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Naoyasu Ueda,
Hiroshi Tsukamoto,
Hiroki Mitoma,
Masahiro Ayano,
Atsushi Tanaka,
Shun-Ichiro Ohta,
Yasushi Inoue, Yojiro Arinobu,
Hiroaki Niiro,
Koichi Akashi,
Takahiko Horiuchi
[show abstract]
[hide abstract]
ABSTRACT: : Anti-tumor necrosis factor α (anti-TNF-α) agents have been successfully applied for the treatment of rheumatoid arthritis, Crohn's disease, and other chronic inflammatory diseases. Not only the neutralization of soluble TNF-α but also the effect on transmembrane TNF-α is important mechanisms of action of anti-TNF-α agents. This study investigated the cytotoxic effects of new anti-TNF-α agents, certolizumab pegol and golimumab, which are mediated by transmembrane TNF-α.
: Transmembrane TNF-α-expressing Jurkat T cells that did not express TNF receptors were used. The binding ability of each anti-TNF-α agent to transmembrane TNF-α, antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and the apoptotic effect were examined.
: Certolizumab pegol and golimumab bound to transmembrane TNF-α. Golimumab induced antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, which was comparable to infliximab and adalimumab. However, certolizumab pegol did not induce antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity. Certolizumab pegol directly induced nonapoptotic cell death in transmembrane TNF-α-expressing cells. Golimumab induced a weaker apoptotic effect than infliximab and adalimumab.
: The cytotoxic effects of anti-TNF-α agents on TNF-α-expressing cells are considered to be associated with the clinical effect of these agents on granulomatous diseases. The direct cytotoxic effect of certolizumab pegol on TNF-α-producing cells may contribute to its clinical efficacy in Crohn's disease. Golimumab may be less effective for granulomatous diseases.
Inflammatory Bowel Diseases 05/2013; 19(6):1224-31. · 4.86 Impact Factor
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Naoyasu Ueda,
Yasushi Inoue,
Daisuke Himeji,
Yoshiya Shimao,
Kensuke Oryoji,
Hiroki Mitoma, Yojiro Arinobu,
Hiroaki Niiro,
Hiroshi Tsukamoto,
Takahiko Horiuchi,
Akira Ueda,
Koichi Akashi
[show abstract]
[hide abstract]
ABSTRACT: Early diagnosis is crucial for effective treatment of Wegener’s granulomatosis, although this disease shows only atypical
symptoms in the primary stage. This report describes a patient suspected of having a malignancy based on integrated 18F-fluorodeoxyglucose
positron emission tomography/computed tomography (PET/CT), which showed increased uptake in pulmonary nodules and nasopharyngeal
mucosa. Integrated PET/CT is therefore considered to be useful to confirm the distribution and determine the optimal site
for biopsy.
KeywordsWegener’s granulomatosis-Integrated 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT)-Diagnosis-Nasopharyngeal biopsy
Modern Rheumatology 04/2012; 20(2):205-209. · 1.58 Impact Factor
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Hiroaki Niiro,
Siamak Jabbarzadeh-Tabrizi,
Yoshikane Kikushige,
Takahiro Shima,
Kumiko Noda,
Shun-Ichiro Ota,
Hirofumi Tsuzuki,
Yasushi Inoue, Yojiro Arinobu,
Hiromi Iwasaki,
Shinji Shimoda,
Eishi Baba,
Hiroshi Tsukamoto,
Takahiko Horiuchi,
Tadayoshi Taniyama,
Koichi Akashi
[show abstract]
[hide abstract]
ABSTRACT: The aberrant regulation of B-cell receptor (BCR) signaling allows unwanted B cells to persist, thereby potentially leading to autoimmunity and B-cell malignancies. Casitas B-lineage lymphoma (Cbl) proteins suppress BCR signaling; however, the molecular mechanisms that control Cbl function in human B cells remain unclear. Here, we demonstrate that CIN85 (c-Cbl interacting protein of 85 kDa) is constitutively associated with c-Cbl, Cbl-b, and B-cell linker in B cells. Experiments using CIN85-overexpressing and CIN85-knockdown B-cell lines revealed that CIN85 increased c-Cbl phosphorylation and inhibited BCR-induced calcium flux and phosphorylation of Syk and PLCγ2, whereas it did not affect BCR internalization. The Syk phosphorylation in CIN85-overexpressing and CIN85-knockdown cells was inversely correlated with the ubiquitination and degradation of Syk. Moreover, CIN85 knockdown in primary B cells enhanced BCR-induced survival and growth, and increased the expression of BcLxL, A1, cyclin D2, and myc. Following the stimulation of BCR and Toll-like receptor 9, B-cell differentiation- associated molecules were up-regulated in CIN85-knockdown cells. Together, these results suggest that CIN85 is required for Cbl-mediated regulation of BCR signaling and for downstream events such as survival, growth, and differentiation of human B cells.
