Late Breaking Abstract - Severe alpha-1 antitrypsin deficiency is associated with increased expression of CD8+ T cell markers

<bold>Introduction:</bold> Alpha-1 antitrypsin (AAT) is an antiprotease and anti-inflammatory glycoprotein. AAT deficiency (AATD) is an autosomal co-dominant condition resulting in low plasma and lung AAT levels. The Z allele is the most common variant that encodes severe AAT deficiency. Consequently, Z homozygote individuals have increased risk of developing early onset COPD. CD8+ T cells, associated with inflammation and cytotoxic markers, are upregulated in COPD. However, the influence of the Z allele on CD8+ T cell markers is less well understood. <bold>Aims and objectives:</bold> To identify if severe AATD impacts the expression of CD8+ T cell markers. <bold>Methods:</bold> 20 MM and 20 ZZ individuals underwent time-matched phlebotomy and bronchoalveolar lavage (BAL). These were divided as healthy or COPD, as defined by clinical review, pulmonary function tests and CT of thorax. Multiplex ELISA was performed on matching plasma and BAL to quantify the expression of CD8+ markers (Human CD8/NK Panel V02,13-plex, 741187, Biolegend). <bold>Results:</bold> IL-4, TNFα, Granzyme A and Granzyme B were significantly upregulated in the plasma of ZZ individuals. In agreement with findings in plasma, IL-4 was significantly upregulated in the BAL of ZZ individuals. Healthy ZZ individuals had significantly higher expression of IL-2, IL-10, IL-6, TNFα and Granzyme B in plasma compared to healthy MM individuals. IL-4 was significantly upregulated in plasma of healthy ZZ compared to MM COPD individuals. <bold>Conclusions:</bold> The ZZ genotype is associated with increased expression of many CD8+ T cell markers, even in the absence of lung disease. This suggests a potential precursor to COPD and a novel biomarker in alpha-1 antitrypsin deficiency.