Kazuhiro Tomizawa

The inductive effect of interleukin-4 on IgG4 and IgE synthesis in human peripheral blood lymphocytes

Using murine monoclonal antibodies against human IgG subclasses, specific and sensitive ELISAs assay to quantify the four human IgG subclasses in cell culture supernaUints were established. The effect of human recombinant interleukin‐4 (IL‐4) on the regulation of IgG subclasses by normal peripheral blood lymphocytes was investigated. In addition to the enhancement of lgE synthesis. IL‐4 preferentially induced IgG4 synthesis in vitro, whereas IL‐4 had no effect on IgGl, IgG2, and IgG3 synthesis. IL‐4‐induced IgG4 production was blocked in a dose‐dependent manner by recombinant interferon‐gamma and anti‐human IL‐4 monoclonal antibody. Collectively, this data indicates that IL‐4 plays an important regulatory role in both IgG subclass and IgE synthesis.

A Japanese family of X-linked auto-immune enteropathy with haemolytic anaemia and polyendocrinopathy

Three cases of X-linked auto-immune enteropathy with haemolytic anaemia and polyendocrinopathy are described from one related Japanese kindred. Two boys had died due to severe diarrhoea accompanied by total or subtotal intestinal villous atrophy.In contrast, although one patient showed the same symptoms and had circulating IgG antibodies against enterocytes, his condition improved dramatically and he developed well following the use of cyclosporin A (CSA). CSA may be beneficial in patients with this rare disorder. Auto-immune enteropathy should be considered as a cause of protracted diarrhoea with unknown aetiology.

Distinct clonotypic Epstein-Barr virus-induced fatal lymphoproliferative disorder in a patient with Wiskott-Aldrich syndrome.

Background. Recently, reports of Epstein–Barr virus (EBV)‐induced lymphoproliferative disorders (LPD) have increased in number among immunosuppressed recipients of organ transplants. The importance of analyzing both the immunoglobulin gene and EBV termini is advocated for the investigation of pathogenetic mechanisms for clonal proliferation in EBV‐induced LPD; however, the oncogenic mechanisms of EBV‐induced LPD remain unclear. Furthermore, there are very few clonotypic studies of EBV‐induced LPD in patients with primary immunodeficiency diseases. The authors studied the clonality of an EBV‐induced fatal LPD in a 20‐year‐old patient with Wiskott‐Aldrich syndrome (WAS), an X‐linked recessive primary immunodeficiency disease.

A newly recognized point mutation in the cytochrome b558 heavy chain gene replacing alanine57 by glutamic acid, in a patient with cytochrome b positive X-linked chronic granulomatous disease

Molecular genetic analysis was performed in a patient with cytochrome b positive X-linked chronic granulomatous disease. A previous Southern blot study, using a cytochrome b heavy chain cDNA as probe, revealed a Pst I restriction fragment pattern for the cytochrome b heavy chain gene (CYBB) different to that of normal individuals. Since restriction length polymorphism with Pst I has never been observed in control individuals and no abnormal restriction fragment patterns in the patients CYBB was detected with seven other enzymes used, we focussed on the single Pst I site in the CYBB cDNA as being the only mutation site responsible for his disease. A fragment of the patients cDNA which included the Pst I site was amplified by reverse polymerase chain reaction, and loss of the Pst I site in the fragment was confirmed by incubation with Pst I. Subsequent sequence analysis of the fragment revealed a point mutation in the Pst I site (cytosine to adenine), substituting glutamic acid for alanine at position 57.

Steroid therapy for bronchopneumonia in chronic granulomatous disease.

In general, immunosuppressive agents such as corticosteroids are considered to be a contraindication for immunocompromised hosts with an active infection. Recently, however, a few cases have been reported where the obstructive lesions caused by the excessive inflammation in chronic granulomatous disease were successfully resolved with corticosteroids, resulting in a remission of the infection. As we have also experienced a case in which oral corticosteroid used in combination with antibiotics had a beneficial effect on an intractable respiratory tract infection which occurred in a patient with chronic granulomatous disease, we present the case report. Although it may be very difficult to determine the candidates, we consider that in selected cases a corticosteroid therapy with concomitant use of antibiotics will be a choice for the treatment of intractable infections in chronic granulomatous disease.

Interleukin‐4 regulates the interleukin‐2 receptors on human peripheral blood B lymphocytes

The high‐affinity interleukin‐2 (IL‐2) receptor (IL‐2R) consists of the non‐covalent association of at least two subunits, p55 and p70–75, capable of binding IL‐2 with low and intermediate affinity, respectively. We studied the effects of cytokines on the IL‐2R expressed on human peripheral blood B lymphocytes using monoclonal antibodies specific for IL‐2R p55 and IL‐2R p70–75, by means of two‐colour flow cytometric analysis. In freshly isolated peripheral blood B lymphocytes, the p55 subunit was expressed only in a small population (7.0% of CD20+ cells), whereas the p70–75 subunit was expressed in a large population (89.0% of CD20+ cells). Of the cytokines studied, interleukin‐4 (IL‐4) and interferon‐gamma (IFN‐γ) were involved in the regulation of IL‐2R on B cells. After a 2‐day incubation with IL‐4, expression of IL‐2R p55 was markedly induced, but expression of IL2‐R p70 –75 was profoundly suppressed in a dose‐dependent manner. These abilities of IL‐4 to promote IL‐2R p55 expression and suppress IL‐2R p70–75 expression were inhibited by the presence of I FN‐γ. Other cytokines, including IL‐1, IL‐2, IL‐5, and IL‐6, had little effect on the expression of these two subunits. These findings suggest that IL‐4 is a cytokine modulating B cell response through the regulation of IL‐2R.

Genetic heterogeneity in patients with X-linked recessive chronic granulomatous disease.

ABSTRACT: Genetic heterogeneity in 12 patients from 11 different families with X-linked recessive chronic granu-kHnatoas disease was studied by Southern blot analysis using cytochrome b heavy-chain cDNA as a probe. We found the abnormal restriction length fragment patterns of the cytochrome b heavy-chain gene in three families, which were not observed in healthy controls. DNA from one patient showed the abnormal patterns after digestion with several restriction enzymes. The DNA of two other patients showed the abnormality only with TaqI and Pst I. Analysis of the same family members indicated that these abnormal patterns cosegregated with the disease. The other nine patients from eight families did not have any abnormalities detectable by Southern blot analysis. Although further experimentation should be done to study the molecular genetic heterogeneity in most X-linked chronic granuloma-tous disease families (eight of 11), we were able to demonstrate at least three different types of mutations hi the cytochrome b heavy-chain gene responsible for the disease.