Blood 03/2012; 119(10):2263-73. · 9.90 Impact Factor
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Tetsuro Yamamoto,
Takahiko Horiuchi,
Hisaaki Miyahara,
Shigeru Yoshizawa,
Junichi Maehara,
Eisuke Shono,
Kazuto Takamura,
Haruhisa Machida,
Kaoru Tsujioka,
Takehiko Kaneko, [......],
Yoshihiro Kasamatsu,
Akihito Hara, Yojiro Arinobu,
Yasushi Inoue,
Hiroaki Niiro,
Yoichiro Kashiwagai,
Shin-Ichi Harashima,
Tomoko Tahira,
Hiroshi Tsukamoto,
Koichi Akashi
[show abstract]
[hide abstract]
ABSTRACT: The molecular bases and clinical features of hereditary angioedema (HAE) have not been systematically documented in Japan or in other Asian countries. Thus, the authors researched the genetic and clinical characteristics of Japanese patients with HAE.
The authors analyzed the CIINH gene for mutations in 13 unrelated Japanese patients with HAE by means of the polymerase chain reaction and nucleotide sequencing. In addition, the authors searched the literature from January 1969 to October 2010 on Japanese patients with HAE.
Seven of the mutations found were novel, including 4 missense mutations (8728T>G, 8831C>A, 16661T>G and 16885C>A), 2 frameshift mutations (2281_2350del70, 14158delT) and 1 large deletion (at least 1 kb-length deletion including exon 4), whereas 6 mutations had previously been reported in European populations.
The genetic and clinical characteristics in Japanese patients with HAE may be similar to those in Western patients although our sample size is small and the authors identified 7 novel mutations.
The American Journal of the Medical Sciences 09/2011; 343(3):210-4. · 1.39 Impact Factor
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Arerugī = [Allergy] 07/2011; 60(7):817-22.
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Hiroshi Tsukamoto,
Koji Nagafuji,
Takahiko Horiuchi,
Hiroki Mitoma,
Hiroaki Niiro, Yojiro Arinobu,
Yasushi Inoue,
Kentaro To,
Toshihiro Miyamoto,
Hiromi Iwasaki,
Takanori Teshima,
Mine Harada,
Koichi Akashi
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study is to evaluate the mechanism of long-term effect of autologous haematopoietic stem cell transplantation (ASCT) in treatment of SSc.
Eleven patients (three males and eight females) with SSc were enrolled. Blood mononuclear cells were harvested after mobilization treatment with CYC and G-CSF. CD34+ haematopoietic stem/progenitor cell fractions were purified and cryopreserved. Patients were transplanted with > 2 × 10(6)/kg autologous CD34+ cells after high-dose CYC (50 mg/kg for 4 days) conditioning. Immune reconstitution was evaluated serially by analysing lymphocyte subpopulations for 36 months.
Progressive improvement of skin sclerosis has been observed for 3 years in most of the patients. The serum level of anti-Scl-70, an auto-antibody specific to SSc, was progressively decreased after ASCT. Improvement of skin sclerosis was significantly associated with the change in the serum anti-Scl-70 level after ASCT at 36 months. Serum levels of KL-6 and surfactant protein D, indicators for interstitial pneumonia activity, were also significantly decreased. The number of CD8+ T cells immediately recovered within a month after ASCT, while the number of CD4+ T cells remained low for >36 months post-transplant. The majority of CD4+ cells were memory but not naïve T cells, and regulatory CD4+ T cells were not recovered. Th1/Th2 ratio was significantly increased after ASCT.
ASCT with purified CD34+ cells was effective in controlling the disease activity of SSc. Th1/Th2 ratio was significantly increased for at least 3 years after ASCT.
