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Hirokazu Kanegane

Publications and source records attributed to Hirokazu Kanegane.

At least 19 recordsLinked to original sources
PubMed2006

MxA-based recognition of viral illness in febrile children by a whole blood assay.

Febrile children are often given antibiotics empirically and unnecessarily. MxA is a protein induced in peripheral lymphoid cells by type 1 interferons during active viral infection. The ability of a whole blood ELISA assay for MxA to identify children with viral illness was studied in 122 children who presented with acute onset fever and 52 age-matched healthy controls. The febrile children were divided into three groups according to their final diagnoses: etiologically diagnosed viral infection, clinically diagnosed viral infection, and bacterial infection. MxA levels in the bacterial infection group and controls were similar and low (90.9 +/- 69.7 and 76.9 +/- 63.2 ng/mL, respectively). In contrast, mean MxA levels in the two viral infection groups were higher than in both the bacterial and control groups (719.2 +/- 386.4 and 827.0 +/- 651.1, respectively). A receiver operating characteristic analysis showed that the area under the curve of the MxA level was greater than under the curves of both the white blood cell count and the C-reactive protein concentration. Whole blood assay of MxA is a clinically useful tool for diagnosing viral illness in febrile children and should help reduce use of unnecessary antibiotics.

Adolescent↗
PubMed2006

Clinical, immunological and molecular characteristics of 37 Iranian patients with X-linked agammaglobulinemia.

BACKGROUND: X-linked agammaglobulinemia (XLA) is a hereditary immunodeficiency characterized by an early onset of recurrent bacterial infections, a profound deficiency of all immunoglobulin isotypes and a markedly reduced number of peripheral B lymphocytes. Eighty-five percent of the patients with this phenotype have mutations in Bruton's tyrosine kinase (BTK) gene. METHODS: To provide an informative outlook of clinical and immunological manifestations of XLA in Iran, 37 Iranian male patients with an age range of 1-34 years, followed over a period of 25 years, were studied. Twenty-four of the 37 patients were screened for BTK gene mutation using PCR-SSCP followed by direct sequencing. BTK protein expression assay was done by flow cytometry in 9 families. RESULTS: All patients first presented with infectious diseases, the most common of which were respiratory tract infections. Eighteen different mutations were identified, 13 of which were novel: IVS1+5G>C, 1896G>A, 349delA, 1618C>T, 1783T>C, 2084A>G, 1346delT, 1351delGAG, 587A>G, IVS14-1G>A, IVS3+2T>C, 1482G>A, 1975C>A. CONCLUSION: The fact that we found a great number of novel mutations in a relatively limited number of patients underlines the heterogeneity of BTK mutations in the Iranian population. The large number of new mutations indicates that extended studies in this region would be rewarding.

Adolescent↗
PubMed2006

Outcome in patients with Wiskott-Aldrich syndrome following stem cell transplantation: an analysis of 57 patients in Japan.

A total of 57 patients with Wiskott-Aldrich syndrome (WAS) were studied after undergoing stem cell transplantation (SCT) in Japan between January 1985 and December 2004. Eleven patients received transplants from human leucocyte antigen (HLA)-matched related donors, 10 from HLA-mismatched related donors, 21 from unrelated bone marrow donors, and 15 from unrelated cord blood donors. Nine of the 57 patients rejected the initial graft. The overall 5-year survival rate was 73.7% and the 5-year failure-free survival rate was 65.7% (failure was defined as rejection or death). The overall 5-year survival rates for patients receiving bone marrow and cord blood from unrelated donors were both 80.0%. Based on univariate analysis, the factors associated with poor survival were: transplantation from an HLA-mismatched related donor, patient age of more than 5 years at the time of transplantation, and a conditioning regimen other than busulfan and cyclophosphamide (BU-CY) or busulfan, cyclophosphamide and antithymocyte globulin (BU-CY-ATG). In a multivariate analysis, a conditioning regimen other than BU-CY and BU-CY-ATG was the only independent factor associated with transplantation failure. Given the improved outcome for WAS patients following transplantation from an unrelated donor, we conclude that patients with WAS should receive SCT as soon as possible after diagnosis.

Adolescent↗
PubMed2006

Open heart operation in a child with congenital heart disease and hereditary spherocytosis.

An 18-month-old girl with hereditary spherocytosis underwent closure of the ventricular septal defect, commissurotomy of the pulmonary valve, and patch angioplasty of the pulmonary trunk without previous splenectomy. No serious complications as a result of hemolysis occurred in the perioperative period. Open heart surgery can therefore be safely performed in young children with congenital heart disease and hereditary spherocytosis who have not previously undergone splenectomy.

