Kazuya Yoshino

Placental transfer of IgG subclasses in a Japanese population.

Abstract Background: Maternal immunoglobulin G (IgG), transferred across the placenta to the fetus during intrauterine life, is an important component of the neonatal immunological defence mechanisms against infection. There is controversy with respect to differences in placental transfer of the different IgG subclasses, and no definite data are available on a Japanese population. Therefore, we investigated placental transfer of IgG subclasses in a Japanese population.

Detection of serum antibody by the antimitogen assay against streptococcal erythrogenic toxins: age distribution in children and the relation to Kawasaki disease

ABSTRACT: We describe a new method to measure human serum antibody against streptococcal erythrogenic toxins that uses inhibition of lymphocyte mitogenicity of the toxins as the indicator. Sera from 53% of 53 Kawasaki disease patients contained specific inhibitory activity against A toxin, whereas only 15% had serum inhibitory activity against B toxin. The specific anti-A toxin serum inhibitor was found in 10% of 118 age-matched control patients suffering from various infections and allergic diseases (p = 0.001, compared to Kawasaki disease patients). Serum inhibitory activity was detected in a small number of patients with β-hemolytic streptococcal infection (3/19) and in none of the age-matched healthy children (0/17). However, four of seven cord blood sera samples and five of 13 sera samples from healthy neonates contained the inhibitor, a result suggesting passive transfer from mothers. Most of the antimitogen-positive sera were also positive by ELISA of IgG antibody against A toxin, and IgG fractions of the positive sera remained positive in both assays. Thus, it is possible that the specific serum inhibitor detected by the antimitogen assay represents anti-A toxin antibody. The role of toxin-producing bacteria in the pathogenesis of Kawasaki disease remains to be investigated.

Suppressive effect of intravenous immunoglobulins on the activity of interleukin-1

In order to study the effect of human immunoglobulin preparations for intravenous use (IVIg) on the production and activity of interleukin-1 (IL-1) derived from monocytes, we treated cultured monocytes with IVIg and examined the lymphocyteactivating factor (LAF) activity of IL-1 in the culture supernatants. The results showed that IVIg suppressed the activity from most healthy adults and some febrile children with acute respiratory disease or Kawasaki disease. Further studies revealed that intact Ig (whole molecular Ig) did not suppress the mRNA expression of IL-1α or IL-1β in mononuclear cells, that intact Ig and pepsin-digested Ig inhibited the LAF activity of recombinant IL-1 (rIL-1) and also that intact Ig contains immunoglobulin (probably anti-IL-1 antibody) which binds with rIL-1 by dot blotting using biotin-streptavidin. These results suggest that IVIg suppresses neither IL-1 synthesis nor the release of IL-1 from monocytes but does neutralize IL-1α and IL-1β activity by binding IL-1 proteins as an anti-IL-1 antibody.

The increase of non-MHC-restricted cytotoxic cells (γδ-TCR-bearing T cells or NK cells) and the abnormal differentiation of B cells in Wiskott-Aldrich syndrome

The objective of this study was to analyze the configuration of the lymphocytes in Wiskott-Aldrich syndrome (WAS) by studying the surface antigens from nine cases using dual-color immunofluorescence analysis. All the patients showed the increase of non-MHC-restricted cytotoxic cells, namely CD3+WT31−δTCS1+ (γδ-T cell receptor (TCR)-bearing cells) and/or CD16+ natural killer cells. The γδ-TCR+ cells of WAS, however, were unique since they did not express CD5, which is present on ordinary γδ-TCR+ cells. A reduced number of CD4+ cells and an increased percentage of CD11b+Leu7+ cells within a CD8+ subset were observed in all cases. With regard to B cell subpopulations, most cases showed reduced FcϵR2-bearing B cells, despite an elevated serum IgE.

Anti-Idiotypic Antibody as a Mirror Image of the Paratope of the Original Antibody

Immunization with 2,4-dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH) produced antibodies with combining sites (paratope) which could accommodate not only the 2,4,6-trinitrophenyl (TNP) antigen but also the 4-hydroxy-3-nitrophenyl (NP) and 4-hydroxy-5-iodo-3-nitrophenyl (NIP) antigens, while immunization with NIP-KLH or TNP-KLH produced antibodies with combining sites which could accommodate only the homologous antigens. Utilizing these cross-reacting anti-hapten antibodies mentioned above, an anti-idiotypic antibody was investigated and characterized. Anti-DNP antibodies (Ab1) cross-reacted with the epitopes TNP, NP or NIP. It was also shown that heterologous anti-anti-DNP antibodies (Ab2) recognized not only the antibody which was produced by immunization with DNP-KLH, but also the antibodies produced by immunization with NIP-KLH, NP-KLH or TNP-KLH. The guinea pig anti-idiotypic antibody which we obtained using murine anti-DNP antibodies (Ab1) as antigen is therefore better defined not as an internal image of the antigen but as a mirror image of the paratope of the immunizing Ab1.

