Source: Annual Congress 2012 - Lung transplantation: studies in candidates and recipients
Disease area: Airway diseases

Abstract

Z antitrypsin (Z-AT) polymerises in the liver and is associated with early onset emphysema. Z-AT polymers are inactive as antiproteinases. We studied patients with and without Z-AT deficiency who had had a lung transplant for emphysema, to examine the relationship between oxidized-polymers (Ox-pZ-AT) and infection/inflammation. BALF was obtained at scheduled surveillance, and as indicated for infection/rejection and airway injury and, assessed by ELISA and immunoblot using a mAb (3F4) to oxidized AT. BALF cell pellets were lysed and HLE activity was used as a measure of PMN count. 16 patients post-transplant were evaluated, 6 Z-AT (15 samples); 9 infective tracheobronchitis, 3 airway stenosis, 1 reflux, 2 normal, and 10 M-AT (20 samples); 7 infective tracheobronchitis, 8 rejection, 5 normal. The Z-AT group with infection had higher Ox-pZ-AT; 386±85ng/ml mean(SEM), p<0.001 (compared with non-infected Z-AT group, 100±46ng/ml) and confirmed by immunoblot. The Z-AT group had higher free HLE than M-AT, 139(226-102)ng/ml vs. 74(105-46), (Z vs. M), p<0.001. Free HLE in Z-AT was correlated with Ox-pZ-AT levels; R²=0.89. HLE assay of lysed neutrophils showed that the Z-AT group had a higher total PMN count than M-AT; 81±19ng/ml vs. 39±15, p=0.03; infected Z-AT (54±9ng/ml) vs. infected M-AT (31±8), p=0.03. Ox-pZ-AT present in BALF of Z-AT transplanted individuals are associated with excess PMN and, closely correlated with free HLE. Ox-pZ-AT production results in further reduction of the anti-proteinase and anti-inflammatory protection in the lung and leads to PMN influx. This may predispose Z-AT individuals to exaggerated lung destruction and a worse outcome after lung transplantation.

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Citations should be made in the following way:
S. Alam, K. Santhanakrishnan, J. Parmar, R. Mahadeva (Cambridge, United Kingdom). Oxidized-polymers of Z-AT are associated with exaggerated pulmonary inflammation post lung transplantation. Eur Respir J 2012; 40: Suppl. 56, 1491

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