPA) is crucial for patients refractory to platelet transfusion therapy. However, a reliable and high‐throughput method for HLA cross‐matching and detecting HPA antibodies has not yet been described.