Michi Hisano

Inhibitory effect of catechin against the superantigen staphylococcal enterotoxin B (SEB)

Staphylococcal superantigens (SsAgs) have gained attention as one of the factors aggravating atopic dermatitis (AD) and several potential mechanisms of AD aggravation by SsAgs have been reported. Tea catechin has been found to have many unique antimicrobiological activities such as antibacterial, antiviral, antifungal and antitoxic effects. In the present study, we investigated the inhibitory effect of the green tea catechin extract, Polyphenon, and (−)-epigallocatechin gallate (EGCg) on staphylococcal enterotoxin B (SEB) and its mechanisms of action, and we also discuss the possibility of therapeutic benefits for AD patients of tea catechin. Polyphenon inhibited the lethal toxicity of SEB and the SEB-induced production of TNF-α, IFN-γ and IL-4 following its intraperitoneal administration to BALB/c mice. Although Polyphenon is composed of several isomers among which EGCg is approximately 50% of the total, we considered that most of the inhibitory effect of Polyphenon in mice could be attributed to EGCg. EGCg was immediately bound to SEB molecules and neutralized SEB in a dose- and incubation time-dependent manner without molecular weight alteration of the SEB molecule. Furthermore, EGCg inhibited SEB-induced TNF-α and IFN- γ production and IL-2, IFN- γ, IL-10 and IL-12 p40 mRNA expression in human PBMCs from normal donors in a dose-dependent manner. Inhibition of SsAg-induced T-cell activation by catechin was observed in both in vivo and in vitro studies, suggesting that catechin may be useful in the treatment of AD.

Relationship of Th1/Th2 cell balance with the immune response to influenza vaccine during pregnancy

To determine the optimal timing for influenza vaccination in pregnant women, we measured alterations in the types 1 and 2 T helper cell (Th1/Th2) balance during pregnancy, monitored specific immunity to inoculated antigens after vaccination with inactivated influenza vaccine, evaluated the relevance of the Th1/Th2 ratio and immune responses to the vaccination, monitored the maintenance of high antibody titers until delivery and measured the transplacental antibody transfer rate. No significant alterations of the Th1/Th2 balance were noted in the 65% of pregnant women among whom the Th1/Th2 ratio was lower than 9.9% in the first trimester. In those groups with a ratio higher than 10% in the first trimester, there was a tendency for the ratio to decrease as gestation advanced. The efficiency of immunization was not influenced by the Th1/Th2 status or by the stage of gestation. The antibody titer decreased steadily with time from 1 month after vaccination to the time of delivery. Conversely, the transfer rate of antibodies from maternal to fetal blood at the time of delivery increased with the duration of gestation after vaccination. Nevertheless, the antibody titers in both maternal and fetal blood were sufficient to afford protection against infection. Thus, efficient influenza vaccination can be undertaken at any stage of pregnancy. J. Med. Virol. 81:1923–1928, 2009.

Tyrosine phosphorylation of the linker for activator of T cells in mast cells by stimulation with the high affinity IgE receptor.

Aggregation of the high affinity IgE receptors (FcepsilonRI) on basophils and mast cells, members of the immune receptor family, initiates a cascade of events that results in the release of inflammatory mediators. This pathway involves the activation of several protein-tyrosine kinases, including Lyn, Syk, Btk, and Fak that induce the tyrosine phosphorylation of various proteins. The linker for activation of T cells (LAT), was originally found as a ZAP-70 tyrosine kinase substrate that linked T cell receptors to cellular activation, and was expressed in T cells, NK cells and mast cells. Here we show that LAT expressed in the RBL-2H3 rat mast cell line is tyrosine-phosphorylated after aggregation of FcepsilonRI. The tyrosine phosphorylation of the LAT was dramatically enhanced after receptor aggregation. Furthermore, a tyrosine-phosphorylated 80-kDa protein associated with LAT transiently after receptor aggregation. GST fusion proteins containing parts of PLCgamma or PI3 kinase can bind LAT. These results suggest that LAT plays an important role not only in T cell, but also in mast cell activation, and that the association among these signaling molecules is critical for FcepsilonRI-mediated intracellular signal transduction in mast cells.

Herpes simplex virus 2-associated hemophagocytic lymphohistiocytosis in a pregnant patient.

BACKGROUND: Uncontrolled phagocytosis of normal hemopoietic cells by activated histiocytes in bone marrow is collectively referred to as hemophagocytic lymphohistiocytosis. CASE: We present a case of hemophagocytic lymphohistiocytosis associated with herpes simplex virus-2 infection in the second trimester. Cytopenia, elevated C-reactive protein, ferritin, soluble interleukin-2 receptor, and interleukin-6 with high-grade fever were observed following genital herpes infection, and the existence of hemophagocytes in bone marrow confirmed the diagnosis of hemophagocytic lymphohistiocytosis. Corticosteroid therapy failed to arrest the hemophagocytic process, whereas cyclosporin A was effective. The patient delivered a healthy infant after remission and has not experienced exacerbation. CONCLUSION: It is often important to take into consideration hemophagocytic lymphohistiocytosis when encountering cytopenia with high-grade fever. Cyclosporin A was a safe and available strategy for this corticosteroid-resistant case.

