Perinuclear anti-neutrophil cytoplasmic antibodies are spontaneously produced by mucosal B cells of ulcerative colitis patients.
Perinuclear anti-neutrophil cytoplasmic antibodies are spontaneously produced by mucosal B cells of ulcerative colitis patients.
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DOI：
10.4049/jimmunol.155.6.3262
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发表时间：
1995-09
影响因子：
4.4
通讯作者：
S. Targan;C. Landers;L. Cobb;R. Macdermott;A. Vidrich
中科院分区：
文献类型：
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作者：
S. Targan;C. Landers;L. Cobb;R. Macdermott;A. Vidrich
大约60%的溃疡性结肠炎（UC）患者的血清中含有与中性粒细胞成分反应的Ig，这引起了这些抗中性粒细胞胞质抗体（ANCA）的起源问题。我们认为ANCA是粘膜疾病相关免疫反应的标志物，这一论断预测了UC患者固有层淋巴细胞（LPL）部分中存在产生ANCA的B细胞克隆。通过检查LPL ANCA表达的12天培养上清液来检验该假设。LPL分离自UC、克罗恩病（CD）和憩室炎患者的手术切除粘膜。正常粘膜取自事故受害者或结肠癌切除术的正常边缘。通过固定中性粒细胞ELISA测定上清液。通过酒精固定的中性粒细胞的间接免疫荧光染色评估表达ANCA的上清液的ANCA染色模式，如通过ELISA测定的。在UC LPL组分的70%培养上清液中发现ANCA。相反，CD和憩室炎/正常（非炎性肠病（IBD））LPL的上清液中仅约11%显示ANCA结合。用70%的ANCA表达UC LPL上清液获得核周（pANCA）染色模式，而ANCA表达CD和非IBD LPL上清液显示细胞质反应。PBL和肠系膜淋巴结淋巴细胞缺乏自发性pANCA产生，并且PBL的pANCA产生是不可诱导的。这些发现表明UC患者的粘膜病变中存在产生pANCA的B细胞克隆，并支持我们的假设，即pANCA的产生是UC特异性粘膜免疫应答的结果。
Approximately 60% of sera from ulcerative colitis (UC) patients contains Igs reactive with neutrophil components, raising the question of the origin of these anti-neutrophil cytoplasmic Abs (ANCA). Our assertion that ANCA is a marker for a mucosal disease-related immune response predicts the existence of ANCA producing B cell clones in the lamina propria lymphocyte (LPL) fraction of UC patients. This hypothesis was tested by examining 12-day culture supernatants of LPL ANCA expression. LPL were isolated from surgically removed mucosa from patients with UC, Crohn's disease (CD), and diverticulitis. Normal mucosa was obtained from accident victims or normal margins of colon cancer resections. Supernatants were assayed by a fixed neutrophil ELISA. The ANCA staining pattern of supernatants expressing ANCA, as determined by ELISA, was assessed by indirect immunofluorescent staining of alcohol-fixed neutrophils. ANCA was found in 70% of culture supernatants from UC LPL fractions. In contrast, only approximately 11% of supernatants from CD and diverticulitis/normal (noninflammatory bowel disease (IBD)) LPL displayed ANCA binding. A perinuclear (pANCA) staining pattern was obtained with 70% of ANCA-expressing UC LPL supernatants, whereas ANCA-expressing CD and non-IBD LPL supernatants displayed a cytoplasmic reaction. PBL and mesenteric lymph node lymphocytes lacked spontaneous pANCA production, and pANCA production from PBL was not inducible. These findings indicate the existence of pANCA-producing B cell clones in mucosal lesions of UC patients and support our hypothesis that pANCA production is a consequence of a mucosal immune response specific to UC.