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51.
Ying Wang Hirokazu Kanegane Xiaochuan Wang Xiaohua Han Qian Zhang Shunying Zhao Yeheng Yu Jingyi Wang Toshio Miyawaki 《Journal of clinical immunology》2009,29(3):352-356
Introduction X-Linked agammaglobulinemia is a prototypical humoral immunodeficiency with the mutation of the Bruton’s tyrosine kinase gene.
Methods We investigated the gene mutation and clinical features of 30 Chinese X-linked agammaglobulinemia (XLA) patients from 27 families.
There were 26 mutations, including 11 novel and 15 recurrent mutations, distributing over the entire gene. The nucleotide
and amino acid aberration, 1129C>T(H333Y) and 1196T>A(I355N), in SH2 have not been reported before. Five (I355N, W124R, R520X,
I590F, G594E) of the 24 mutations not detected in the mothers receiving gene analysis were determined to be de novo. Two mutations
occurred within intronic splice-site sequences (intron5(−2)A>G, intron17(−2)A>T).
Results and Discussion There are eight mutations in the PH domain, two mutations in the SH3 domain, three mutations in the SH2 domain, one mutation
in the TH domain, and other 16 mutations in the TK domain. The mutations of protein domain is most common in TK (53%) domain
and then in PH(8%) domain. Missense and nonsense mutations were found equal in 46% of the detected mutations. All of the patients
are alive, but one died of liver cancer. Clinical features and serum Igs levels range variedly and were not correlated with
genotypes. Our results demonstrated molecular genetic characteristics of XLA in mainland China. 相似文献
52.
53.
Yuya Hashimura Kandai Nozu Hirokazu Kanegane Toshio Miyawaki Akira Hayakawa Norishige Yoshikawa Koichi Nakanishi Minoru Takemoto Kazumoto Iijima Masafumi Matsuo 《Pediatric nephrology (Berlin, Germany)》2009,24(6):1181-1186
Several studies have suggested that T cell-producing permeability factors might lead to proteinuria in minimal change nephrotic
syndrome (MCNS). However, it is still unclear whether T-cell abnormalities cause MCNS. Immune dysregulation, polyendocrinopathy,
enteropathy, X-linked (IPEX) syndrome is a rare disorder of the immune regulation system, which leads to severe autoimmune
phenomena including autoimmune enteropathy, atopic dermatitis with high levels of serum immunoglobulin E (IgE), type 1 diabetes
mellitus (T1DM), and severe infection such as sepsis, which frequently result in death within the first 2 years of life. This
disease is caused by mutations in the FOXP3 gene that result in the defective development of regulatory T (Treg) cells. This report describes a 5-year-old boy with IPEX
syndrome with a 3 bp deletion in the FOXP3 gene (c.748–750delAAG, p.250K.del) and a paucity of CD4+ CD25+ FOXP3+ T cells. The boy’s condition was complicated by MCNS in addition to many IPEX-related manifestations, such as atopic dermatitis,
T1DM, enteropathy, sepsis and hemolytic anemia. This is the first report of IPEX syndrome complicated by MCNS, and our findings
imply that Treg cell dysfunction may be crucial for the development of MCNS. 相似文献
54.
55.
56.
H Kanegane T Miyawaki A Yachie T Oh-Ishi K Bhatia G Tosato 《Leukemia & lymphoma》1999,34(5-6):603-607
Chronic active Epstein-Barr virus (EBV) infection is manifested clinically by the persistence of infectious mononucleosis-like symptoms or its complications for a prolonged period ranging from one to several years. This syndrome may include severe disease manifestations and can be fatal. The role of EBV in the pathogenesis of chronic active EBV infection has been unclear. We investigated two Japanese patients with severe chronic active EBV infection who subsequently developed EBV-positive T-cell lymphoma. We found that the patients had evidence of EBV infection in the peripheral blood CD4+ T-cells 19 and 3 months, respectively, before the T-cell lymphoma was diagnosed. The lymphomas were infected with monoclonal EBV and expressed the EBV latency genes EBNA-1, LMP-1, and LMP-2A, a virus latency pattern referred to as latency II. Genetic studies showed that the virus detected in the T-cell lymphoma was indistinguishable from the virus in the peripheral blood CD4+ T-cells. These studies support an important pathogenetic role of T-cell infection with EBV in chronic active EBV infection and in the EBV-positive T-cell lymphoma that followed. 相似文献
57.
