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Abstract Background AATD is one of the most common inherited disorders in the World. However, it is generally accepted that AATD in North African populations is not a risk factor for lung and/or liver disease, based on a number of small studies. We therefore planned a screening study for detection of AATD in patients with OLD in a cohort of patients from Kairouan in central Tunisia. Methods: One hundred twenty patients with OLD (asthma, emphysema, COPD) were enrolled in the screening programme. Laboratory diagnosis for AATD was performed according to current diagnostic standards. Results We found that 6/120 OLD patients carried an AAT deficient allele, 1 PI*MZ, 1 PI*MPlowel, 3 PI*MMmalton, 1 PI*MMwurzburg. Conclusion this pilot study demonstrated that alleles related to deficiency of AAT are not absent in the Tunisian population, and that rare AATD variants prevailed over commonest PI*Z variant. These results would support a larger scale screening for AATD in Tunisia.

Abstract Background α1-antitrypsin and surfactant protein-A (SP-A) are major lung defense proteins. With the hypothesis that SP-A could bind α1-antitrypsin, we designed a series of in vitro experiments aimed at investigating the nature and consequences of such an interaction. Methods and results At an α1-antitrypsin:SP-A molar ratio of 1:1, the interaction resulted in a calcium-dependent decrease of 84.6% in the association rate constant of α1-antitrypsin for neutrophil elastase. The findings were similar when SP-A was coupled with the Z variant of α1-antitrypsin. The carbohydrate recognition domain of SP-A appeared to be a major determinant of the interaction, by recognizing α1-antitrypsin carbohydrate chains. However, binding of SP-A carbohydrate chains to the α1-antitrypsin amino acid backbone and interaction between carbohydrates of both proteins are also possible. Gel filtration chromatography and turnover per inactivation experiments indicated that one part of SP-A binds several molar parts of α1-antitrypsin. Conclusion We conclude that the binding of SP-A to α1-antitrypsin results in a decrease of the inhibition of neutrophil elastase. This interaction could have potential implications in the physiologic regulation of α1-antitrypsin activity, in the pathogenesis of pulmonary emphysema, and in the defense against infectious agents.

Background Knowledge of the role of the receptor for advanced glycation end products ( RAGE), particularly its soluble form (s RAGE), and of its advanced glycation end product ( AGE) ligand, N-(carboxymethyl)lysine adducts ( CML), is limited in chronic heart failure ( CHF) and in chronic obstructive pulmonary disease ( COPD). We evaluated whether the AGE/ RAGE system is activated in stable CHF and COPD, and whether plasma s RAGE and CML levels are affected by clinical and functional parameters. Materials and methods We measured plasma levels of s RAGE and CML using a sandwich enzyme-linked immunosorbent assay ( ELISA) in 143 subjects, aged ≥ 65 years, divided into five groups: 58 with CHF, 23 with COPD, 27 with CHF+ COPD and 35 controls (17 healthy smokers and 18 healthy nonsmokers). Individuals with diabetes were excluded from the study. Results Plasma levels of s RAGE and CML were higher in CHF patients than in controls [s RAGE: 0·48 (0·37-0·83) vs. 0·42 (0·29-0·52) ng/mL, P = 0·01; CML: 1·95 (1·58-2·38) vs. 1·68 (1·43-2·00) ng/mL, P = 0·01]. By contrast, s RAGE and CML were not different between both COPD and CHF+ COPD patients and controls ( P > 0·05). N-terminal pro-brain natriuretic peptide ( Nt-pro BNP) correlated with s RAGE, but not with CML, in the patient groups: CHF ( r = 0·43, P < 0·001), COPD ( r = 0·77, P < 0·0001) and CHF/ COPD ( r = 0·43, P = 0·003). Conclusions Plasma levels of s RAGE and CML are increased in CHF, but not in COPD patients. The robust association between NT-pro BNP, a diagnostic and prognostic marker in CHF, and sRAGE concentrations might suggest a possible BNP pathway of amplification of inflammation via the AGE/ RAGE system. [ABSTRACT FROM AUTHOR]

The laboratory diagnosis of alpha1-antitrypsin (AAT) deficiency (AATD) has evolved over the last 40 years since the first cases of the disorder were reported. It is currently performed in specialized centers, and it requires a combination of different biochemical methods: nephelometric AAT concentration, isoelectric focusing, genotyping, and sequencing. The availability of matrices such as the dried blood spot have facilitated the implementation of laboratory analyses for AATD, but they have also challenged laboratories to develop more reliable and reproducible techniques starting from dried blood. In this article, we describe the protocols we have optimized for AATD diagnosis from dried blood spot, in an attempt to hopefully provide useful information for physicians and scientists involved in this diagnostic line. We also describe the diagnostic flowchart for AATD detection that we have developed accordingly. [Copyright &y& Elsevier]

Background: α1-antitrypsin and surfactant protein-A (SP-A) are major lung defense proteins. With the hypothesis that SP-A could bind α1-antitrypsin, we designed a series of in vitro experiments aimed at investigating the nature and consequences of such an interaction. Methods and results: At an α1-antitrypsin:SP-A molar ratio of 1:1, the interaction resulted in a calcium-dependent decrease of 84.6% in the association rate constant of α1-antitrypsin for neutrophil elastase. The findings were similar when SP-A was coupled with the Z variant of α1-antitrypsin. The carbohydrate recognition domain of SP-A appeared to be a major determinant of the interaction, by recognizing α1-antitrypsin carbohydrate chains. However, binding of SP-A carbohydrate chains to the α1-antitrypsin amino acid backbone and interaction between carbohydrates of both proteins are also possible. Gel filtration chromatography and turnover per inactivation experiments indicated that one part of SP-A binds several molar parts of α1-antitrypsin. Conclusion: We conclude that the binding of SP-A to α1-antitrypsin results in a decrease of the inhibition of neutrophil elastase. This interaction could have potential implications in the physiologic regulation of α1-antitrypsin activity, in the pathogenesis of pulmonary emphysema, and in the defense against infectious agents. [ABSTRACT FROM AUTHOR]