Keisuke Shinomiya

DiGeorge syndrome with hypogammaglobulinaemia: a patient with excess suppressor T cell activity treated with fetal thymus transplantation

A male infant with DiGeorge syndrome had hypogammaglobulinaemia with a normal number of B cells. CD3(+) T cells were reduced and the CD4(+)/CD8(+) ratio was reversed. Proliferative responses of T cells to mitogens and to allogeneic cells were low. The pokeweed mitogen (PWM)-induced B cell differentiation assay revealed a higher than normal suppressor T cell activity. This suggests that some T cells had differentiated into functionally mature cells resulting in an imbalance of regulatory T cell functions and that excess suppressor activity might play a role in hypogammaglobulinaemia. Fetal thymus transplantation improved both cellular and humoral immunity. The patients susceptibility to viral and bacterial infections, proliferative response of T cells and serum Ig concentration returned to normal. The excess suppressor activity seen before transplantation disappeared. Hypocalcaemia did not improve. These results show that fetal thymus transplantation was effective not only in reconstituting cellular immunity but also in normalizing the imbalance of regulatory T cell functions in this patient with DiGeorge syndrome.

Possible role of neuraminidase in the pathogenesis of arteritis and thrombocytopenia induced in rats by Erysipelothrix rhusiopathiae.

The role of the neuraminidase produced by Erysipelothrix rhusiopathiae (E. rhusiopathiae) in the pathogenesis of arteritis and induced thrombocytopenia was examined using young and adult rats. There was a close correlation between bacterial invasion, desialation and cell infiltration in the common iliac artery. E. rhusiopathiae induced arteritis from the second and third day after inoculation with 3 X 10(8) viable bacteria in the young and adult rats, respectively. This delay with age was closely related to the increase of free sialic acid in the plasma. The sites invaded by E. rhusiopathiae coincided with the desialated lesions, and the bacteria invaded the periarterial region which was always accompanied by desialation when examined with FITC-conjugated peanut lectin. The free sialic acid in the plasma was, at least partly, considered to originate from the desialation of the arterial wall caused by E. rhusiopathiae. The platelet number decreased significantly after inoculation. The sialic acid content of the platelets prepared from circulating blood at 12 and 18 hours after inoculation showed a slight decrease and decreased further when the platelets were incubated with the bacteria. Platelets obtained from circulating blood within 24 hours after inoculation or incubated with the bacteria had demonstrated desialated sites as detected by immunofluorescent staining with FITC-conjugated peanut lectin. In conclusion, free sialic acid in the plasma was considered to be a good marker of the desialation of the arteries caused by E. rhusiopathiae, and the neuraminidase produced by the bacteria would be a key to solve the pathogenesis of the arteritis and thrombocytopenia.

IgE receptor-bearing lymphocytes in allergic and nonallergic children.

ABSTRACT: Using a monoclonal anti-human IgE receptor (FceR) antibody, the percentage of FceR(+) cells among peripheral blood lymphocytes in children with or without allergic disorders was determined. The percentage of FctR(+) cells in 63 nonallergic children was 4.3 ± 1.5%, which did not vary with age and was equal to that of adults (4.2 ± 1.2%). Allergic younger children (0–2 yr) showed a significantly higher percentage of FceR(+) cells (7.7 ± 3.0%) than nonallergic younger children (0–2 yr) (4.0 ± 1.3%, p < 0.001). Similarly, in allergic younger children, serum IgE levels (geometric mean = 58.9 IU/ml) were also significantly higher than those of nonallergic younger children (geometric mean = 2.0 IU/ml) (p < 0.01). A positive correlation between the percentages of FccR(+) cells and serum IgE levels was observed (Spearman rank = 0.88, p < 0.01)) in eight allergic younger children (0–2 yr) with serum IgE levels higher than 100 IU/ml. The increase in the percentage of FctR(+) cells in allergic younger children (0–2 yr) was not a secondary phenomenon caused by serum IgE because serum IgE levels in these children were much lower than the concentration at which IgE enhance FceR expression on lymphocytes. In conclusion, FceR(+) lymphocytes may play a regulatory role in IgE synthesis in allergic younger children (0–2 yr).

Adhesion of Erysipelothrix rhusiopathiae to Cultured Rat Aortic Endothelial Cells: Role of Bacterial Neuraminidase in the Induction of Arteritis

The adhesion of Erysipelothrix rhusiopathiae (E. rhusiopathiae) to the cultured confluent monolayer of rat aortic endothelial cells (EC) and the role of neuraminidase in the interaction between EC and E. rhusiopathiae were examined. One EC line was obtained by collagenase treatment of rat aorta. The EC showed a typical cobblestone appearance and possessed the factor VIII related antigen. When cultured more than two weeks after reaching confluence, the EC formed a vascular plexus-like appearance. E. rhusiopathiae began to adhere to EC within 2 minutes after the beginning of culture and adhered at a constant rate for 20 minutes. The adhesion of bacteria to EC was closely related to the release of sialic acid from the EC. Significantly more bacteria adhered to neuraminidase treated EC, and bacterial adhesion was inhibited dose-dependently by N-acetylneuraminic-lactose, which is the substrate of bacterial neuraminidase. It is concluded that bacterial neuraminidase plays an essential role in initiating the interaction between EC and E. rhusiopathiae, which would contribute to the genesis of arteritis.