Rheumatology (Oxford, England) 12/2010; 50(5):944-52. · 4.24 Impact Factor
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Naoyasu Ueda,
Yasushi Inoue,
Daisuke Himeji,
Yoshiya Shimao,
Kensuke Oryoji,
Hiroki Mitoma, Yojiro Arinobu,
Hiroaki Niiro,
Hiroshi Tsukamoto,
Takahiko Horiuchi,
Akira Ueda,
Koichi Akashi
[show abstract]
[hide abstract]
ABSTRACT: Early diagnosis is crucial for effective treatment of Wegener's granulomatosis, although this disease shows only atypical symptoms in the primary stage. This report describes a patient suspected of having a malignancy based on integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), which showed increased uptake in pulmonary nodules and nasopharyngeal mucosa. Integrated PET/CT is therefore considered to be useful to confirm the distribution and determine the optimal site for biopsy.
Modern Rheumatology 12/2009; 20(2):205-9. · 1.58 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Basophils and mast cells are major players in the progression of allergic disorders. Although both cell types originate from hematopoietic stem cells, their lineage commitment pathways and mechanisms have been unsolved issues in hematology. Recent advances in the multicolor FACS system enable the prospective isolation of progenitor populations whose readouts are restricted to basophil and/or mast cell lineages. These newly-isolated progenitor subsets are helpful to understand the developmental machinery of basophil and mast cell lineages, leading to the possible exploitation of a novel therapeutic strategy for allergic and autoimmune disorders. In this review, we summarize the recent progress in our understanding of the basophil/mast cell ontogeny on a cellular basis.
Allergology International 02/2009; 58(1):21-8.
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[show abstract]
[hide abstract]
ABSTRACT: We report the case of a 38-year-old female patient with systemic lupus erythematosus (SLE) who developed acquired hemophilia caused by factor VIII (FVIII) inhibitors. She manifested spontaneous bleeding symptoms such as ecchymoses and hematuria. Laboratory findings showed an isolated prolongation of the activated partial thromboplastin time, reduced FVIII activity, and a high titer of FVIII inhibitors. She was successfully treated with oral predonisolone and cyclosporine in combination with steroid and cyclophosphamide pulse therapy.
Modern Rheumatology 07/2008; 18(5):511-5. · 1.58 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: The zinc finger transcription factor GATA-1 requires direct physical interaction with the cofactor friend of GATA-1 (FOG-1) for its essential role in erythroid and megakaryocytic development. We show that in the mast cell lineage, GATA-1 functions completely independent of FOG proteins. Moreover, we demonstrate that FOG-1 antagonizes the fate choice of multipotential progenitor cells for the mast cell lineage, and that its down-regulation is a prerequisite for mast cell development. Remarkably, ectopic expression of FOG-1 in committed mast cell progenitors redirects them into the erythroid, megakaryocytic, and granulocytic lineages. These lineage switches correlate with transcriptional down-regulation of GATA-2, an essential mast cell GATA factor, via switching of GATA-1 for GATA-2 at a key enhancer element upstream of the GATA-2 gene. These findings illustrate combinatorial control of cell fate identity by a transcription factor and its cofactor, and highlight the role of transcriptional networks in lineage determination. They also provide evidence for lineage instability during early stages of hematopoietic lineage commitment.
Journal of Experimental Medicine 04/2008; 205(3):611-24. · 13.85 Impact Factor
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Yojiro Arinobu,
Shin-ichi Mizuno,
Yong Chong,
Hirokazu Shigematsu,
Tadafumi Iino,
Hiromi Iwasaki,
Thomas Graf,
Robin Mayfield,
Susan Chan,
Philippe Kastner,
Koichi Akashi
[show abstract]
[hide abstract]
ABSTRACT: A hierarchical hematopoietic development with myeloid versus lymphoid bifurcation has been proposed downstream of the multipotent progenitor (MPP) stage, based on prospective isolation of progenitors capable of generating only myeloerythroid cells (common myeloid progenitor, CMP) or only lymphocytes (common lymphoid progenitor, CLP). By utilizing GATA-1 and PU.1 transcription factor reporters, here we identified progenitor populations that are precursors for either CMPs or CLPs. Two independent populations expressing either GATA-1 or PU.1 resided within the CD34(+)Sca-1(+)c-Kit(+) MPP fraction. The GATA-1(+) MPP displayed potent myeloerythroid potential without giving rise to lymphocytes, whereas the PU.1(+) MPP showed granulocyte/monocyte/lymphoid-restricted progenitor activity without megakaryocyte/erythroid differentiation. Furthermore, GATA-1(+) and PU.1(+) MPPs possessed huge expansion potential and differentiated into the original CMPs and CLPs, respectively. Thus, the reciprocal activation of GATA-1 and PU.1 primarily organizes the hematopoietic lineage fate decision to form the earliest hematopoietic branchpoint that comprises isolatable myeloerythroid and myelolymphoid progenitor populations.
