臨床検査55巻11号

2011年10月発行

特集 ここまでわかった自己免疫疾患 各論 3．膠原病と類縁疾患

5) 血管炎症候群

著者： 尾崎承一¹

所属機関： ¹聖マリアンナ医科大学リウマチ・膠原病・アレルギー内科

ページ範囲：P.1164 - P.1171

血管炎とは血管壁の炎症をきたす病態の総称である．その多くは多因子疾患であり，発症には遺伝因子と環境因子が関与する．両者の相互作用の結果，一部の血管炎では自己免疫現象を介して血管の障害に向かうと考えられている．自己免疫現象は細胞性免疫および液性免疫のそれぞれで起きることが知られており，前者では肉芽腫形成性の自己反応性T細胞，後者の自己抗体には抗糸球体基底膜抗体，抗好中球細胞質抗体，抗内皮細胞抗体などがある．血管炎症候群の発症には，自己寛容の破綻により自己反応性T細胞や自己抗体が出現する過程が重要である．

参考文献

1) Seko Y, Minota S, Kawasaki A, et al : Perforin-secreting killer cell infiltration and expression of a 65-kD heat-shock protein in aortic tissue of patients with Takayasu's arteritis. J Clin Invest　93：750-758，1994

2) Brack A, Geisler A, Martinez-Taboada VM, et al : Giant cell vasculitis is a T cell-dependent disease. Mol Med　3：530-543，1997

3) Ma-Krupa W, Jeon MS, Spoerl S, et al : Activation of arterial wall dendritic cells and breakdown of self-tolerance in giant cell arteritis. J Exp Med　199：173-183，2004

4) Ly KH, Regent A, Tamby MC, et al : Pathogenesis of giant cell arteritis : More than just an inflammatory condition? Autoimmun Rev　9：635-645，2010

5) Weyand CM, Schönberger J, Oppitz U, et al : Distinct vascular lesions in giant cell arteritis share identical T cell clonotypes. J Exp Med　179：951-960，1994

6) Gillot JM, Masy E, Davril M, et al : Elastase derived elastin peptides : putative autoimmune targets in giant cell arteritis. J Rheumatol　24：677-682，1997

7) Borza DB, Netzer KO, Leinonen A, et al : The goodpasture autoantigen. Identification of multiple cryptic epitopes on the NC1 domain of the α3 (IV) collagen chain. J Biol Chem　275：6030-6037，2000

8) Cairns LS, Phelps RG, Bowie L, et al : The fine specificity and cytokine profile of T-helper cells responsive to the α3 chain of type IV collagen in goodpasture's disease. J Am Soc Nephrol　14：2801-2812，2003

9) Zhang Y, Su SC, Hecox DB, et al : Central tolerance regulates B cells reactive with Goodpasture antigen α3 (IV) NC1 collagen. J Immunol　181：6092-6100，2008

10) Wong D, Phelps RG, Turner AN : The Goodpasture antigen is expressed in the human thymus. Kidney Int　60：1777-1783，2001

11) Zou J, Henderson L, Thomas V, et al : Presentation of the Goodpasture autoantigen requires proteolytic unlocking steps that destroy prominent T cell epitopes. J Am Soc Nephrol　18：771-779，2007

lymphocytes of autoantigen-specific T-cell responses in Goodpasture's (anti-GBM) disease. Kidney Int　64：1685-1694，2003

13) Kain R, Matsui K, Exner M, et al : A novel class of autoantigens of anti-neutrophil cytoplasmic antibodies in necrotizing and crescentic glomerulonephritis : the lysosomal membrane glycoprotein h-lamp-2 in neutrophil granulocytes and a related membrane protein in glomerular endothelial cells. J Exp Med　181：585-597，1995

14) Kain R, Exner M, Brandes R, et al : Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nat Med　14：1088-1096，2008

15) Pendergraft WF 3rd, Preston GA, Shah RR, et al : Autoimmunity is triggered by cPR-3 (105-201), a protein complementary to human autoantigen proteinase-3．Nat Med　10：72-79，2004

16) Bautz DJ, Preston GA, Lionaki S, et al : Antibodies with dual reactivity to plasminogen and complementary PR3 in PR3-ANCA vasculitis. J Am Soc Nephrol　19：2421-2429，2008

17) Yang J, Bautz DJ, Lionaki S, et al : ANCA patients have T cells responsive to complementary PR-3 antigen. Kidney Int　74：1159-1169，2008

18) Sima D, Thiele B, Turowski A, et al : Anti-endothelial antibodies in Takayasu arteritis. Arthritis Rheum　37：441-443，1994

19) Kaneko K, Savage CO, Pottinger BE, et al : Antiendothelial cell antibodies can be cytotoxic to endothelial cells without cytokine pre-stimulation and correlate with ELISA antibody measurement in Kawasaki disease. Clin Exp Immunol　98：264-269，1994

20) Meroni PL, Khamashta MA, Youinou P, et al : Mosaic of anti-endothelial antibodies. Review of the first international workshop on anti-endothelial antibodies : clinical and pathological significance Milan, 9 November 1994．Lupus　4：95-99，1995

21) Karasawa R, Yudoh K, Ozaki S, et al : Anti-endothelial cell antibodies (AECA) in patients with systemic vasculitis : our research using proteomics. Expert Opin Biol Ther　11：77-87，2011

22) Karasawa R, Kurokawa MS, Yudoh K, et al. Peroxiredoxin 2 is a novel autoantigen for anti-endothelial cell antibodies in systemic vasculitis. Clin Exp Immunol　161：459-470，2010