{
  "abstract": "Alpha-1 antitrypsin deficiency (AATD) predisposes individuals to early-onset chronic obstructive pulmonary disease (COPD), yet the molecular differences that distinguish AATD patients who develop COPD from those who do not remain poorly defined. Our aim was to understand protein-level changes which may uncover mechanisms contributing to disease progression in this genetically susceptible population. Protein expression was measured in the serum of subjects with AATD in our Alpha-1 Registry, using the SomaScan® 7 k platform (SomaLogic). Analysis was limited to those with the PiZZ genotype (associated with most severe deficiency) and those without concurrent bronchiectasis. Comparative proteomic analysis was performed between n=98 subjects with a clinical diagnosis of COPD and n=51 without COPD. Log2fold change was calculated, alongside p value and false discovery rate (FDR).The top five upregulated proteins in COPD patients were AGER, CILP2, IGDCC4, IGFALS, and tetranectin, while the top five downregulated proteins were PLAT, cathepsin D, TAGLN, LILRA5, and complement component C7. These findings highlight distinct dysregulation in pathways related to chronic inflammation (e.g., AGER), extracellular matrix remodelling (CILP2, tetranectin), and immune regulation (LILRA5, C7). Notably, the downregulation of PLAT and cathepsin D suggests a disruption in fibrinolysis and lysosomal function, potentially impairing normal tissue turnover and immune clearance. Upregulation of AGER further supports a role for oxidative stress and epithelial injury in COPD pathogenesis within the AATD cohort.Our study identified key protein expression differences between AATD individuals with and without COPD, implicating altered fibrinolytic balance, immune signalling, and inflammatory responses in disease development. These protein-level insights may inform future biomarker development and therapeutic strategies tailored to AATD-related COPD.",
  "authors": [
    {
      "affiliations": [
        "University of Birmingham, Birmingham, UK"
      ],
      "name": "DA Spittle"
    },
    {
      "affiliations": [
        "University of Birmingham, Birmingham, UK"
      ],
      "name": "J De Soyza"
    },
    {
      "affiliations": [
        "University of Birmingham, Birmingham, UK"
      ],
      "name": "A Pye"
    },
    {
      "affiliations": [
        "University of Birmingham, Birmingham, UK"
      ],
      "name": "AM Turner"
    }
  ],
  "title": "S119 Dysregulated inflammatory, immune and fibrinolytic pathways are associated with COPD in subjects with alpha-1 antitrypsin deficiency",
  "uid": "130374e9-7727-5d66-9552-7638bb645a1c"
}