Female↗
PubMed2006

Clinical and genetic analyses of presumed Shwachman-Diamond syndrome in Japan.

Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, and skeletal abnormalities. SBDS was identified as a causative gene for SDS in 2003, and genetic analyses of SDS have been performed. We performed genetic analysis of 13 Japanese patients with presumed SDS and found that 10 of them had SBDS mutations. Most patients had recurrent mutations (181-184TA-->CT and 258+2T-->C); however, 2 patients had unique mutations (259-1G-->A and 428C-->G). Although genetic analysis is useful for definitive diagnosis and for genetic counseling of SDS patients and families, SDS appears to be a genetically heterogeneous disorder. In addition, presumed SDS patients without SBDS mutations may be included in other disorders.

Abnormalities, Multiple↗
PubMed2006

X-linked agammaglobulinemia diagnosed in adulthood: a case report.

X-linked agammaglobulinemia (XLA) is a humoral immunodeficiency caused by mutations in Bruton's tyrosine kinase (BTK). Patients typically become symptomatic during infancy or early childhood and develop recurrent bacterial infections. We report a Japanese case of XLA diagnosed in a patient who was 27 years of age and who had no history of severe infection. The patient's serum immunoglobulin (Ig) G, IgA, and IgM levels were 132,7, and 17 mg/dL, respectively. The percentage of positive cells for CD19 and CD20 was 0.03% and 0.02%, respectively. The patient's brother and sister had no abnormalities. Flow cytometric analysis showed a partially reduced expression of BTK protein in the patient's peripheral monocytes. Sequencing of the BTK. gene revealed a missense mutation (230C>T,T33I). Given this data, this patient was diagnosed as having rare, late onset XLA with a missense mutation in the BTK gene.

Adult↗
PubMed2005

X-linked lymphoproliferative disease associated with hypogammaglobulinemia and growth-hormone deficiency.

X-linked lymphoproliferative disease is a rare immunodeficiency disorder characterized by extreme vulnerability to Epstein-Barr virus, dysgammaglobulinemia, and very high incidence of lymphoma. Growth-hormone deficiency has been described in rare cases to be associated with certain immunodeficiencies, such as X-linked agammaglobulinemia. We report a first case with X-linked lymphoproliferative disease associated with hypogammaglobulinemia and growth-hormone deficiency, which was confirmed by SAP gene mutation. The patient's mutation is novel. He is also the first patient with X-linked lymphoproliferative disease to be reported from Saudi Arabia. The patient's Btk expression and BTK gene were normal. Patients with hypogammaglobulinemia and GH deficiency should be considered to have not only X-linked agammaglobulinemia, but also X-linked lymphoproliferative disease.

Child↗
PubMed2005

Membranoproliferative glomerulonephritis in a patient with X-linked agammaglobulinemia.

Immune complex and complement systems play an important role in membranoproliferative glomerulonephritis (MPGN). X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by severe hypogammaglobulinemia. We report the case of an XLA patient who developed MPGN during an intravenous immunoglobulin (IVIG) treatment. In this patient, the serum IgG level was maintained at more than 400 mg/dl of regular IVIG administration (2.5 g/dose/month). The patient presented with microscopic hematuria, proteinuria (U-pro/Cr: 4.0-4.2) and low serum complement levels (C3: 57.8 mg/dl) 3 years after IVIG treatment and was diagnosed histopathologically as having MPGN type III. Both hematuria and proteinuria significantly improved, and the serum complement level returned to a normal level following methylprednisolone pulse therapy. To our knowledge, this is the first case report of MPGN associated with XLA. Although it is unclear how MPGN occurred in this XLA patient, we suggest that residual humoral immunity in the patient could be associated with the development of MPGN.

Agammaglobulinemia↗
PubMed2005

Rapid detection of intracellular SH2D1A protein in cytotoxic lymphocytes from patients with X-linked lymphoproliferative disease and their family members.

