2002 Fiscal Year Annual Research Report

ヒトT細胞白血病ウイルスI型感染シェーグレン症候群発症予知の遺伝子診断と発症阻止

Research Project

Project/Area Number	13557042
Research Institution	Nagasaki University
Principal Investigator	江口勝美長崎大学, 大学院・医歯薬学総合研究科, 教授 (30128160)
Co-Investigator(Kenkyū-buntansha)	右田清志国立病院長崎医療センター, 臨床研究センター, 免疫研究部部長 (60264214) 中村龍文長崎大学, 大学院・医歯薬学総合研究科, 助教授 (00198219) 熊谷俊一神戸大学, 医学部, 教授 (00153346)
Keywords	シェーグレン症候群 / 遺伝子多型 / IL-10 / IL-18 / HTLV-I / GST / TAP
Research Abstract	昨年度シェーグレン症候群患者においてIL-10の遺伝子多型を解析し、ACC haplotypeがシェーグレンの発症、特に40歳以下での発症と負の相関があることを報告した。また、HTLV-1抗体陽性者はACC haplotype carrierの頻度がHTLV-1抗体陰性者に比べ低い傾向があったが、有意差はなかった。本年度は各症例の病態との関連について検討した。シェーグレン症候群患者では、ATA haplotypeが増加傾向にあるが、血清IgGが高値の症例ではATA/ATA genotypeやATA haplotypeの頻度が有意に高く、唾液腺生検でもリンパ球浸潤の多い症例はATA/ATA genotypeに多かった。以上のことから、IL-10遺伝子多型はシェーグレン症侯群の病態へも関与している可能性が示唆された。シェーグレン症候群患者においてTh1-inducer cytokineであるIL-18はIL-12とともに増加し、唾液腺細胞の破壊に関与していることが報告されており、次にこのIL-18の遺伝子多型について解析したが、有意に増加しているものはなかった。分担研究者熊谷は、シェーグレン症候群患者においてGlutathione S-transferase M1(GSTM1)、GSTT1、Transporters associated with antigen processing 1(TAP1)、TAP2の遺伝子多型を解析し、GSTM1 null(欠損者)、TAP2Bky2(codon 577:Val→Met)が有意に増加していることを見い出しているが、抗HTLV1抗体陽性シェーグレン症侯群患者では逆にGSTM1 nullや少なく、TAP2Bky2も特に増加していなかった。そして、GSTT1 nullやTAP2 0101 A alleleのものが多い傾向にあった。

Research Products

(30 results)

All Other

All Publications (30 results)

