S62Polyclonal free light chains: a potential biomarker for immune activation in alpha-1-antitrypsin deficiency (A1ATD) related chronic obstructive pulmonary disease

IntroductionA1ATD is a hereditary condition associated with the premature onset of chronic obstructive pulmonary disease (COPD). In COPD, the immune response within the lung is known to involve cells of both the innate and adaptive immune systems. However, the antigenic stimulus to the adaptive immune response remains unknown. Bacterial colonisation of the lower airways is one potential factor. Alternatively this could reflect an autoimmune component. The production of antibodies by B-cells is a key element of the adaptive immune system. An excess of free light chains (FLCs) are produced as a by-product of antibody synthesis. The recent discovery of high polyclonal FLC levels in a number of autoimmune and inflammatory conditions has led to the assessment of their value as a biomarker of adaptive immune activation. Our aim was to investigate the use of serum FLCs as a marker of immune activation, phenotypic variation and disease severity in COPD related to A1ATD.MethodsWe measured FLC levels in 294 patients with A1ATD using the Freelite registered serum FLC assay. We then compared combined (? & ?) FLC levels (cFLC) in different subgroups defined by the presence of chronic bronchitis, CT findings, smoking status, subsequent mortality and colonisation status. In addition we determined any correlation with lung function parameters in a cross sectional analysis.ResultsSignificantly higher cFLC levels were found to be associated with, subsequent mortality (p = 0.005), the presence of chronic bronchitis (p = 0.008) and chronic colonisation of the lower respiratory tract (p = 0.036) (Table 1). FLC levels are known to increase with age and reducing renal function. A partial correlation controlling for these factors revealed no relationship between cFLC levels and the severity of lung function impairment.Abstract S62 Table 1.Comparison of combined FLC (cFLC) concentrations in different sub groups (using Mann Whitney U test) Group 1Group 2P valueMortalityDead 11.2% median cFLC = 28.8 (IQR 16.2)Alive 88.8% median cFLC = 25.2 (IQR 10.1)0.005**EmphysemaYes 77.8% median cFLC = 25.2 (IQR 10.3)No 22.2% median cFLC = 26.8 (IQR 11.2)0.222BronchiectasisYes 31.9% median cFLC = 25.8 (IQR 10.4)No 68.1% median cFLC = 26.4 (IQR 10.5)0.446Chronic bronchitisYes 33.7% median cFLC = 27.8 (IQR 14.3)No 66.3% median cFLC = 25.0 (IQR 9.4)0.008**Current smokersYes 9.2% median cFLC = 25.4 (IQR 8.0)No 90.8% median cFLC = 26.1 (IQR 10.5)0.944Culture positive (1 stable sputum PPM >105 CFU/ml)Y