Mary Ellen Conley Arnon Broides Vivian Hernandez-Trujillo Vanessa Howard Hirokazu Kanegane Toshio Miyawaki Sheila A. Shurtleff 《Immunological reviews》2005,203(1):216-234
Summary: Approximately 85% of patients with defects in early B‐cell development have X‐linked agammaglobulinemia (XLA), a disorder caused by mutations in the cytoplasmic Bruton's tyrosine kinase (Btk). Although Btk is activated by cross‐linking of a variety of cell‐surface receptors, the most critical signal transduction pathway is the one initiated by the pre‐B cell and B‐cell antigen receptor complex. Mutations in Btk are highly diverse, and no single mutation accounts for more than 3% of patients. Although there is no strong genotype/phenotype correlation in XLA, the specific mutation in Btk is one of the factors that influences the severity of disease. Mutations in the components of the pre‐B cell and B‐cell antigen receptor complex account for an additional 5–7% of patients with defects in early B‐cell development. Patients with defects in these proteins are clinically indistinguishable from those with XLA. However, they tend to be younger at the time of diagnosis, and whereas most patients with XLA have a small number of B cells in the peripheral circulation, these cells are not found in patients with defects in µ heavy chain or Igα. Polymorphic variants in the components of the pre‐B cell and B‐cell receptor complex, particularly µ heavy chain and λ5, may contribute to the severity of XLA. 相似文献
58.
Expression of L-selectin (CD62L) discriminates Th1- and Th2-like cytokine-producing memory CD4+ T cells. 总被引:4,自引:0,他引:4
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H Kanegane Y Kasahara Y Niida A Yachie S Sughii K Takatsu N Taniguchi T Miyawaki 《Immunology》1996,87(2):186-190
Human memory (CD45RO+) CD4+ T cells can be distinguished into two subpopulations on the basis of expression of the lymph node homing receptor, L-selectin (CD62L). In a prior study we showed that human L-selectin-positive memory T-helper (Th) cells promote the maturation of IgG- and IgA-producing cells by naive B cells. To further elucidate the contribution of memory CD4+ T cells to B-cell differentiation, human memory CD4+ T cells with or without L-selectin expression were evaluated for production of cytokines that participate in regulation of immunoglobulin production. It was found that L-selectin-positive human memory CD4+ T cells produce mainly interleukin (IL)-4 and IL-5, whereas L-selectin-negative CD4+ T cells produce mainly interferon-gamma (IFN-gamma). This profile of cytokine expression coincides with the profile that distinguishes Th1 and Th2 subsets. In contrast to the murine system, IL-10 production was similarly contributed by human L-selectin-positive and -negative memory CD4+ T-cell subpopulations. These results suggest that the human L-selectin-negative and -positive subpopulations of human memory CD4+ T cells contain Th1-like and Th2-like cytokine-producing cells, respectively. 相似文献
59.
Tomoko Toma Kazunori Mizuno Hiroyuki Okamoto Chiharu Kanegane Kazuhide Ohta Yasuhiro Ikawa Masayoshi Miura Mondo Kuroda Yo Niida Shoichi Koizumi Akihiro Yachie 《Pediatrics international》2005,47(1):32-38
Abstract Background : There is increasing concern in Japan over infants with atopic dermatitis (AD) who present with severe systemic complications, such as hypoproteinemia, electrolyte disturbances, and delayed growth and development. They are often associated with extremely increased numbers of circulating eosinophils. However, the clinical significance of eosinophil expansion has not been thoroughly investigated.