[Publications] Ida H: "Granzyme B leakage-induced cell death: a new type of activation -induced natural killer cell death"J Immunol. (accepted).
[Publications] Kita-Furuyama M: "Dendritic cells infected with adenovirus expressing the thyrotrophin receptor induce Graves' hyperthyroidism in BALB/c mice"Clin Exp Immunol. 131. 234-240 (2003)
[Publications] Yanagi K: "Immuno-gene therapy with adenoviruses expressing fms-like tyrosine kinase 3 ligand and CD40 ligand for mouse hepatoma cells in vivo"Int J Oncol. 22. 345-351 (2003)
[Publications] Ida H: "Increased levels of interleukin-18(IL-18) in patients with systemic lupus erythematosus : Comment on the article by Shibatomi et al., Reply to the editor"Arthritis Rheum. 45・5. 1411-1412 (2002)
[Publications] Yamasaki S: "Functional changes in rheumatoid fibroblast-like synovial cells through activation of peroxisome proliferator-activated receptor γ-mediated signalling"Clin Exp Immunol. 129・2. 379-384 (2002)
[Publications] Kawakami A: "Modulation of the expression of membrance-bound CD54(mCD54) and soluble from of CD54(sCD54) in endothelial cells by glucosyl transferase inhibitor;"Biochem Biophys Res Commun. 296・1. 26-31 (2002)
[Publications] Ide A: "Genetic association between interleukin-10 gene promoter region polymorphisms and type 1 diabetes age-at-onset"Hum Immunol. 63・8. 690-695 (2002)
[Publications] Kawakami A: "Involvement of apoptotic cell death in autoimmune diseases"Med Electron Microsc. 35・1. 1-8 (2002)
[Publications] Ueki Y: "NOR-1 : a nitric oxide releasing agent for calibrating low levels of nitric oxide by the chemiluminescence method"Blood Coagul Fibrinolysis. 13・2. 75-80 (2002)
[Publications] Migita K: "The role of peroxynitrite in cyclooxygenase-2 expression of rheumatoid synovium"Clin Exp Rheumatol. 20・1. 59-62 (2002)
[Publications] Nagayama Y: "A novel murine model of Graves' hyperthyroidism with intramuscular injection of adenovirus expressing the thyrotropin receptor"J Immunol. 168・6. 2789-2794 (2002)
[Publications] Kamachi M: "Regulation of apoptotic cell death by cytokines in a human salivary gland cell line : distinct and synergistic mechanisms in apoptosis induced by tumor necrosis factor α and interferon γ"J Lab Clin Med. 139・1. 13-19 (2002)
[Publications] Yonetsu K: "Sonography as a replacement for sialography for the diagnosis of salivary glands affected by Sjogren's syndrome"Ann Rheum Dis. 61・3. 276-277 (2002)
[Publications] Hashimoto Y: "Novel Immunosuppressive effect of FK506 by augmentation of T cell apoptosis"Clin Exp Immunol. 125. 19-24 (2001)
[Publications] Eguchi K: "A Poptosis in autoimmune diseases"Internal Med. 40・4. 275-284 (2001)
[Publications] Sera N: "Fas/FasL mediated apoptosis of thyrocytes in Graves' disease"Clin Exp Immunol. 124. 197-207 (2001)
[Publications] Hamasaki S: "Resistance of CD4-positive T lymphocytes to etoposide-induced apoptosis mediated by upregulation of Bcl-xL expression in patients with HTLV-I-associated myelopathy"J Neuroimmunol. 117. 143-148 (2001)
[Publications] Hirai Y: "Effects of nitric oxide on matrix metalloproteinase-2 production by rheumatoid synovial cells"Life Sci. 68. 913-920 (2001)
[Publications] Migita K: "Impaired degradation of serum amyloid A (SAA) protein by cytokine-stimulated monocytes"Clin Exp Immunol. 123・3. 408-411 (2001)
[Publications] Shibatomi K: "A Novel Role for Interleukin-18 in Human Natural Killer Cell Death"Arthritis Rheum. 44・4. 884-892 (2001)
[Publications] Kawakami A: "Role of HTLV-I Infection in the pathogenesis of Sjoren's syndrome and rheumatoid arthritis"Mod Rheumatol. 11・2. 87-90 (2001)
[Publications] Migita K: "FK506-Mediated T-Cell Apoptosis Induction"Transplant P. 33. 2292-2293 (2001)
[Publications] Yamasaki S: "Importance of NF-κB in rheumatoid synovial tissues : in situ NF-κB expression and in vitro study using cultured synovial cells"Ann Rheum Dis. 60・7. 678-684 (2001)
[Publications] Migita K: "Nitric oxide protects cultured rheumatoid synovial cells from Fas-induced apoptosis by inhibiting caspase-3"Immunology. 103. 362-367 (2001)
[Publications] Migita K: "Regulation of rheumatoid synoviocyte proliferation by endogenous p53 induction"Clin Exp Immunol. 126・2. 334-338 (2001)
[Publications] Urayama S: "New disease-modifying antirheumatic drug 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid(KE-298) selectively augments activation-induced T cell death"J Lab Clin Med. 138. 11-17 (2001)
[Publications] 江口勝美: "特集リウマチ性疾患とウイルスHTLV-I感染とリウマチ性疾患"リウマチ科. 27・3. 238-246 (2002)
[Publications] 川上純: "HTLV-I感染によるシェーグレン症候群・慢性関節リウマチの発症機序"臨床リウマチ. 13. 11-17 (2001)
[Publications] 江口勝美: "炎症におけるHTLV-I感染の役割"血液・免疫・腫瘍. 6・2. 61-71 (2001)
[Publications] Migita K: "Mechanistic Difference of Cornerstone Immunosuppressants"Fujisawa. 6 (2001)

2002 Fiscal Year Annual Research Report

ヒトT細胞白血病ウイルスI型感染シェーグレン症候群発症予知の遺伝子診断と発症阻止

Principal Investigator

江口 勝美 長崎大学, 大学院・医歯薬学総合研究科, 教授 (30128160)

Research Products

[Publications] Ida H: "Granzyme B leakage-induced cell death: a new type of activation -induced natural killer cell death"J Immunol. (accepted).

[Publications] Kita-Furuyama M: "Dendritic cells infected with adenovirus expressing the thyrotrophin receptor induce Graves' hyperthyroidism in BALB/c mice"Clin Exp Immunol. 131. 234-240 (2003)

[Publications] Yanagi K: "Immuno-gene therapy with adenoviruses expressing fms-like tyrosine kinase 3 ligand and CD40 ligand for mouse hepatoma cells in vivo"Int J Oncol. 22. 345-351 (2003)

[Publications] Ida H: "Increased levels of interleukin-18(IL-18) in patients with systemic lupus erythematosus : Comment on the article by Shibatomi et al., Reply to the editor"Arthritis Rheum. 45・5. 1411-1412 (2002)

[Publications] Yamasaki S: "Functional changes in rheumatoid fibroblast-like synovial cells through activation of peroxisome proliferator-activated receptor γ-mediated signalling"Clin Exp Immunol. 129・2. 379-384 (2002)

[Publications] Kawakami A: "Modulation of the expression of membrance-bound CD54(mCD54) and soluble from of CD54(sCD54) in endothelial cells by glucosyl transferase inhibitor;"Biochem Biophys Res Commun. 296・1. 26-31 (2002)

