Immune activation in alpha-1 antitrypsin deficiency related and usual chronic obstructive pulmonary disease

Hampson, Judith Anne (2018). Immune activation in alpha-1 antitrypsin deficiency related and usual chronic obstructive pulmonary disease. University of Birmingham. M.D.

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Abstract

A polyclonal increase in free light chains (FLCs) has been observed in a number of chronic inflammatory and autoimmune conditions and may be considered a biomarker of adaptive immune activation. The aim of this study was to examine whether FLCs could be a useful clinical biomarker in alpha-1 antitrypsin deficiency (A1ATD) and chronic obstructive pulmonary disease (COPD).

Combined (\(\kappa\) & \(\lambda\)) FLCs (cFLCs) were measured in patients with AlATD and usual COPD in the stable state and assessed for association with clinical phenotype, disease severity, bacterial colonisation and mortality. The relationship of FLCs to total immunoglobulin levels was also examined in the COPD cohort. In addition, FLCs were measured in a small cohort of patients with bronchiectasis to further examine the relationship to bacterial colonisation.

Circulating cFLCs were static in the stable state in both A1ATD and usual COPD. Levels were significantly higher in patients with chronic bronchitis and airway bacterial colonisation in AlATD. After adjusting for renal function and age the relationship between cFLCs and lung function was weak, however cFLC levels greater than normal significantly associated with mortality in both COPD cohorts. In conclusion, cFLCs may be a promising biomarker for risk stratification in AlATD and COPD.

Type of Work:

Thesis (Higher Doctorates > M.D.)

Award Type:

Higher Doctorates > M.D.

Supervisor(s):