S71 Anti-microbial immune responses in obstructive lung diseases

Abstract

BackgroundPeople with chronic lung diseases, such as Bronchiectasis (BE) and smoking-induced Chronic Obstructive Pulmonary Disease (COPD), are susceptible to lung infections which can exacerbate their disease and can be life threatening. A relatively limited range of pathogens cause infections in these conditions and patients suffer repeated infections. It is unclear why such infections do not elicit protective adaptive immune responses. We wish to better understand immune responses against lung-infecting microbes in people with underlying lung disease since immune responses may be connected to disease pathology and also to protection from infection, and may provide a useful marker of colonisation.MethodsWe took peripheral blood samples from 114 BE and 47 COPD patients attending secondary care clinics, and 25 healthy controls, and extracted PBMC and serum. The patients were well-characterised clinically, including their history, aetiology, lung function and longitudinal microbial colonisation. T cell and antibody responses were measured against a panel of common lung-infecting microbial antigens (bacteria, fungi and viruses) using our in-house well-characterised assays (ELISA and ELIspot, respectively). These provided quantitative outputs of specific antibody titre and reactive gamma-interferon-secreting T cells per million PBMC, validated using positive controls. The sputum of patients was cultured, and microbial colonisation defined using prior definitions. Correlations between culture status and bacterial immune responses were analysed.ResultsThe predominant pathogens varied between BE and COPD as expected (percentages in Table 1). These included Pseudomonas, Haemophilus influenzae, Streptococcus pneumoniae and Moraxella spp. We found that specific IgG antibody responses correlated with bacterial sputum culture data for Pseudomonas (R = 0.61, p = 0.0001), but not with lung function nor number of exacerbations. In contrast, specific T cell responses did not correlate with microbiology.Abstract S71 Table 1 ConclusionsOur findings suggest that immune responses measured in the blood against potential lung pathogens contribute minimally to protection from infection or pathology. These tests may however help define colonisation status and could be used as surrogate markers of pathogens in the lung. The poor correlation between T cell responses may be a facet of the disease.