Methods : This study attempted to determine the significance of eosinophilia and eosinophil activation in infant cases of AD by comparing multiple clinical parameters, indexes of eosinophil activation, and levels of serum cytokines. CD69 expression was determined by flow cytometry. The clinical severity of AD was graded by the severity SCORing of atopic dermatitis (SCORAD) method. Patients were classified into two groups, with and without CD69 on eosinophils. Nuclear lobes were evaluated under a microscopy. Serum levels of eosinophil-derived neurotoxin (EDN), interleukin (IL)-12, IL-18, IL-4, IL-5 and interferon (IFN)-γ were determined by enzyme-linked immunosorbent assay.
Results : Patients with CD69-positive eosinophils had significantly higher numbers of eosinophils and platelets, total IgE, and eosinophil nuclear lobes. They also showed growth failure, developmental delay, low serum albumin, and electrolyte disturbances. EDN and IL-18 levels were significantly increased in this group, but the levels of IL-4, IL-5 and IL-12 were not significantly different between the two groups. IFN-γ was not detectable in all patients with AD. Surface expression of CD69 indicates intense systemic allergic inflammation induced in severe cases of AD.
Conclusions : Evaluation of eosinophil activation and early therapeutic intervention is mandatory for the treatment of severe AD during infancy. 相似文献
Methods : This study attempted to determine the significance of eosinophilia and eosinophil activation in infant cases of AD by comparing multiple clinical parameters, indexes of eosinophil activation, and levels of serum cytokines. CD69 expression was determined by flow cytometry. The clinical severity of AD was graded by the severity SCORing of atopic dermatitis (SCORAD) method. Patients were classified into two groups, with and without CD69 on eosinophils. Nuclear lobes were evaluated under a microscopy. Serum levels of eosinophil-derived neurotoxin (EDN), interleukin (IL)-12, IL-18, IL-4, IL-5 and interferon (IFN)-γ were determined by enzyme-linked immunosorbent assay.
Results : Patients with CD69-positive eosinophils had significantly higher numbers of eosinophils and platelets, total IgE, and eosinophil nuclear lobes. They also showed growth failure, developmental delay, low serum albumin, and electrolyte disturbances. EDN and IL-18 levels were significantly increased in this group, but the levels of IL-4, IL-5 and IL-12 were not significantly different between the two groups. IFN-γ was not detectable in all patients with AD. Surface expression of CD69 indicates intense systemic allergic inflammation induced in severe cases of AD.
Conclusions : Evaluation of eosinophil activation and early therapeutic intervention is mandatory for the treatment of severe AD during infancy. 相似文献
60.
Suppressor of cytokine signalling-1 gene silencing in acute myeloid leukaemia and human haematopoietic cell lines 总被引:4,自引:0,他引:4
Watanabe D Ezoe S Fujimoto M Kimura A Saito Y Nagai H Tachibana I Matsumura I Tanaka T Kanegane H Miyawaki T Emi M Kanakura Y Kawase I Naka T Kishimoto T 《British journal of haematology》2004,126(5):726-735
The aim of this study was to investigate whether the suppressor of cytokine signalling (SOCS)-1 can act as a tumour suppressor when functioning as a negative regulator of the Janus family tyrosine kinases (JAKs), which have been reported to play important roles in leukaemogenesis. For this purpose, we carried out molecular analysis of the SOCS-1 gene in human acute myeloid leukaemia (AML) and human haematopoietic cell lines. Sequencing alterations in the coding region were found in two of 90 primary AML samples and one of 17 cell lines. Hypermethylation of the SOCS-1 gene was also observed in 72% of primary cases and 52% of cell lines and aberrant methylation strongly correlated with reduced expression. Transfection of SOCS-1 into Jurkat cells harbouring the mutation and methylation suppressed cell growth at a low serum concentration. These findings indicate that SOCS-1 is frequently silenced in haematopoietic malignancies, mainly as a result of hypermethylation, and suggest that SOCS-1 may be able to function as a tumour suppressor. 相似文献