Cell stem cell 11/2007; 1(4):416-27. · 23.56 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: The transcription factor T-bet was identified in CD4(+) T cells, and it controls interferon gamma production and T helper type 1 cell differentiation. T-bet is expressed in certain other leukocytes, and we recently showed (Lord, G.M., R.M. Rao, H. Choe, B.M. Sullivan, A.H. Lichtman, F.W. Luscinskas, and L.H. Glimcher. 2005. Blood. 106:3432-3439) that it regulates T cell trafficking. We examined whether T-bet influences homing of mast cell progenitors (MCp) to peripheral tissues. Surprisingly, we found that MCp homing to the lung or small intestine in T-bet(-/-) mice is reduced. This is reproduced in adhesion studies using bone marrow-derived MCs (BMMCs) from T-bet(-/-) mice, which showed diminished adhesion to mucosal addresin cellular adhesion molecule-1 (MAdCAM-1) and vascular cell adhesion molecule-1 (VCAM-1), endothelial ligands required for MCp intestinal homing. MCp, their precursors, and BMMCs do not express T-bet, suggesting that T-bet plays an indirect role in homing. However, adoptive transfer experiments revealed that T-bet expression by BM cells is required for MCp homing to the intestine. Furthermore, transfer of WT BM-derived dendritic cells (DCs) to T-bet(-/-) mice restores normal MCp intestinal homing in vivo and MCp adhesion to MAdCAM-1 and VCAM-1 in vitro. Nonetheless, T-bet(-/-) mice respond vigorously to intestinal infection with Trichinella spiralis, eliminating a role for T-bet in MC recruitment to sites of infection and their activation and function. Therefore, remarkably, T-bet expression by DCs indirectly controls MCp homing to mucosal tissues.
Journal of Experimental Medicine 03/2007; 204(2):431-9. · 13.85 Impact Factor
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[show abstract]
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ABSTRACT: The mechanism of lineage specification in multipotent stem cells has not been fully understood. We recently isolated progenitors with the eosinophil, basophil, or mast cell lineage potential, all of which originate from granulocyte/monocyte progenitors (GMPs). By using these prospectively purified progenitors, we show here that the expression timing of GATA-2 and CCAAT enhancer-binding protein alpha (C/EBPalpha) can differentially control their lineage commitment. The expression of GATA-2 instructed C/EBPalpha-expressing GMPs to commit exclusively into the eosinophil lineage, while it induced basophil and/or mast cell lineage commitment if C/EBPalpha was suppressed at the GMP stage. Furthermore, simply by switching the order of C/EBPalpha and GATA-2 transduction, even lymphoid-committed progenitors recaptured these developmental processes to be reprogrammed into each of these lineages. We propose that the order of expression of key transcription factors is critical for their interplay to selectively drive lineage specification programs, by which stem cells could generate multiple lineage cells in a hierarchical manner.
Genes & Development 12/2006; 20(21):3010-21. · 11.66 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Basophils and mast cells, which are selectively endowed with the high-affinity IgE receptor and mediate a range of adaptive and innate immune responses, have an unknown developmental relationship. Here, by evaluating the expression of the beta7 integrin, a molecule that is required for selective homing of mast cell progenitors (MCPs) to the periphery, we identified bipotent progenitors that are capable of differentiating into either cell type in the mouse spleen. These basophil/mast cell progenitors (BMCPs) gave rise to basophils and mast cells at the single-cell level and reconstituted both mucosal and connective tissue mast cells. We also identified the basophil progenitor (BaP) and the MCP in the bone marrow and the gastrointestinal mucosa, respectively. We further show that the granulocyte-related transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) plays a primary role in the fate decision of BMCPs, being expressed in BaPs but not in MCPs. Thus, circulating basophils and tissue mast cells share a common developmental stage at which their fate decision might be controlled principally by C/EBPalpha.
