2001 Fiscal Year Annual Research Report

KIRおよび抗KIR自己抗体と膠原病における高γグロブリン血症との関連性の研究

Research Project

Project/Area Number	13670483
Research Institution	St. Marianna University School of Medicine
Principal Investigator	加藤智啓聖マリアンナ医科大学, 難病治療研究センター, 助教授 (80233807)
Keywords	自己抗体 / NK細胞 / Killer cell Immunoglobulin-like Receptor / 慢性関節リウマチ / 強皮症 / 全身性エリテマトーデス / シェーグレン症候群
Research Abstract	慢性関節リウマチ(RA)、強皮症(SSc)、全身性エリテマトーデス(SLE)、シェーグレン症候群(SjS)など全身性自己免疫疾患では高頻度に高γ-グロブリン血症が認められる。高γ-グロブリン血症は一般に非特異的B細胞活性化の結果と考えられているがその機序は明らかでない。一般にB細胞活性化にはT細胞の補助が必要であるが、NK細胞もT細胞とは独立してB細胞活性化の制御に関与している報告がある。我々はNK細胞上のとされるが、我々はNK細胞が細胞障害性を発揮する場合に標的細胞のMHCクラス1分子を認識し、自己非自己の区別を行う分子群であるKiller cell Immunoglobulin-like Receptor (KIR)のうち、p58.1、p58.2に対する自己抗体を検索した結果、RA患者の30%、SLE患者の23%、べーチェット病患者の27%にKIRに対する自己抗体を検出した。そして、その3疾患すべてにおいて抗KIR自己抗体陽性例の血清IgG値は抗KIR自己抗体陰性例のそれに比べ明らかに高いことが判明した(RA;1740+/-184 vs 1193+/-74,p=0.014,SLE;1900+/-185 vs 1280+/-108,p=0.009ベーチェット病;1489+/-74 vs 1116+/-66)。このことから、上述した非特異的B細胞活性化に対するNK細胞の関与において、KIRがなんらかの役割を担っている可能性が示された。現在、さらに、他のKIR分子に対する自己抗体の検出、KIR阻害によるB細胞活性化への影響を検討している。

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] Yu X et al.: "Anti-CO69 autoantibodiescrossreacc with low density lipoprotein receptor-related protein 2 in systemic autoimmune diseases"J Immunol.. 166. 1360-1369 (2001)
[Publications] Matsui T et al.: "Autoantibodies to CTLA-4enhance T cell proliferation"J Rheumatol.. 28. 220-221 (2001)
[Publications] Kurokawa M et al.: "Paired-cloning of the T cell receptor α and β genes from a single T cell without the establishment of a T cell clone"Clin. Exp. Immunol.. 123. 340-345 (2001)
[Publications] Matsui T et al.: "Detection of autoantibodies tokiller immunoglobulin-like receptors (KIRs) using recombinant KIRs in patients with systemis lupus erythematosus"Arthritis & Rheumatism. 44. 384-388 (2001)
[Publications] Nakamura H et al.: "Characterization of T cell receptor beta chains of accumulating T cells in chronic ongoing myocarditis demonstrated by heterotopic cardiac transplantation in mice"Jpn Circ. J.. 65. 106-110 (2001)
[Publications] Tsuruha J et al.: "Implication of cartilage intermediate layer protein in subsets of patients with osteoarthritis and rheumatoid arthritis"Arthritis & Rheumatism. 44. 838-845 (2001)
[Publications] Yuan GH et al.: "The role of CC chemokinesand their receptors CCR2 and CCR5 in osteoarthritis"Arthritis & Rheumatism. 44. 1056-1070 (2001)
[Publications] Pistillo MP et al.: "Patients with neoplastic and nonneoplastic hematologic diseases acquire CTLA-4 antibodies after blood transfusion"Transfusion. 41. 462-469 (2001)
[Publications] Hasunuma T et al.: "Apoptosis and arthritis : Pathogenesis and therapeutic intervention. In programmed cell death vol.11 advances in cell aging and gerontology"Elsevier (Amsterdam). 6. 81-100 (2001)
[Publications] Sakata M et al.: "Autoantibodies to osteopontin in patients with osteoarthritis and rheumatoid arthritis"J Rheumatol.. 28;7. 1492-1495 (2001)
[Publications] Tsumuki H et al.: "Infection of synoviocytes with HTLV-1 induces telomerase activity"Rheumatol Int.. Jul;20(5). 175-179 (2001)
[Publications] Masuko-Hongo K et al.: "Disappearance of Clonally Expanded T Cells After Allogenic Leukocyte Immunotherapy in peripheral Blood of Patients With Habitual Abortion"Hum. Immunol.. 63. 1111-1121 (2001)
[Publications] Masuko-Hongo K et al.: "Expression of Fas-associated death domain-like interleukin-1-converting enzyme (FLICE) inhibitory protein (FLIP) in human articular chondrocytes: possible contribution to the resistance to Fas-mediated death of in vitro cultured human articular chondrocytes"Rheumatol Int.. Nov;21(3). 112-121 (2001)

