Anti-SERPINA1 monoclonal antibody

Background: Alpha-1 antitrypsin deficiency (AATD) results from mutations in the SERPINA1 gene and classically presents with early-onset emphysema and liver disease. The most common mutation presenting with clinical evidence is the Z mutation, while the S mutation is associated with a milder plasma deficiency. AATD is an under-diagnosed condition and the World Health Organisation recommends targeted detection programmes for AATD in patients with chronic obstructive pulmonary disease (COPD), non-responsive asthma, cryptogenic liver disease and first degree relatives of known AATD patients. Methods: We present data from the first 3,000 individuals screened following ATS/ERS guidelines as part of the Irish National Targeted Detection Programme (INTDP). We also investigated a DNA collection of 1,100 individuals randomly sampled from the general population. Serum and DNA was collected from both groups and mutations in the SERPINA1 gene detected by phenotyping or genotyping. Results: The Irish National Targeted Detection Programme identified 42 ZZ, 44 SZ, 14 SS, 430 MZ, 263 MS, 20 IX and 2 rare mutations. Analysis of 1,100 randomly selected individuals identified 113 MS, 46 MZ, 2 SS and 2 SZ genotypes. Conclusion: Our findings demonstrate that AATD in Ireland is more prevalent than previously estimated with Z and S allele frequencies among the highest in the world. Furthermore, our targeted detection programme enriched the population of those carrying the Z but not the S allele, suggesting the Z allele is more important in the pathogenesis of those conditions targeted by the detection programme.

Alpha-1 antitrypsin (AAT) is an acute phase protein produced in hepatocytes. Its deficiency affects the lungs and liver. A case-control study was carried out to determine the prevalence of 2 common deficiency alleles, PIS and PIZ, for alpha-1 antitrypsin deficiency (AATD) in both healthy and chronic obstructive pulmmonary disease (COPD)-affected Saudi populations and to clarify the importance of genetic tests in the screening of people at risk for COPD.One thousand blood samples from healthy individuals and 1000 from COPD-affected Saudi individuals were genotyped for the above-mentioned alleles, using real-time polymerase chain reaction (PCR), with the exclusion of any other nationalities. Data were analyzed by determining the allele and genotype frequencies through gene counting and its confidence intervals. The allele frequencies, derived by the Hardy-Weinberg equilibrium method, were analyzed by Pearson Chi-squared tests. The confidence intervals for genotype frequencies were calculated using exploratory software for confidence intervals.Of the 1000 COPD patients included in our study, the prevalence of PIS and PIZ was 21.8% and 7.7%, respectively, while within the 1000 normal samples, these alleles occurred in 8.9% of patients for PIS and 1.6% for PIZ. The AAT deficiency genotype frequencies (PIZZ, PISS, and PISZ) were 6.5 per 1000 and 87 per 1000 for normal and COPD-affected Saudi individuals.Our results indicated a high prevalence of AATD alleles in the normal Saudi population and an association between AAT deficiency and pulmonary disease development. Additionally, our research confirms the importance of genetic screening to achieve early and accurate diagnosis of AATD.