Shigeharu Uchida

Residual risk of transfusion‐transmitted hepatitis B virus (HBV) infection caused by blood components derived from donors with occult HBV infection in Japan

BACKGROUND: Nucleic acid amplification testing (NAT) for hepatitis B virus (HBV) during blood screening has helped to prevent transfusion‐transmitted HBV infection (TT‐HBV) in Japan. Nevertheless, 4 to 13 TT‐HBV infections arise annually.

Analysis of risk factors for post-transfusion graft-versus-host disease in Japan

Abstract We distributed a questionnaire to highlight the effects of post transfusion graft-versus-host disease (PT-GVHD) and to elucidate the risk factors that would predispose people to the disease. The questionnaire described the pathogenesis and the clinical profiles of PT-GVHD and was distributed to doctors in Japan whose hospital conducted more than 1000 units of blood transfusions a year. Doctors were asked about their awareness and experience of PT-GVHD cases. Those who had seen cases of PT-GVHD were then asked to detail clinical course and laboratory data. Of the 14 083 doctors who replied to the first question, 47·4% did not realise that PT-GVHD could occur in immunocompetent hosts. From 304 cases where detailed information was supplied, 171 were considered clinically compatible with PT-GVHD. From these it seems that the risk factors linked to PT-GVHD are cardiovascular surgery, cancer, fresh and consanguineous blood transfusion, and being male. Patients with any of these factors should have some prophylactic therapy such as irradiation of blood before transfusion.

Cytomegalovirus (CMV) seroprevalence in Japanese blood donors and high detection frequency of CMV DNA in elderly donors

The current prevalence of cytomegalovirus (CMV) in Japan and the risk of CMV transfusion transmission are unknown in the era of seronegative leukoreduced blood components.

Establishment of culture systems for Genotypes 3 and 4 hepatitis E virus (HEV) obtained from human blood and application of HEV inactivation using a pathogen reduction technology system.

It has been demonstrated that the hepatitis E virus (HEV) can be transmitted via blood transfusion, and the risk of HEV transmission via transfusion has become a major global concern. An HEV culture system for blood‐derived HEV has been sought to obtain valuable knowledge of the virus and the risk of HEV infection through blood products.

Estimation of the infectious viral load required for transfusion-transmitted human T-lymphotropic virus type 1 infection (TT-HTLV-1) and of the effectiveness of leukocyte reduction in preventing TT-HTLV-1.

The risk of transfusion‐transmitted human T‐lymphotropic virus type 1 infection (TT‐HTLV‐1) after prestorage leucocyte reduction (LR) remains unknown, as the proviral load in the blood component that would cause TT‐HTLV‐1 is undetermined. On the basis of the distribution of HTLV‐1 proviral load among HTLV‐1‐sero‐positive blood donors, we attempted to estimate the proviral load for transfusion‐related infectivity. We also discuss the effectiveness of LR in preventing TT‐HTLV‐1.

Late Onset Post-Transfusion Hepatitis E Developing during Chemotherapy for Acute Promyelocytic Leukemia

We herein report the case of a leukemia patient who developed hepatitis E seven months after undergoing a transfusion with contaminated blood products. The latency period in this case was significantly longer than that of typical hepatitis E. Recently, chronic infection with hepatitis E virus (HEV) genotype 3 has been reported in immunocompromised patients. There is a possibility that our patient was unable to eliminate the virus due to immunosuppression following chemotherapy and the administration of steroids. The prevalence of HEV in healthy Japanese individuals is relatively high and constitutes a critical source of infection via transfusion. Hepatitis E is an important post-transfusion infection, and immunocompromised patients may exhibit a long latency period before developing the disease.

A Monoclonal Antibody with Broad Reactivity to Human Interferon-α Subtypes Useful for Purification of Leukocyte-Derived Interferon

A monoclonal antibody to human interferon‐α, termed HT‐1 antibody, with a broad reactivity to various subtypes of interferon‐α was prepared. It bound and neutralized all of the four subtypes of E. coli‐derived human recombinant interferon‐α (aL1, aL2, aL4, and aL6) tested; it also neutralized human natural leukocyte interferon but only partially. Human interferon‐β and ‐γ were not bound. The antibody conjugated to Sepharose beads retained over 90% of human leukocyte interferon induced by Sendai virus. The bound interferon was recovered by acid elution in good yields and in almost pure form (specific activity was about 2 ′ 108 international units/mg protein). The purified interferon showed, in SDS‐polyacrylamide gel electrophoresis, an activity profile with major peaks in a mol. wt. range of 17,000–22,000, which completely agreed with the profile shown by polyclonal antibody‐purified interferon. Such purified leukocyte interferon‐α preparations containing most of the naturally occurring subtypes can be useful for clinical and other purposes.

