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抗中性粒细胞胞浆抗体(ANCA)患者中针对特定次要靶抗原的抗体

Antibodies to selected minor target antigens in patients with anti-neutrophil cytoplasmic antibodies (ANCA).

作者信息

Talor M V, Stone J H, Stebbing J, Barin J, Rose N R, Burek C L

机构信息

Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

出版信息

Clin Exp Immunol. 2007 Oct;150(1):42-8. doi: 10.1111/j.1365-2249.2007.03453.x. Epub 2007 Jul 5.

Abstract

In patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, indirect immunofluorescence (IF) distinguishes between cytoplasmic (C-ANCA) and perinuclear (P-ANCA) neutrophil staining patterns. In patients with primary systemic vasculitis such as Wegener's granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome, these IF staining patterns correspond broadly with antibodies to the two major antigens: the C-ANCA pattern is associated generally with antibodies to serine protease 3 (PR3) and the P-ANCA pattern with antibodies to myeloperoxidase (MPO). However, some sera positive for ANCA by IF are negative for anti-PR3 and anti-MPO antibodies, suggesting the presence of antibodies to minor antigens of PMN granules. We tested sera from a previously well-defined clinical cohort of patients for antibodies to four possible minor antigens: bactericidal permeability increasing protein, elastase, cathepsin G and lactoferrin. IF-positive (+) sera had significantly higher antibody frequencies to the minor antigens than did the IF-negative (-) sera (P < 0.01). Patients with IF(+) PR3(-)MPO(-) sera showed the most varied reactivity to the minor antigens. Among the IF(+) groups, the IF(+) PR3(+)/MPO(-) sera showed the lowest reactivity to the minor antigens. Patients with well-defined ANCA specificities, e.g. the PR3-ANCA response associated with Wegener's granulomatosis, are less likely than are other patient subsets to have antibodies to minor antigen targets. Autoantibodies to these minor antigens contribute to the overall pattern of ANCA identified by IF and help to explain why the correlation between IF and enzyme immunoassays show discrepancies. While the pathophysiological significance of antibodies to minor target antigens needs further evaluation, they may be markers of inflammation associated with disease processes.

摘要

在抗中性粒细胞胞浆抗体(ANCA)相关性血管炎患者中,间接免疫荧光法(IF)可区分中性粒细胞的胞浆(C-ANCA)和核周(P-ANCA)染色模式。在原发性系统性血管炎患者中,如韦格纳肉芽肿、显微镜下多血管炎和变应性肉芽肿性血管炎,这些IF染色模式与针对两种主要抗原的抗体大致对应:C-ANCA模式通常与抗丝氨酸蛋白酶3(PR3)抗体相关,P-ANCA模式与抗髓过氧化物酶(MPO)抗体相关。然而,一些通过IF检测ANCA呈阳性的血清,其抗PR3和抗MPO抗体呈阴性,提示存在针对PMN颗粒次要抗原的抗体。我们检测了来自一个先前明确界定的临床队列患者的血清,以检测针对四种可能的次要抗原的抗体:杀菌通透性增加蛋白、弹性蛋白酶、组织蛋白酶G和乳铁蛋白。IF阳性(+)血清对次要抗原的抗体频率显著高于IF阴性(-)血清(P<0.01)。IF(+)PR3(-)MPO(-)血清的患者对次要抗原的反应性最为多样。在IF(+)组中,IF(+)PR3(+)/MPO(-)血清对次要抗原的反应性最低。具有明确ANCA特异性的患者,例如与韦格纳肉芽肿相关的PR3-ANCA反应,比其他患者亚组产生针对次要抗原靶点抗体的可能性更小。针对这些次要抗原的自身抗体有助于IF所识别的ANCA总体模式的形成,并有助于解释为什么IF与酶免疫测定之间的相关性存在差异。虽然针对次要靶抗原的抗体的病理生理意义需要进一步评估,但它们可能是与疾病过程相关的炎症标志物。

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