Immune Response to Haemophilus parainfluenzae in Patients with Chronic Obstructive Lung Disease

Haemophilus parainfluenzae is often isolated from the sputa of patients with chronic obstructive lung disease. We have investigated the immune response to this organism in patients with chronic bronchitis (n = 3) and bronchiectasis (n = 10) and in healthy controls (n = 9). Outer membrane proteins (OMPs) of H. parainfluenzae were purified for use in enzyme-linked immunosorbent and immunoblot assays. Whole-cell H. parainfluenzae preparations were used to adsorb antibodies from serum samples, which were subsequently immunoblot assayed to investigate the antibody response to surface-exposed epitopes. Levels of H. parainfluenzae-specific immunoglobulin G (IgG), but not IgA or IgM, were increased in the sera of patients with chronic obstructive lung disease compared to levels in control subjects. The species specificity of the antibody response was confirmed, although a degree of cross-reactivity with H. influenzae antigens was observed. IgA and IgG specific for OMPs of H. parainfluenzae were demonstrated to be present in the sputa and sera of five patients with chronic obstructive lung disease. Variation in the pattern and intensity of antigen recognition was observed among patients and among immunoglobulin classes. OMPs of approximately 36, 22, and 15 kDa were confirmed to possess epitopes exposed on the surface of intact H. parainfluenzae. We have demonstrated the presence of a species-specific systemic immune response to H. parainfluenzae in colonized patients. A specific antibody response was also observed in sputum, and the antigen specificity of these responses in patients with chronic obstructive lung disease was investigated for the first time. The presence of a specific immune response suggests that H. parainfluenzae may have a pathogenic role in patients with chronic obstructive lung disease.

副流感嗜血杆菌（Haemophilus parainfluenzae）常从慢性阻塞性肺疾病患者的痰液中分离得到。本研究针对慢性支气管炎患者（n=3）、支气管扩张患者（n=10）及健康对照者（n=9），开展了针对该菌的免疫应答相关研究。我们纯化了副流感嗜血杆菌的外膜蛋白（outer membrane proteins, OMPs），用于酶联免疫吸附试验与免疫印迹实验；同时采用全菌体副流感嗜血杆菌制剂吸附血清样本中的抗体，随后通过免疫印迹实验检测，以探究针对细菌表面暴露表位的抗体应答情况。与健康对照组相比，慢性阻塞性肺疾病患者血清中针对副流感嗜血杆菌的免疫球蛋白G（IgG）水平显著升高，而免疫球蛋白A（IgA）与免疫球蛋白M（IgM）水平无明显变化。本研究证实了该抗体应答的物种特异性，但同时观察到其与流感嗜血杆菌（H. influenzae）抗原存在一定程度的交叉反应性。研究人员在5例慢性阻塞性肺疾病患者的痰液与血清中，检测到针对副流感嗜血杆菌外膜蛋白的特异性IgA与IgG；不同患者之间以及不同免疫球蛋白类别之间，抗原识别的模式与强度均存在差异。经确认，分子量约36kDa、22kDa与15kDa的外膜蛋白带有暴露于完整副流感嗜血杆菌表面的表位。本研究证实，定植有副流感嗜血杆菌的慢性阻塞性肺疾病患者体内存在物种特异性的全身免疫应答；同时在痰液中也检测到了特异性抗体应答，本研究首次针对慢性阻塞性肺疾病患者的此类免疫应答展开了抗原特异性分析。特异性免疫应答的存在提示，副流感嗜血杆菌可能在慢性阻塞性肺疾病患者中发挥致病作用。