Daffa N I, Tighe P J, Corne J M, Fairclough L C, Todd I
School of Life Sciences, University of Nottingham, Nottingham, UK; Medical Microbiology Department, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
Clin Exp Immunol. 2015 Apr;180(1):155-63. doi: 10.1111/cei.12565.
Autoimmunity may contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD). Studies have identified disease-specific autoantibodies (DSAAbs) in COPD patients, but natural autoantibodies (NAAbs) may also play a role. Previous studies have concentrated on circulating autoantibodies, but lung-associated autoantibodies may be most important. Our aim was to investigate NAAbs and DSAAbs in the circulation and lungs of COPD smoking (CS) patients compared to smokers (S) without airway obstruction and subjects who have never smoked (NS). Immunoglobulin (Ig)G antibodies that bind to lung tissue components were significantly lower in the circulation of CS patients than NS (with intermediate levels in S), as detected by enzyme-linked immunosorbent assay (ELISA). The levels of antibodies to collagen-1 (the major lung collagen) detected by ELISA were also reduced significantly in CS patients' sera compared to NS. The detection of these antibodies in NS subjects indicates that they are NAAbs. The occurrence of DSAAbs in some CS patients and S subjects was indicated by high levels of serum IgG antibodies to cytokeratin-18 and collagen-5; furthermore, antibodies to collagen-5 eluted from homogenized lung tissue exposed to low pH (0·1 M glycine, pH 2·8) were raised significantly in CS compared to S and NS. Thus, this study supports a role in COPD for both NAAbs and DSAAbs.
自身免疫可能在慢性阻塞性肺疾病（COPD）的发病机制中起作用。研究已在COPD患者中鉴定出疾病特异性自身抗体（DSAAbs），但天然自身抗体（NAAbs）可能也发挥作用。以往研究主要集中在循环自身抗体上，但与肺相关的自身抗体可能最为重要。我们的目的是调查与无气道阻塞的吸烟者（S）和从不吸烟的受试者（NS）相比，COPD吸烟（CS）患者循环和肺中的NAAbs和DSAAbs。通过酶联免疫吸附测定（ELISA）检测发现，与NS相比，CS患者循环中与肺组织成分结合的免疫球蛋白（Ig）G抗体显著降低（S的水平处于中间）。与NS相比，ELISA检测的CS患者血清中针对胶原蛋白-1（主要的肺胶原蛋白）的抗体水平也显著降低。在NS受试者中检测到这些抗体表明它们是NAAbs。一些CS患者和S受试者中DSAAbs的出现表现为血清中针对细胞角蛋白-18和胶原蛋白-5的IgG抗体水平较高；此外，与S和NS相比，从暴露于低pH（0·1 M甘氨酸，pH 2·8）的匀浆肺组织中洗脱的针对胶原蛋白-5的抗体在CS中显著升高。因此，本研究支持NAAbs和DSAAbs在COPD中均起作用。
