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Cellular studies in obstructive lung disease
S54 Polymers of Z α1-antitrypsin are associated with pulmonary infection post lung transplantation
  1. K Santhanakrishnan1,
  2. S Alam2,
  3. J Parmar1,
  4. R Mahadeva1
  1. 1Papworth Hospital, Cambridge, UK
  2. 2Department of Medicine, University of Cambridge, Cambridge, UK

Abstract

Z antitrypsin (Z-AT) polymerises in the liver and is associated with early onset emphysema. Polymers of Z-AT are not only inactivate as antiproteinases, but also act as a pro-inflammatory stimulus. We studied patients with emphysema post lung transplantation, with and without AT deficiency, to examine the relationship between polymers and the presence of infection and inflammation. Bronchoalveolar Lavage Fluid (BALF) was obtained at scheduled surveillance, and when clinically indicated to assess for infection, rejection and airway injury. BALF was assessed by ELISA and immunoblot using a monoclonal antibody to polymeric AT (ATZII). BALF cell pellets were lysed, and HLE activity was used as a measure of BALF neutrophil numbers. 16 patients post-transplant were evaluated, 6 Z-AT patients (15 samples); 9 infective tracheobronchitis, 3 airway stenosis, 1 reflux, 2 normal, and 10 M-AT patients (20 samples); 7 infective tracheobronchitis, 8 rejection, 5 normal. All samples apart from one in the Z-AT group contained polymers; median (IQR) 292 (430–40.2) ng/ml. In one patient BALF was initially negative for polymers, but subsequent samples were positive. Polymers were present in association bacterial infection, colonisation, airway injury and surveillance bronchoscopy of asymptomatic patients. Airway stenosis/inflammation and bacterial tracheobronchitis was associated with a higher amount of polymers (347.35 (SEM±57 ng/ml) than Z-AT with normal findings (142±101 ng/ml). Immunoblot confirmed the classical ladders of polymers in Z-AT group, but not in M-AT group. BALF of Z-AT group had a higher free HLE than M-AT; 139(226.5–102.75) ng/ml vs 74(105.25–46) ng/ml, respectively; p≤0.001. Free HLE in Z-AT was correlated with polymer concentrations in BALF; r2=0.63. Total neutrophil numbers were higher in Z-AT compared with M-AT; OD405, 0.57±0.07 vs 0.37±0.04, respectively; p=0.033. BALF neutrophil numbers were significantly higher in the infected Z-AT (0.54±0.1) vs infected M-AT (0.31±0.1), p=0.026. We have shown that polymers of Z-AT are present in BALF of transplanted individuals. Furthermore, this was associated with excess neutrophils, and closely correlated with free HLE. The production of polymers results in further reduction of the anti-proteinase and anti-inflammatory protection in the lung and leads to neutrophil influx. This may to predispose Z-AT individuals to exaggerated lung destruction and a worse outcome after lung transplantation.

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