Gross W L, Csernok E, Flesch B K
Medical University in Lübeck, Department of Clinical Rheumatology, and Rhemaklinik Bad Bramstedt, Germany.
J Autoimmun. 1993 Apr;6(2):171-84. doi: 10.1006/jaut.1993.1015.
Wegener's autoantigen (WA), a 29 kD multifunctional protein, is the principal target antigen of autoantibodies associated with Wegener's granulomatosis (WG). WA was first identified as proteinase 3 (PR3), which is now known to be identical with myeloblastin and AGP7. Like other lysosomal proteins, WA/PR3 displays enzymatic activity, differentiation factor activity for myeloid precursor cells, and antimicrobial functions. Neutrophilic polymorphonuclear leukocytes (PMN) and a subpopulation of monocytes contain high levels of WA/PR3 in their myeloperoxidase-positive granules. The autoantibodies from WG sera produce a finely granular, centrally accentuated fluorescence pattern on PMN and monocytes and have been designated 'classic' pattern antineutrophil cytoplasmic autoantibodies (cANCA). However, PMN/monocyte activation (in vitro/ex vivo) is associated with the translocation of WA/PR3 on the cytoplasm membrane. WA/PR3 is accessible to the WG-associated autoantibody: cANCA stimulate cytokine-preactivated PMN to produce oxygen radicals and to degranulate. Furthermore, cANCA interfere with the biological functions of WA/PR3 (e.g. inhibition of elastinolytic activity). Hence, cANCA represents not only the best seromarker for WG so far available, but several lines of evidence indicate that the autoantibodies against WA/PR3 play a major role in the pathogenesis of this enigmatic disease.
韦格纳自身抗原（WA）是一种29kD的多功能蛋白，是与韦格纳肉芽肿病（WG）相关的自身抗体的主要靶抗原。WA最初被鉴定为蛋白酶3（PR3），现在已知它与成髓细胞素和AGP7相同。与其他溶酶体蛋白一样，WA/PR3具有酶活性、对髓系前体细胞的分化因子活性和抗菌功能。嗜中性多形核白细胞（PMN）和单核细胞亚群在其髓过氧化物酶阳性颗粒中含有高水平的WA/PR3。来自WG血清的自身抗体在PMN和单核细胞上产生细颗粒状、中央增强的荧光模式，被称为“经典”模式抗中性粒细胞胞浆自身抗体（cANCA）。然而，PMN/单核细胞激活（体外/体内）与WA/PR3在细胞质膜上的易位有关。WA/PR3可被与WG相关的自身抗体识别：cANCA刺激细胞因子预激活的PMN产生氧自由基并脱颗粒。此外，cANCA干扰WA/PR3的生物学功能（如抑制弹性蛋白酶活性）。因此，cANCA不仅是目前可用的WG的最佳血清标志物，而且有几条证据表明针对WA/PR3的自身抗体在这种神秘疾病的发病机制中起主要作用。