Immunological aspects of juvenile rheumatoid arthritis

This article reviews the evidence from recent studies on immunological abnormalities associated with pathophysiologic mechanisms operating in three clinical subtypes of juvenile rheumatoid arthritis (JRA) (polyarticular, pauciarticular and systemic). The main discussion is focused on three hallmarks of immunopathological studies. First, abnormalities in phenotype and function of lymphocytes from peripheral blood and inflamed synovium are discussed. The aberrations of lymphocytes are elucidated by T and B cells expressing phenotypic cell‐markers such as CD20, CD21, CD4, CD8 and DR in association with different subtypes and disease activity. The functional imbalance and impairment of T and B cells are mainly observed by abnormal proliferation and/or in vitro Ig production in response to mitogens and alloantigens. Second, because the appearance of rheumatoid factors (RF) in serum indicates that the pathogenesis of JRA may be based on the autoimmune mechanism, the prevalence of RF including IgM, IgA and IgG isotype, hidden IgM RF and cross‐reactive idiotype RF, and their characteristic properties are discussed. Moreover, specific auto‐antibodies (antinuclear antibodies and others) for JRA are illustrated in this paper. Third, the production of various pro‐inflammatory cytokines resulting in the release of tissue‐damaging chemical mediators is also discussed. This may play a central role in the generation of systemic inflammation and joint involvement in JRA.

The Suppressive Effect of Histamine on Anti-DNP Antibody Production in Mice

To clarify the effect of histamine on antibody production, histamine was injected intravenously into DNP-KLH immunized C3H/HeN female mice. The number of anti-DNP plaque-forming splenic cells decreased in immunized and histamine-injected mice. Decreased PFC responses similarly occurred in recipient mice into which Lyt-2.1 T cells obtained from histamine-injected mice were transferred before immunization. The effect of histamine is not due to inhibition on plaque formation. The results indicated that histamine induced the augmentation of suppressor T cell (Ts) function and caused the decrease of antibody production in histamine-injected mice. The maximum activity of Ts in recipient mice was obtained from mice injected with histamine 3 days before the cell transfer. The suppressive activity of histamine was not antigen specific because Ts was induced in histamine-injected, nonimmunized mice. The treatment of histamine type 2 (H2) agonist showed decreased PFC responses in the mouse as well as histamine did. When mice were treated with an H2 antagonist followed by histamine, antibody production was not reduced. The above results indicated that histamine seemed to regulate antibody production through H2 receptors on lymphocyte membranes.

Interleukin 8 in the human colostrum.

We investigated the postpartum changes in colostral interleukin (IL) 8 concentrations during the first 3 postpartum days and examined the IL-8 production of colostral cells at the levels of both protein and mRNA. Colostrum samples were obtained from healthy mothers after full-term delivery. Colostrum, supernatants, and cell lysates of cultured colostral cells were assayed for IL-8 by enzyme-linked immunosorbent assay. Reverse-transcription polymerase chain reaction was used to test uncultured colostral cells for the production of IL-8 mRNA. The colostral IL-8 concentrations, especially high on day 1 postpartum, declined abruptly during the first 3 postpartum days (mean 19.7, 10.0, and 3.0 ng/ml on days 1, 2 and 3 postpartum, respectively). Colostral cells apparently produced and secreted IL-8 in in vitro culture without stimulant, although in smaller quantities than with lipopolysaccharide stimulation. The majority of uncultured colostral cell samples expressed IL-8 mRNA, suggesting a role of colostral cells, at least in part, as a source of colostral IL-8.

Microorganisms in house dust mites in Kawasaki disease—A possible causal agent of the disease—

Until now, the etiology of Kawasaki disease has remained unknown. Furusho et al. reported that an antigen associated with house dust mites (Dermatophagoides) may be a causal agent of Kawasaki disease, because in the course of the disease serum levels of antimite (0. pteronyssinus) specific IgG, estimated by radioallergosorbent tests, were increased in the patients. Furthermore, serum total IgE and the IgE specific to D.pteronyssinus were also increased in the initial stage of the disease, while they were decreased in the late stage. They also reported that the sera IgG of the patients reacted to house dust mites in their study by using an immunofluorecent method!.’) Hamashima et aL3) suggested that Rickettsia-like particles observed in the digestive tracts of house dust mites might be the possible causal agents of Kawasaki disease, because the mites in the patients’ house contained numerous particles in comparison with healthy-house dust mites

The suppressive effect of salicylazosulfapyridine on IL-6 production by human coronary artery endothelial cells.

It is thought that prominent production of inflammatory cytokines and expression of adhesion molecules on the endothelial cells activated by unkown pathogens induce the formation of the vasculitis in Kawasaki disease (KD) . To study the anti-inflammatory effect of salicylazosulfapyridine (SASP) on the cardiovasculitis of KD, we examined the effect of SASP on IL-6 production by human coronary artery endothelial cells (HCAEC) . We used HCAEC because IL-6 production by HCAEC was greater than by human umbilical vein endothelial cells. SASP at less than 0.5 mM suppressed IL-6 production by LPS-induced HCAEC, and higher concentrations of SASP affected cell viability. On the other hand, SASP did not suppress IL-6 production by the cells stimulated with cytokines such as TNFα, IL-1 β and IL-4. Sulfapyridine and 5-aminosalicylic acid, which are degradation products of SASP, did not suppress IL-6 production.These results show that SASP may have a direct inhibitoy effect on HCAEC activated by external substances such as LPS, which may be an effective agent in the cardiovasculitis of KD.