Proceedings of the National Academy of Sciences 01/2006; 102(50):18105-10. · 9.68 Impact Factor
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Hiromi Iwasaki,
Chamorro Somoza,
Hirokazu Shigematsu,
Estelle A Duprez,
Junko Iwasaki-Arai,
Shin-Ichi Mizuno, Yojiro Arinobu,
Kristin Geary,
Pu Zhang,
Tajhal Dayaram,
Maris L Fenyus,
Shannon Elf,
Susan Chan,
Philippe Kastner,
Claudia S Huettner,
Richard Murray,
Daniel G Tenen,
Koichi Akashi
[show abstract]
[hide abstract]
ABSTRACT: The PU.1 transcription factor is a key regulator of hematopoietic development, but its role at each hematopoietic stage remains unclear. In particular, the expression of PU.1 in hematopoietic stem cells (HSCs) could simply represent "priming" of genes related to downstream myelolymphoid lineages. By using a conditional PU.1 knock-out model, we here show that HSCs express PU.1, and its constitutive expression is necessary for maintenance of the HSC pool in the bone marrow. Bone marrow HSCs disrupted with PU.1 in situ could not maintain hematopoiesis and were outcompeted by normal HSCs. PU.1-deficient HSCs also failed to generate the earliest myeloid and lymphoid progenitors. PU.1 disruption in granulocyte/monocyte-committed progenitors blocked their maturation but not proliferation, resulting in myeloblast colony formation. PU.1 disruption in common lymphoid progenitors, however, did not prevent their B-cell maturation. In vivo disruption of PU.1 in mature B cells by the CD19-Cre locus did not affect B-cell maturation, and PU.1-deficient mature B cells displayed normal proliferation in response to mitogenic signals including the cross-linking of surface immunoglobulin M (IgM). Thus, PU.1 plays indispensable and distinct roles in hematopoietic development through supporting HSC self-renewal as well as commitment and maturation of myeloid and lymphoid lineages.
Blood 10/2005; 106(5):1590-600. · 9.90 Impact Factor
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ABSTRACT: Eosinophil lineage-committed progenitors (EoPs) are phenotypically isolatable in the steady-state murine bone marrow. Purified granulocyte/monocyte progenitors (GMPs) gave rise to eosinophils as well as neutrophils and monocytes at the single cell level. Within the short-term culture of GMPs, the eosinophil potential was found exclusively in cells activating the transgenic reporter for GATA-1, a transcription factor capable of instructing eosinophil lineage commitment. These GATA-1-activating cells possessed an IL-5Ralpha(+)CD34(+)c-Kit(lo) phenotype. Normal bone marrow cells also contained IL-5Ralpha(+)CD34(+)c-Kit(lo) EoPs that gave rise exclusively to eosinophils. EoPs significantly increased in number in response to helminth infection, suggesting that the EoP stage is physiologically involved in eosinophil production in vivo. EoPs expressed eosinophil-related genes, such as the eosinophil peroxidase and the major basic protein, but did not express basophil/mast cell-related mast cell proteases. The enforced retroviral expression of IL-5Ralpha in GMPs did not enhance the frequency of eosinophil lineage read-outs, whereas IL-5Ralpha(+) GMPs displayed normal neutrophil/monocyte differentiation in the presence of IL-5 alone. Thus, IL-5Ralpha might be expressed specifically at the EoP stage as a result of commitment into the eosinophil lineage. The newly identified EoPs could be the cellular target in the treatment of a variety of disorders mediated by eosinophils.
Journal of Experimental Medicine 07/2005; 201(12):1891-7. · 13.85 Impact Factor
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Takeshi Inukai,
Toshiya Inaba,
Jinjun Dang,
Ryoko Kuribara,
Keiya Ozawa,
Atsushi Miyajima,
Wenshu Wu,
A Thomas Look, Yojiro Arinobu,
Hiromi Iwasaki,
Koichi Akashi,
Keiko Kagami,
Kumiko Goi,
Kanji Sugita,
Shinpei Nakazawa
[show abstract]
[hide abstract]
ABSTRACT: Gain and/or loss of function mediated by chimeric transcription factors generated by nonrandom translocations in leukemia is a key to understanding oncogenesis. E2A-hepatic leukemia factor (HLF), a chimeric basic region/leucine zipper (bZIP) transcription factor expressed in t(17;19)-positive leukemia cells, contributes to leukemogenesis through its potential to inhibit apoptosis. To identify physiologic counterparts of this chimera, we investigated the function of other bZIP factors that bind to the same DNA sequence recognized by E2A-HLF. Here, we show that thyrotroph embryonic factor (TEF), which shares a high level of sequence identity with HLF and recognizes the same DNA sequence, is expressed in a small fraction of each subset of hematolymphoid progenitors. When TEF was introduced into FL5.12 interleukin 3 (IL-3)-dependent cells, TEF protected the cells from apoptosis due to IL-3 deprivation. Unexpectedly, TEF also almost completely down-regulated expression of the common beta (betac) chain of cytokine receptors. Consequently, TEF-expressing cells accumulated in G(0)/G(1) phase without undergoing apoptosis. These findings suggest that TEF is one of the apoptotic regulators in hematopoietic progenitors and controls hematopoietic-cell proliferation by regulating the expression of the betac chain. In contrast, E2A-HLF promoted cell survival more efficiently than TEF but did not down-regulate betac chain expression, suggesting that E2A-HLF retains ideal properties for driving leukemic transformation.