Mutations in the SH2D1A gene have been described in most patients with the clinical syndrome of X-linked lymphoproliferative disease (XLP). The diagnosis of XLP is still difficult given its clinical heterogeneity and the lack of a readily available rapid diagnostic laboratory test, particularly in patients without a family history of XLP. XLP should always be a consideration in males with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH). Four-color flow cytometric analysis was used to establish normal patterns of SH2D1A protein expression in lymphocyte subsets for healthy subjects. Three of 4 patients with XLP, as confirmed by the detection of mutations in the SH2D1A gene, had minimal intracellular SH2D1A protein in all cytotoxic cell types. The remaining patient lacked intracellular SH2D1A protein in CD56+ natural killer (NK) and T lymphocytes and had an abnormal bimodal pattern in CD8+ T cells. Carriers of SH2D1A mutations had decreased SH2D1A protein staining patterns compared with healthy controls. Eleven males with clinical syndromes consistent with XLP, predominantly EBV-HLH, had patterns of SH2D1A protein expression similar to those of healthy controls. Four-color flow cytometry provides diagnostic information that may speed the identification of this fatal disease, differentiating it from other causes of EBV-HLH.

Adolescent↗
PubMed2005

X-linked lymphoproliferative syndrome presenting with systemic lymphocytic vasculitis.

X-linked lymphoproliferative syndrome (XLP) is a rare, often fatal, primary immunodeficiency disease characterized by an abnormal response to Epstein-Barr virus (EBV) infection. The gene responsible for XLP has been identified as SH2D1A/DSHP/SLAM-associated protein (SAP). The major clinical manifestations include fulminant infectious mononucleosis, lymphoproliferative disorder, and dysgammaglobulinemia. Affected males uncommonly present with lymphocytic vasculitis in addition to aplastic anemia. In this study, we describe a Japanese XLP patient who presented with hypogammaglobulinemia following acute EBV-induced infectious mononucleosis in the infancy and later had systemic lymphocytic vasculitis and hemophagocytic lymphohistiocytosis in the adulthood, which resolved by steroid pulse therapy. The patient's SAP gene was found to harbor a missense mutation (His8Asp), presumably resulting in defective expression of SAP in T cells. Biopsy specimens of lung and skin disclosed that CD8+ T cells predominantly infiltrated vascular vessels. However, immunohistochemical examination showed that EBV-infected cells were not identifiable in the vessels. We propose that T-cell-mediated immune dysregulation in XLP can cause vasculitis by EBV infection-unrelated mechanism.

Adult↗
PubMed2005

Proposed guidelines for diagnosing chronic active Epstein-Barr virus infection.

Since the initial report of unusual manifestations possibly associated with chronic active Epstein-Barr virus (EBV) infection (CAEBV), nearly three decades have passed. During this period, reported cases with this entity have dramatically increased in the world. Additionally, recent development of diagnostic procedures, including molecular biological and immunological techniques, have provided us with the ability to define certain diseases, especially malignant disorders. Guidelines, derived mainly from the current literature and recent experiences with CAEBV in Japan, for diagnosing CAEBV are proposed to clarify this enigmatic disease.

Acute Disease↗
PubMed2005

Severe neutropenia in Japanese patients with x-linked agammaglobulinemia.

X-linked agammaglobulinemia (XLA) is clinically characterized by recurrent bacterial infections during early infancy. Although it is not a phagocytic disorder, XLA is sometimes associated with neutropenia. We conducted a nation-wide survey to determine the frequency of neutropenia among Japanese XLA patients. Responses were received from 87 (86%) of 101 patients in which BTK mutations were previously identified, and of these, 16 (18%) had neutropenia. All episodes of neutropenia occurred before initiation of intravenous immunoglobulin (IVIG) replacement therapy. Two XLA patients died of multiple organ failure caused by severe neutropenia and Pseudomonas sepsis before initiation of IVIG replacement therapy. These results suggest that, in some cases, severe bacterial infections in XLA patients might be caused not only by antibody deficiencies but also by neutropenia.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2005

Ganciclovir therapy for congenital cytomegalovirus infection in six infants.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is common, and its morbidity rate is high. Ganciclovir (GCV) treatment has been used for congenital CMV infection, but there are few reports on viral loads associated with GCV therapy. METHODS: A real-time PCR assay was used to monitor viral load in 6 cases of symptomatic CMV infection that received GCV therapy. Initially GCV was given at a dose of 5-12 mg/kg/d for 2-7 weeks. In 2 cases, additional doses were given as symptoms returned. RESULTS: After GCV administration, active signs of chorioretinitis, thrombocytopenia and anemia disappeared or improved in all cases. During GCV therapy, viral loads decreased while patients improved clinically and increased again when GCV therapy was stopped. Although CMV DNA continued to be detectable for a long period, clinical findings did not always worsen. In 2 cases, an improvement of hearing loss was observed. CONCLUSION: GCV therapy transiently suppresses the CMV concentrations. Subsequent increases of viral titers do not appear to be correlated with the clinical course or neurologic outcome.

Cytomegalovirus↗