Systemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn's disease differentially activate the innate immune response
Systemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn's disease differentially activate the innate immune response
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DOI：
10.1136/gut.53.1.91
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发表时间：
2004-01-01
期刊：
影响因子：
24.5
通讯作者：
Macfarlane, GT
中科院分区：
文献类型：
--
作者：
Furrie, E;Macfarlane, S;Macfarlane, GT
背景和目的：溃疡性结肠炎 (UC) 的粘膜充满了产生抗体的血浆 B 细胞和多形核白细胞 (PMN)。这种效应细胞组合需要交联抗原，通过其 Fc 受体引发抗体驱动的中性粒细胞炎症反应。激活的刺激被认为是定植于肠粘膜的共生细菌。本研究的目的是比较 UC 患者直肠粘膜上的主要可培养细菌群，并确定针对这些细菌的特异性抗体是否可以通过调理作用激活浸润性中性粒细胞。这将为这种慢性炎症状况提供解释。方法：使用化学分类学技术对定植直肠组织的细菌进行表征。在 UC 和克罗恩病 (CD) 患者以及健康对照中，测量了针对这些生物体的总抗原和表面抗原的全身抗体反应。还针对一系列粘膜分离株研究了 PMN 中呼吸爆发的抗体增强作用。结果：在 UC 活检中的一些细菌群体中观察到明显差异，这通常反映在针对这些生物体的抗体反应中。 UC患者对表面抗原有较高的IgG反应，主要是IgG1，而CD患者的反应主要是IgG2。来自 UC 患者的抗体极大地增强了 PMN 中的呼吸爆发，以响应个别细菌种类。结论：粘膜细菌的变化，以及从内部到主要 IgG1 类型的表面抗原/抗体反应性的转变，导致 PMN 中呼吸爆发的更大调理作用，为维持 UC 中的炎症状态提供了机制。
Background and aims: The mucosa in ulcerative colitis ( UC) is replete with antibody producing plasma B cells and polymorphonuclear leucocytes ( PMN). This combination of effector cells requires a crosslinking antigen to evoke an antibody driven PMN inflammatory response via their Fc receptors. The stimulus for activation is thought to be commensal bacteria colonising the gut mucosa. The aim of this investigation was to compare the principal culturable bacterial populations on the rectal mucosa of UC patients, and to determine whether specific antibodies towards these bacteria can activate infiltrating PMN through opsonisation. This would provide an explanation for this chronic inflammatory condition.Methods: Bacteria colonising rectal tissue were characterised using chemotaxonomic techniques. Systemic antibody responses were measured against total antigens and surface antigens of these organisms in UC and Crohn's disease ( CD) patients, together with healthy controls. Antibody enhancement of the respiratory burst in PMN was also investigated, against a range of mucosal isolates.Results: Distinct differences were observed in some bacterial populations in UC biopsies, which were generally reflected in antibody responses towards these organisms. UC patients had higher IgG responses to surface antigens, primarily IgG1, whereas the response in CD was mainly IgG2. Antibodies from UC patients greatly enhanced the respiratory burst in PMN, in response to individual bacterial species.Conclusions: Changes in mucosal bacteria, and a switch from internal to surface antigen/ antibody reactivity of a predominantly IgG1 type, leads to greater opsonisation of the respiratory burst in PMN, providing a mechanism for maintaining the inflammatory state in UC.