Monoclonal anti-human IgG antibodies for quantitation of allergen-specific IgG in human sera

Eight monoclonal anti-human IgG antibodies were fully characterized and evaluated as possible reagents in solid phase radioimmunoassay for quantitating allergen-specific IgG antibody. Four monoclonal antibodies (HG24D, HG2-14, HG2-18, and HG2-25) recognize CH2 domain of human IgG and bind to human IgG fixed to microtiter plate with high affinities. These monoclonal antibodies were more suitable than polyclonal rabbit anti-human IgG antibody in Phadebas RAST for honey bee venom-specific IgG antibody. Nonspecific binding was much lower, and the slopes of standard curves were much steeper. In contrast to polyclonal antibody, the standard curve was hardly influenced by human serum IgG in sample diluent. These advantages of monoclonal antibodies that recognize CH2 domain of human IgG made it possible to quantitate egg white- and Dermatophagoides pteronyssinus-specific IgG antibodies with use of allergen disks prepared for IgE RAST. This property allows a single system to be used for measurement of IgG and IgE antibodies against clinically relevant allergens.

The use of monoclonal antibodies in demonstrating the effect of antibody heterogeneity on immune complex size

The effect of antibody heterogeneity on immune complex size was investigated by using monoclonal antibodies. Five monoclonal antibodies which bind different antigenic determinants of human serum albumin were used to produce immune complexes. When one or two different monoclonal antibodies were used, under antigen-excess, antigen-antibody equivalent, and antibody-excess conditions, hardly any immune complexes larger than mouse IgM were produced. On the other hand, in a representative experiment, when five different monoclonal antibodies were used, immune complexes larger than mouse IgM comprised 21.5% of the total antigen under antigen-antibody equivalent conditions, 18.2% under antibody-excess conditions, and 4.3% under antigen-excess conditions. These results indicate that antibody heterogeneity is one of the important factors determining immune complex size.

Standardization of the severity of exercise-induced bronchospasm in Japanese children with asthma:- A report of the Committee on Standardization of EIB, Japanese Society of Pediatric Allergy-

The correlation between the severity of asthmatic symptoms and of EIB (exercise‐induced bronchospasm) was studied by changes in PEFR (peak expiratory flow rate). This was accomplished by bicycle ergometer exercise of 12.6 kpm/kg of body weight for 6 minutes, or by treadmill exercise of 6km/h, 10% incline for 6 minutes, by children with bronchial asthma in 7 institutions in Japan (both inpatients and outpatients).

Electrophysiological studies of a child with presumed botulism

Abstract Electrophysiological studies of a child with presumed botulism showed that the amplitude of the serially and electrically elicited blink reflexes Rl, R2 and R2’ was reduced during recovery. These findings suggest a conduction block of the facial nerves. Other nerve conduction studies and an incremental response to repetitive stimulation demonstrated a block of the presynaptic neuromuscular transmission. Results of the biological tests were negative, but those of electrodiagnosis and clinical examination favored a diagnosis of botulism. A combination of electrically elicited blink reflexes and rapid repetitive stimulation of the peripheral nerves was found to be a sensitive method of assessing the integrity of neuromuscular junctions and the subclinical impairment of muscle nerves.

Serum factor in myasthenia gravis inhibits induction of "active" E by carbachol.

Abstract It has been reported that incubation with an α-adrenergic agonist ( l -phenylephrine hydrochloride) or cholinergic agonist (carbachol) increased T-lymphocyte “active” E-rosette formation. In the present work, we found that preincubation with myasthenic sera significantly inhibited active E induction by carbachol, while control sera, obtained mostly from those with neuromuscular disorders, had no effect. On the other hand, l -phenylephrine-induced active E formation was not affected by either myasthenic or control sera pretreatment. Presence of such a serum inhibitor in myasthenic patients was associated with the disease activity. Furthermore, a dose-response study showed that this inhibitor was competitive for the effect of carbachol. Heating the sera at 56°C for 30 min or dialysis against 0.9% NaCl at 4°C for 2 days did not abolish the activity. After Sephadex G-200 gel filtration of the crude sera, the same degree of inhibitory activity as was seen in the whole sera was retained at the second peak which consisted mainly of IgG.

Interaction among IgE-mediated hypersensitivity reaction, PCA reaction and delayed hypersensitivity reaction (at local skin sites of monkeys).

The effect of the IgE-mediated reaction on the passive cutaneous anaphylaxis (PCA) reaction was studied at local skin sites of monkeys, and we found that the IgE-mediated reaction appeared to enhance the PCA reaction. Interactions among IgE-mediated reaction, PCA reaction and delayed hypersensitivity reaction were also determined. Contact dermatitis induced with DNCB was utilized as the delayed hypersensitivity reaction. The IgE-mediated reactior or PCA reaction, as well as simple serum irritation, enhanced the delayed hypersensitivity reaction. It is thus assumed that the IgE-mediated reaction enhances the PCA reaction and that this in turn accelerates the delayed hypersensitivity reaction.