Immunomodulatory effect of gold sodium thiomalate on murine acquired immunodeficiency syndrome

Induction of IL‐2 production and increased expression of CD25 were observed in C57BL/10 mice after weekly treatment with gold sodium thiomalate (GST). LP‐BM5 murine leukemia virus (MuLV) infected mice treated with GST survived longer, had less cervical lymph node swelling, lower spleen weight, and fewer abnormalities in the expression of the cell surface markers, CD4, CD8a and CD45R/B220 on spleen cells than those that were not treated with GST. Thus, GST treatment may be beneficial through a decrease in disease progression via IL‐2 induction in MuLV infected mice. This may have application in human immunodeficiency virus‐infected individuals.

Immunosuppression with tacrolimus improved reproductive outcome of women with repeated implantation failure and elevated peripheral blood th1/th2 cell ratios

We evaluated the clinical efficacy of immunosuppressive treatment with tacrolimus for repeated implantation failure (RIF) patients who have elevated in T helper (Th1)/Th2 cytokine producing cell ratios.

Efficacy of double vaccination with the 2009 pandemic influenza A (H1N1) vaccine during pregnancy.

OBJECTIVE: To evaluate the efficacy of double vaccination with the 2009 pandemic influenza A (H1N1) vaccine during pregnancy. METHODS: A study of the 2009 H1N1 vaccine was conducted in 128 pregnant women, who were between 8 and 32 weeks of gestation in October 2009, to monitor the immune response to vaccination and the change in antibody positivity rate and to assess the immune response. Furthermore, the study aimed to assess the changes in these parameters after the first and second vaccination, monitor the maintenance of antibody titers in maternal blood, assess antibody transfer to umbilical cord blood, and evaluate the vaccine. RESULTS: The antibody positivity rate increased from 7.2% before vaccination to 89.5% after the second vaccination. The vaccine was efficacious, producing a sufficient immune response in 90% of patients, regardless of the stage of gestation. The antibody titers were maintained until delivery, and were higher in umbilical cord blood at delivery than in maternal blood. Although the second vaccination increased the antibody titers in 27% of patients, and the antibody titers in maternal and umbilical cord blood at delivery tended to be higher in the double vaccination group than in the single, the differences were not statistically significant. CONCLUSION: Single vaccination induces sufficient immune response and transfer of immunity to the fetus in pregnant women with no pre-existing antibodies. LEVEL OF EVIDENCE: III

Influenza vaccination during pregnancy and its usefulness to mothers and their young infants

The current approach to protecting pregnant women from influenza infection and serious influenza-related complications is vaccination. It is, therefore, critical to evaluate the vaccines safety, immunogenicity, and protection efficacy during pregnancy. However, because it is affected by previous influenza vaccination or infection, the efficacy of the seasonal trivalent inactivated influenza vaccine is difficult to evaluate in pregnant women. The A/H1N1pdm pandemic in 2009 provided us with the opportunity to evaluate the immunogenicity of the influenza vaccine unaffected by previous vaccinations or infections. Vaccination with inactivated influenza virus during pregnancy elicited neutralizing antibody titers that were sufficient and comparable to those of naturally infected individuals. Furthermore, post-pandemic surveys provided a wealth of definitive information on vaccine efficacy and safety. In addition, transplacental transfer of antibodies following vaccination protected newborn infants against influenza infection. With reports showing the effectiveness of influenza vaccine during pregnancy, it is suggested that influenza vaccination benefits both mothers and their young infants.

Early plasmapheresis followed by high‐dose γ‐globulin treatment saved a severely Rho‐incompatible pregnancy

An alloimmunized pregnancy induces anemia in the fetus and can ultimately lead to fetal hydrops and intrauterine fetal death. A woman with a severe Rho‐incompatible pregnancy had experienced frequent pregnancies with fetomaternal transfusion without receiving RhIg and had high anti‐D antibody titers present from early pregnancy. We succeeded in long‐term inhibition of antibody production using plasmapheresis followed by high‐dose γ‐globulin treatment in early pregnancy. J. Clin. Apheresis, 2011.

Clinical features and pregnancy outcome in antiphospholipid syndrome patients with history of severe pregnancy complications

Abstract Objective. To clarify the clinical significance of antiphospholipid antibody (aPL) profile in patients with obstetric antiphospholipid syndrome (APS). Methods. Clinical records of 13 pregnant patients (15 pregnancies) with obstetrical APS were reviewed over 10 years. Patients who met the Sapporo Criteria fully were studied, whereas those with only early pregnancy loss were excluded. In addition to classical aPL: lupus anticoagulant (LA), anticardiolipin antibody (aCL), and anti-β2-glycoprotein I (aβ2GPI); phosphatidylserine-dependent anti-prothrombin antibody (aPS/PT) and kininogen-dependent anti-phosphatidylethanolamine antibody (aPE) were also examined in each case. Results. Cases were divided into two groups according to patient response to standard treatment: good and poor outcome groups. All cases with poor outcome presented LA, with IgG aβ2GPI and IgG aPS/PT were also frequently observed. IgG aPE did not correlate with pregnancy outcome. Conclusion. aPL profile may predict pregnancy outcome in patients with this subset of obstetric APS.