PiSZ patients are less susceptible to cigarette smoke than PiZZ. The pattern of emphysema may be similar at diagnosis to usual COPD.

BackgroundCirculating free light chains (FLCs) can alter neutrophil migration, apoptosis and activation and may be a biomarker of autoimmune disease and adaptive immune system activation. These pathogenic roles could be relevant to lung disease in alpha 1 antitrypsin deficiency (A1ATD) and chronic obstructive pulmonary disease (COPD).MethodsTotal combined (c)FLCs were measured using the FreeLite® assay in 547 patients with A1ATD and 327 patients with usual COPD in the stable state, and assessed for association with clinical phenotype, disease severity, airway bacterial colonisation and mortality. Univariate and multivariate analyses were undertaken.ResultsCirculating cFLCs were static in the stable state when measured on 4 occasions in A1ATD and twice in usual COPD. Levels were inversely related to renal function (A1ATD and COPD p = <0.01), and higher in patients with chronic bronchitis (p = 0.019) and airway bacterial colonisation (p = 0.008). After adjusting for renal function and age the relationship between cFLCs and lung function was weak. Kaplan Meier curves showed that cFLC > normal (43.3 mg/L) significantly associated with mortality in both cohorts (A1ATD p = 0.001, COPD p = 0.013).ConclusionscFLCs may be a promising biomarker for risk stratification in A1ATD and COPD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0348-1) contains supplementary material, which is available to authorized users.

In this review, we explore potential novel roles of polyclonal free light chains (FLCs) as a biomarker of disease processes and predictor of mortality in different patient populations. In recent years, there have been many publications demonstrating raised polyclonal FLCs in several inflammatory and infective diseases. However, the potential utility of FLCs as a clinical biomarker remains an area of debate. We review the current evidence, and establish whether certain key criteria to fulfill the role of a useful biomarker have been satisfied. In addition, we also consider the potential role of FLCs in the pathophysiology of inflammatory disease and address the concepts of FLCs as both a therapeutic target and potential therapeutic agent.