Laboratory of Pneumology, Respiratory Medicine, University of Leuven, Onderwijs en Navorsing 1 bus 706, Herestraat 49, Leuven 3000, Belgium.
Thorax. 2012 Aug;67(8):694-700. doi: 10.1136/thoraxjnl-2011-200690. Epub 2012 Mar 22.
Antielastin autoimmunity has been hypothesised to drive disease progression in chronic obstructive pulmonary disease (COPD). The proposed mechanism is currently disputed by conflicting data. The authors aimed to explore antibody responses against elastin in a large and extensively characterised COPD population and to assess elastin-specific peripheral T-cell reactivity in a representative subgroup.
Antielastin antibodies were analysed with indirect ELISA on the plasma of 320 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease 1-4) and 143 smoking controls. In a second group of 40 patients with COPD and smoking controls, T-cell responses against extracellular matrix (elastin, collagen I and collagen V) were determined with enzyme-linked immunosorbent spot (EliSpot) (interferon γ (IFNγ) and interleukin-2) on peripheral blood mononuclear cells and compared with the responses of 11 never-smoking controls.
Antielastin antibody titres were not elevated in patients with COPD compared with smoking controls and even decreased significantly with increasing severity of COPD (p<0.001). Lower antielastin antibody titres were also found in a subgroup of patients with CT-proven emphysema. Elastin-specific INFγ-mediated T helper 1 responses could not be revealed in smoking subjects with and without COPD. Collagen I-mediated T-cell responses were also absent, which contrasted with a significant increased anticollagen V response in the smoking controls and patients with COPD compared with the never smokers (p=0.008). Collagen V-mediated T-cell responses could not discriminate between patients with COPD and smoking controls.
A systemic immune response against elastin could not be identified in patients with COPD. By contrast, collagen V-mediated autoimmunity was increased in the subgroup of smokers and may potentially contribute to the pathogenesis of COPD.
弹性蛋白自身免疫被认为是导致慢性阻塞性肺疾病（COPD）疾病进展的原因。目前，这一假说的机制存在相互矛盾的数据争议。本研究旨在探索大量特征明确的 COPD 患者人群中的抗弹性蛋白抗体反应，并在有代表性的亚组中评估弹性蛋白特异性外周 T 细胞反应。
采用间接酶联免疫吸附试验（ELISA）检测 320 例 COPD 患者（全球慢性阻塞性肺疾病倡议 1-4 期）和 143 例吸烟对照者的血浆中的抗弹性蛋白抗体。在第二组 40 例 COPD 患者和吸烟对照者中，采用酶联免疫斑点（ELISPOT）（干扰素 γ（IFNγ）和白细胞介素-2）测定细胞外基质（弹性蛋白、胶原蛋白 I 和胶原蛋白 V）的 T 细胞反应，并与 11 例从不吸烟的对照者进行比较。
与吸烟对照组相比，COPD 患者的抗弹性蛋白抗体滴度并未升高，甚至随着 COPD 严重程度的增加而显著降低（p<0.001）。在 CT 证实有肺气肿的亚组患者中也发现了较低的抗弹性蛋白抗体滴度。在有和没有 COPD 的吸烟人群中，均未发现弹性蛋白特异性 IFNγ介导的 Th1 反应。胶原蛋白 I 介导的 T 细胞反应也不存在，而在吸烟对照组和 COPD 患者中，与从不吸烟者相比，抗胶原蛋白 V 的反应明显增加（p=0.008）。胶原蛋白 V 介导的 T 细胞反应不能区分 COPD 患者和吸烟对照组。
在 COPD 患者中未发现针对弹性蛋白的系统性免疫反应。相比之下，在吸烟亚组中，胶原蛋白 V 介导的自身免疫反应增加，可能有助于 COPD 的发病机制。
