LSC 2010 abstract : influence of mutations and COPD clinical features on SERPINA1 phenotypic expression
Published jointly by the Society for Clinical Respiratory Physiology and Munksgaard |
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2010 |
The aim of the study was to analyze and compare alpha-1 antitrypsin (AAT), CRP, TNF-α, TNFR1, TNFR2 concentration in COPD patients with different SERPINA1 variants. Methods: We analyzed 355 COPD patients with different SERPINA1 variants (PIMM, PIMZ, PISZ, PIZZ). The clinical diagnosis was confirmed by using GOLD spirometric criteria, SERPINA1 variants (AAT genotypes) were determined by means of isoelectic-focusing, alpha-1 antitrypsin concentration was evaluated by nephelometry, ELISA method was used to measure serum CRP, TNF-α, TNFR1, TNFR2 concentrations. Results: Comparing the PIZZ group against the remaining (PIMM, PIMZ and PISZ) genotypic groups, PIZZ showed: significant lower AAT serum concentration (0,4±0.34)(P< 0.001). In PIMM genotypic group AAT concentration positively correlated with inflammatory markers concentration: CRB (r=0.667, p< 0.01) and TNFR-1 (r=0.565, p< 0.01). We also found statistically significant negative correlation between AAT concentration and FEV1 % pred. in PIMM genotypic group (r = -0.511, P< 0.05). The net impact of AAT on COPD seems to be the result of context-dependent (i.e. SERPINA1 variant). On the one hand, elevated serum AAT can reflect a beneficial shift of the protease-antiprotease balance, the centre piece of the pathophysiological pathway mediating the effect of congenital AAT deficiency on COPD. On the other hand elevated serum AAT can also reflect ongoing inflammatory processes in the lung a hypothesized COPD risk factor. Conclusions: Our results demonstrated that in COPD pathogenesis a complex interrelationship among lung function, circulating AAT, systemic inflammatory status and SERPINA1 variation exists.