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S62 Polyclonal free light chains: a potential biomarker for immune activation in alpha-1-antitrypsin deficiency (A1ATD) related chronic obstructive pulmonary disease
  1. JA Brebner1,
  2. AM Turner2,
  3. RA Stockley1
  1. 1The ADAPT Project, Queen Elizabeth Hospital, Birmingham, United Kingdom
  2. 2Heart of England NHS Foundation Trust, Birmingham, United Kingdom

Abstract

Introduction A1ATD 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.

Methods We measured FLC levels in 294 patients with A1ATD using the Freelite® 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.

Results Significantly 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)

Conclusions These results suggest that A1ATD patients with chronic bronchitis and chronically colonised airways have a greater adaptive immune response compared to those without. Whether this response is driven directly by microorganisms residing in the airways, or through an autoimmune phenomenon remains to be elucidated. Whether the use of FLCs in sub cohorts could have an impact on the clinical management of patients with COPD is yet to be determined.

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