[Publications] Ide A: "Genetic association between interleukin-10 gene promoter region polymorphisms and type 1 diabetes age-at-onset"Hum Immunol. 63・8. 690-695 (2002)

[Publications] Kawakami A: "Involvement of apoptotic cell death in autoimmune diseases"Med Electron Microsc. 35・1. 1-8 (2002)

[Publications] Ueki Y: "NOR-1 : a nitric oxide releasing agent for calibrating low levels of nitric oxide by the chemiluminescence method"Blood Coagul Fibrinolysis. 13・2. 75-80 (2002)

[Publications] Migita K: "The role of peroxynitrite in cyclooxygenase-2 expression of rheumatoid synovium"Clin Exp Rheumatol. 20・1. 59-62 (2002)

[Publications] Nagayama Y: "A novel murine model of Graves' hyperthyroidism with intramuscular injection of adenovirus expressing the thyrotropin receptor"J Immunol. 168・6. 2789-2794 (2002)

[Publications] Kamachi M: "Regulation of apoptotic cell death by cytokines in a human salivary gland cell line : distinct and synergistic mechanisms in apoptosis induced by tumor necrosis factor α and interferon γ"J Lab Clin Med. 139・1. 13-19 (2002)

[Publications] Yonetsu K: "Sonography as a replacement for sialography for the diagnosis of salivary glands affected by Sjogren's syndrome"Ann Rheum Dis. 61・3. 276-277 (2002)

[Publications] Hashimoto Y: "Novel Immunosuppressive effect of FK506 by augmentation of T cell apoptosis"Clin Exp Immunol. 125. 19-24 (2001)

[Publications] Eguchi K: "A Poptosis in autoimmune diseases"Internal Med. 40・4. 275-284 (2001)

[Publications] Sera N: "Fas/FasL mediated apoptosis of thyrocytes in Graves' disease"Clin Exp Immunol. 124. 197-207 (2001)

[Publications] Hamasaki S: "Resistance of CD4-positive T lymphocytes to etoposide-induced apoptosis mediated by upregulation of Bcl-xL expression in patients with HTLV-I-associated myelopathy"J Neuroimmunol. 117. 143-148 (2001)

[Publications] Hirai Y: "Effects of nitric oxide on matrix metalloproteinase-2 production by rheumatoid synovial cells"Life Sci. 68. 913-920 (2001)

[Publications] Migita K: "Impaired degradation of serum amyloid A (SAA) protein by cytokine-stimulated monocytes"Clin Exp Immunol. 123・3. 408-411 (2001)

[Publications] Shibatomi K: "A Novel Role for Interleukin-18 in Human Natural Killer Cell Death"Arthritis Rheum. 44・4. 884-892 (2001)

[Publications] Kawakami A: "Role of HTLV-I Infection in the pathogenesis of Sjoren's syndrome and rheumatoid arthritis"Mod Rheumatol. 11・2. 87-90 (2001)

[Publications] Migita K: "FK506-Mediated T-Cell Apoptosis Induction"Transplant P. 33. 2292-2293 (2001)

[Publications] Yamasaki S: "Importance of NF-κB in rheumatoid synovial tissues : in situ NF-κB expression and in vitro study using cultured synovial cells"Ann Rheum Dis. 60・7. 678-684 (2001)

[Publications] Migita K: "Nitric oxide protects cultured rheumatoid synovial cells from Fas-induced apoptosis by inhibiting caspase-3"Immunology. 103. 362-367 (2001)

[Publications] Migita K: "Regulation of rheumatoid synoviocyte proliferation by endogenous p53 induction"Clin Exp Immunol. 126・2. 334-338 (2001)

[Publications] Urayama S: "New disease-modifying antirheumatic drug 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid(KE-298) selectively augments activation-induced T cell death"J Lab Clin Med. 138. 11-17 (2001)

[Publications] 江口勝美: "特集 リウマチ性疾患とウイルスHTLV-I感染とリウマチ性疾患"リウマチ科. 27・3. 238-246 (2002)

[Publications] 川上 純: "HTLV-I感染によるシェーグレン症候群・慢性関節リウマチの発症機序"臨床リウマチ. 13. 11-17 (2001)

[Publications] 江口勝美: "炎症におけるHTLV-I感染の役割"血液・免疫・腫瘍. 6・2. 61-71 (2001)

[Publications] Migita K: "Mechanistic Difference of Cornerstone Immunosuppressants"Fujisawa. 6 (2001)

江口勝美長崎大学, 大学院・医歯薬学総合研究科, 教授 (30128160)

[Publications] 江口勝美: "特集リウマチ性疾患とウイルスHTLV-I感染とリウマチ性疾患"リウマチ科. 27・3. 238-246 (2002)

[Publications] 川上純: "HTLV-I感染によるシェーグレン症候群・慢性関節リウマチの発症機序"臨床リウマチ. 13. 11-17 (2001)