Hirofumi Furuta

Complications of childhood Sjögren syndrome.

Sjögren syndrome (SS) is a common disorder in adults and involves both glandular and extraglandular systems. We report here four cases of childhood SS complicated by chronic thyroiditis, interstitial nephritis or sweat gland inflammation. Additionally, in one of these cases, the central nervous system was involved. All of these complications are common in adult cases.

Extremely High Serum Level of IgE during Immunosuppressive Therapy: Paradoxical Effect of Cyclosporine A and Tacrolimus

A case of X-linked autoimmune enteropathy was successfully treated with cyclosporine A (CsA) or tacrolimus (FK506) and developed extremely high serum levels of IgE during the immunosuppressive therapy. Serum IgE levels increased from 190 to 1,000-2,500 IU/ml with CsA therapy and as high as 80,000 IU/ml with subsequent FK506 therapy. Serum IgG2 and IgG4 levels were slightly elevated compared to serum IgE levels. Thereafter, serum IgE levels progressively decreased in parallel with a reduced dosage of FK506. Total serum IgG levels and peripheral eosinophil counts, however, showed no significant changes during the course. These observations suggest that both CsA and FK506, potent immunosuppressants, could paradoxically enhance some immune responses, possibly through the action of CsA-/FK506-resistant immune systems.

Genetic Analysis of 13 Families with X-Linked Chronic Granulomatous Disease Reveals a Low Proportion of Sporadic Patients and a High Proportion of Sporadic Carriers

X-linked chronic granulomatous disease (X-CGD) is the most common type of CGD, whose responsible gene has been identified and termed as CYBB, according to the gp91-phox, a subunit of cytochrome b558. Although approximately 200 different mutations of the gp91-phox gene have been reported, no precise study of the proportion of sporadic cases in X-CGD, based on molecular genetic analysis, has been reported. We made a genetic analysis of six newly identified X-CGD patients together with that of eight previously reported X-CGD patients. The mutations newly detected were three missense mutations, two splice mutations, and one insertion of 2 bases. All of the mutations were novel. Twelve mothers (two of them came from the same family) and four maternal grandmothers from 13 different X-CGD families were available for further genetic studies. It was revealed that a proportion of sporadic patients was low and that of sporadic carriers was high. These results suggest that the mutation for the disease originates mainly from male gametes.

Improved dysgammaglobulinaemia in congenital rubella syndrome after immunoglobulin therapy: correlation with CD154 expression

Abstract A boy with congenital rubella syndrome developed dysgammaglobulinaemia with elevated serum levels of IgM. CD154 was not induced on his peripheral blood mononuclear cells when rubella virus RNA was detected in his throat swabs and peripheral blood by reverse transcriptase polymerase chain reaction. Following intravenous immunoglobulin therapy, improvement of immunoglobulin abnormalities, disappearance of rubella virus and normalisation of CD154 expression were demonstrated. Conclusion These findings implicate the efficacy of intravenous immunoglobulin therapy for dysgammaglobulinaemia in congenital rubella syndrome and a role of CD154 for a prolonged virus infection.

Elevation of serum IgE level and peripheral eosinophil count during T lymphocyte-directed gene therapy for ADA deficiency: implication of Tc2-like cells after gene transduction procedure

We have successfully carried out T-cell-directed gene therapy for a boy with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA SCID) and unexpectedly found an elevation of serum IgE level and peripheral eosinophil count during the course. More than 90% of transduced cells cultured for 7-11 days before infusion into the patient were positive for CD8 and expressed Th2-type cytokine genes such as IL-4, IL-5 and IL-13. Furthermore, CD4(+) T-depleted PBMC (peripheral blood mononuclear cells) from the patient synthesized IgE in vitro by stimulation with IL-4. Collectively, these results suggested that Tc2-like cells in the transduced cells have distinct immunological functions to help IgE synthesis and activate eosinophils.

Combined immunodeficiency, chromosomal instability, and postnatal growth deficiency in a Japanese girl

We report on an 11-year-old Japanese girl with combined immunodeficiency and chromosomal instability. She had postnatal growth deficiency and microcephaly, preaxial polydactyly of the left hand, and susceptibility to infections. Immunological studies showed marked lymphocytopenia (around 500/ll), reduced lymphocyte response to various mitogens, and reduced or absent serum IgA, IgG, and IgM. Cell biological studies of her primary skin fibroblasts demonstrated spontaneous chromosome aberrations and radiation hypersensitivity. The combination of immunodeficiency, chromosomal instability, and radiation hypersensitivity as seen in the girl is present in both ataxia-telangiectasia and Nijmegen breakage syndrome. Ataxia-telangiectasia was excluded because of differences in clinical features and laboratory data. Likewise, Nijmegen breakage syndrome is unlikely to be the case because the characteristic face, hyperpigmented spots, and mental retardation present in the syndrome were missing in the girl. Sequence analysis of a Nijmegen breakage syndrome responsible gene, NBS1, revealed no mutations. A normal NBS1 product was also demonstrated by immunoblot analysis using an anti-NBS1 antibody. We propose that the disorder in the girl represents a new combination of combined immunodeficiency and chromosomal instability.