2001 Fiscal Year Annual Research Report

KIRおよび抗KIR自己抗体と膠原病における高γグロブリン血症との関連性の研究

Principal Investigator

加藤 智啓 聖マリアンナ医科大学, 難病治療研究センター, 助教授 (80233807)

Research Products

[Publications] Yu X et al.: "Anti-CO69 autoantibodiescrossreacc with low density lipoprotein receptor-related protein 2 in systemic autoimmune diseases"J Immunol.. 166. 1360-1369 (2001)

[Publications] Matsui T et al.: "Autoantibodies to CTLA-4enhance T cell proliferation"J Rheumatol.. 28. 220-221 (2001)

[Publications] Kurokawa M et al.: "Paired-cloning of the T cell receptor α and β genes from a single T cell without the establishment of a T cell clone"Clin. Exp. Immunol.. 123. 340-345 (2001)

[Publications] Matsui T et al.: "Detection of autoantibodies tokiller immunoglobulin-like receptors (KIRs) using recombinant KIRs in patients with systemis lupus erythematosus"Arthritis & Rheumatism. 44. 384-388 (2001)

[Publications] Nakamura H et al.: "Characterization of T cell receptor beta chains of accumulating T cells in chronic ongoing myocarditis demonstrated by heterotopic cardiac transplantation in mice"Jpn Circ. J.. 65. 106-110 (2001)

[Publications] Tsuruha J et al.: "Implication of cartilage intermediate layer protein in subsets of patients with osteoarthritis and rheumatoid arthritis"Arthritis & Rheumatism. 44. 838-845 (2001)

[Publications] Yuan GH et al.: "The role of CC chemokinesand their receptors CCR2 and CCR5 in osteoarthritis"Arthritis & Rheumatism. 44. 1056-1070 (2001)

[Publications] Pistillo MP et al.: "Patients with neoplastic and nonneoplastic hematologic diseases acquire CTLA-4 antibodies after blood transfusion"Transfusion. 41. 462-469 (2001)

[Publications] Hasunuma T et al.: "Apoptosis and arthritis : Pathogenesis and therapeutic intervention. In programmed cell death vol.11 advances in cell aging and gerontology"Elsevier (Amsterdam). 6. 81-100 (2001)

[Publications] Sakata M et al.: "Autoantibodies to osteopontin in patients with osteoarthritis and rheumatoid arthritis"J Rheumatol.. 28;7. 1492-1495 (2001)

[Publications] Tsumuki H et al.: "Infection of synoviocytes with HTLV-1 induces telomerase activity"Rheumatol Int.. Jul;20(5). 175-179 (2001)

[Publications] Masuko-Hongo K et al.: "Disappearance of Clonally Expanded T Cells After Allogenic Leukocyte Immunotherapy in peripheral Blood of Patients With Habitual Abortion"Hum. Immunol.. 63. 1111-1121 (2001)

加藤智啓聖マリアンナ医科大学, 難病治療研究センター, 助教授 (80233807)