Blood 07/2005; 105(11):4437-44. · 9.90 Impact Factor
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Chika Morita,
Takahiko Horiuchi,
Hiroshi Tsukamoto,
Nobuaki Hatta,
Yuji Kikuchi, Yojiro Arinobu,
Takeshi Otsuka,
Takuya Sawabe,
Shin-Ichi Harashima,
Kohei Nagasawa,
Yoshiyuki Niho
[show abstract]
[hide abstract]
ABSTRACT: Objective
To investigate whether a polymorphism(s) or mutation(s) in the tumor necrosis factor receptor II (TNFRII) gene is involved in the pathogenesis of systemic lupus erythematosus (SLE).Methods
All 10 exons of the TNFRII gene were analyzed by exon-specific polymerase chain reaction–single-strand conformation polymorphism, followed by nucleotide sequencing of exons that displayed aberrant bands. To analyze the function of the TNFRII polymorphisms, the full-length TNFRII complementary DNA of each allele was transfected in HeLa cells and then studied for specific binding of 125I-TNFα, as well as interleukin-6 (IL-6) production and cytotoxic activity after treatment with recombinant human TNFα.ResultsWe identified 4 polymorphisms, at codons 56, 181, 196, and 232. The latter 2 had amino acid substitutions M196R and E232K, respectively. Only the 196R allele was significantly associated with SLE in our 105 Japanese SLE patients, with an allele frequency of 20.5%, compared with 12.6% in 99 healthy controls (P = 0.0335). More importantly, using TNFRII-transfected HeLa cells, we demonstrated significantly increased IL-6 production by 196R TNFRII compared with 196M TNFRII. The cytotoxic activity induced by 196R TNFRII was also increased compared with that of 196M TNFRII. This increase was achieved without affecting the binding affinity of TNFα to TNFRII, as demonstrated by the finding that specific TNFα binding to the HeLa transfectants of 196R and 196M TNFRII was similar, with Kd values of 3.12 × 10−10M and 4.34 × 10−10M, respectively.Conclusion
These results suggest that 196R TNFRII, which transduces the signals of TNFα more effectively than does 196M TNFRII, is involved in the pathogenesis of SLE.
Arthritis & Rheumatism 11/2001; 44(12):2819 - 2827. · 7.87 Impact Factor
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Mitsuteru Akahoshi,
Hitoshi Nakashima,
Yosuke Tanaka,
Tsutomu Kohsaka,
Shuji Nagano,
Eiichi Ohgami, Yojiro Arinobu,
Kunihiro Yamaoka,
Hiroaki Niiro,
Michiya Shinozaki,
Hideki Hirakata,
Takahiko Horiuchi,
Takeshi Otsuka,
Yoshiyuki Niho
[show abstract]
[hide abstract]
ABSTRACT: Objective
To analyze the Th1/Th2 balance of peripheral Th cells in patients with systemic lupus erythematosus (SLE).Methods
The Th1:Th2 ratio was analyzed in 3 groups: SLE without proteinuria (group I; n = 23), SLE with proteinuria (group II; n = 31), and normal controls (group III; n = 24). Group II patients who had undergone renal biopsy were classified into 3 subgroups based on their renal histopathologic findings. The intracellular cytokine detection method with flow cytometry was used to quantitate Th1 and Th2 cells.ResultsThere was no difference in the mean Th1:Th2 ratio between SLE patients (groups I and II) and healthy controls (group III). However, the mean value in group II was significantly higher than those in groups I and III. Moreover, within group II, the mean value in SLE patients who had diffuse proliferative lupus nephritis (World Health Organization class IV) was especially high.Conclusion
Although SLE has been considered to be a disease in which Th2 cells predominate, the Th1/Th2 balance of peripheral Th cells in SLE patients in the present study did not show a predominance of these cells. In contrast, among SLE patients with WHO class IV lupus nephritis, there was a strong predominance of Th1.
Arthritis & Rheumatism 04/2001; 42(8):1644 - 1648. · 7.87 Impact Factor