Restricted use of T-cell receptor V beta genes in posttransfusion graft- versus-host disease

BACKGROUND: Posttransfusion graft‐versus‐host disease (PT‐GVHD) is a pathophysiological process of the immune system. Mature donor T cells that have survived the host defense mechanisms recognize recipient allo‐ antigens through antigen‐specific T‐cell receptors and mount an immune attack against certain host antigens. STUDY DESIGN AND METHODS: To characterize the T cells involved in PT‐GVHD, expression of the T‐cell receptor V beta genes in peripheral blood T cells isolated from four PT‐ GVHD patients was analyzed. T‐cell receptor beta chain cDNA derived from mRNA extracted from peripheral blood lymphocytes was amplified by an inverse polymerase chain reaction method, and the cDNA was subsequently cloned and sequenced. RESULTS: The cDNA clones derived from patients with PT‐GVHD showed remarkable differences in the distribution of T‐cell receptor V beta gene use from that in normal controls. Very restricted T‐cell receptor V beta gene repertoires and preferential expression of certain V beta gene segments were revealed in the peripheral blood lymphocytes of each patients. Shared V beta gene use among the patients was not observed, probably because of HLA differences among the patient‐donor combinations. CONCLUSION: This restricted use reflected in vivo expansion of a limited number of engrafted T‐cell clones at the onset of PT‐GVHD and suggested that those oligoclonal donor T cells may be involved in the induction of PT‐ GVHD.

Evidence of involvement of cytotoxic antibodies directed against patient’s HLA class II produced by transfused donor‐derived B cells in post‐transfusion graft‐versus‐host disease

Post‐transfusion graft‐versus‐host disease (PTGVHD) is one of the most severe side‐effects of blood transfusion. To characterize the effector cells causing this disease, we cloned lymphocytes from a PTGVHD patient’s peripheral blood. T‐cell and B‐cell clones were established, the origins of which were proven to be transfused donor lymphocytes. It was found that the B cells produced IgG that mediated complement‐dependent cytotoxicity to the cells bearing the patient’s HLA class II genotype. Our results suggest, for the first time, the involvement of B‐cell‐produced cytotoxic antibodies directed against patient’s HLA class II in the pathogenesis of PTGVHD.

Transfusion-transmitted hepatitis E in a patient with myelodysplastic syndromes

Patients with haematological diseases occasionally exhibit liver dysfunction during treatment. This liver dysfunction can have various causes such as therapy-related drugs and hepatitis B and C infections, although the cause is unclear in some cases. It was recently reported that some patients initially diagnosed with drug-induced liver dysfunction actually had hepatitis E1. Several cases of transfusion-transmitted hepatitis E infections have also been reported1,2. In Japan, screening for hepatitis E does not appear to be performed at the initial examination of patients with acute hepatitis. This might be because hepatitis E is believed to be orally transmitted and to occur mainly in developing countries and rarely in developed countries. However, hepatitis E is a zoonotic infectious disease. Cases of regional endemic hepatitis E virus (HEV) infection have been increasing in Europe, the United States, and Japan1. Although HEV usually causes self-limited acute hepatitis, it sometimes progresses to a chronic infection. Most cases of chronic infection occur in patients undergoing solid organ or haematopoietic stem cell transplantation, in those receiving anti-cancer or immunosuppressant drugs, and in patients with human immunodeficiency virus infection, in whom the condition may progress to liver cirrhosis3. HEV RNA persisted for a long period during treatment in a patient with T-cell lymphoma4. Reactivation of HEV hepatitis was reported after an allogeneic haematopoietic stem cell transplant in a patient with Philadelphia chromosome-positive acute lymphoblastic leukaemia5. On the other hand, a low risk of HEV reactivation after haematopoietic stem cell transplantation was also reported6. More studies on the risk of HEV reactivation are, therefore, required. Here, we report the case of a patient with a myelodysplastic syndrome (MDS) who developed acute hepatitis due to transfusion-transmitted HEV infection. We also review the literature on the topic.