Diminished activity of circulating α1-antitrypsin is associated with pre-gestational isolated obesity.

OBJECTIVE: To examine possible correlation between α1-antitrypsin (AAT) levels and activity in patients with and without obesity, after excluding complications such as gestational diabetes mellitus (GDM), during pregnancy. STUDY DESIGN: A prospective case-control study was conducted. AAT levels were determined by standard human AAT ELISA according to the manufacturer's instructions. Elastase inhibition was determined by kinetic assay according to manufacturer recommendations. Assays were performed in duplicates and repeated twice for each sample in separate sessions. Patients with diabetes mellitus were excluded from the study. The Mann-Whitney U-test was performed in order to determine statistical differences between the groups, and AAT concentration and activity. RESULTS: During the study period, 43 patients were recruited: 21 with isolated obesity and 22 non-obese parturients (control group). According to ELISA, AAT concentrations were mildly lower in obese women compared with non-obese women (8.31 ± 0.28 mg/ml versus 9.5 ± 0.37 mg/ml, p = 0.0155). However, the elastase inhibitory capacity was markedly lower in obese versus non-obese parturients (mean 27.33 ± 2.08 % versus 43.73 ± 3.1%, p < 0.001). CONCLUSIONS: Isolated obesity in pregnancy is associated with lower activity of AAT. These findings correlate with the reduced concentration and activity of AAT found in patients with GDM. Accordingly, it might suggest an inflammatory axis shared by obesity and the development of insulin resistance.

Low levels of circulating alpha-1 antitrypsin are associated with spontaneous abortions.

OBJECTIVE: Alpha-1 antitrypsin (AAT), a circulating anti-inflammatory molecule, rises four- to sixfold during acute phase responses and during pregnancy. AAT deficiency is linked with various pregnancy complications. The aim of this study is to determine plasma concentrations and activity of AAT and serum cytokine levels in blood samples from women undergoing spontaneous abortions as compared with elective abortions. METHODS: A prospective case-control study consisted of patients with sporadic abortions (n = 15), recurrent spontaneous abortions (n = 14) and healthy pregnancies going through elective terminations (n = 11). Circulating AAT and cytokine levels were determined before dilatation and curettage. RESULTS: AAT levels were lower in both recurrent and sporadic spontaneous abortion groups compared with healthy pregnancies (1.421 ± 0.08, 1.569 ± 0.14 and 3.224 ± 0.45 mg/ml, respectively, p < 0.001). Reduced AAT levels correlated with elevated proinflammatory cytokines. CONCLUSIONS: AAT levels in patients with either sporadic or recurrent spontaneous abortions were lower than normal pregnancies, and were associated with an inflammatory profile. Future studies should examine larger cohort groups, effects of earlier time-points and the influence of antithrombotic therapy in such patients who are diagnosed with relatively low levels of circulating AAT, in an effort to improve pregnancy outcomes.

Lower circulation levels and activity of α-1 antitrypsin in pregnant women with severe preeclampsia.

OBJECTIVE: α-1 antitrypsin (AAT) is an anti-protease, anti-inflammatory and tissue-protective molecule. Normal circulating levels are <3.5 mg/dl and rise during pregnancy. Although AAT deficiency is associated with several pregnancy and placental disorders, little is known regarding AAT levels and preeclampsia. Since unopposed inflammation might contribute to preeclampsia, we studied whether preeclampsia is associated with lower than normal levels and activity of AAT. METHODS: In a prospective case-control study, we compared maternal serum AAT activity and levels between patients with severe preeclampsia (n = 23) and without preeclampsia (n = 18). RESULTS: AAT levels were 1.91 ± 0.08-fold lower in the preeclampsia group compared to healthy group (3.854 ± 0.26 vs. 7.397 ± 0.34 mg/ml; p < 0.001), and correlated with protease inhibitory capacity (46.56 ± 2.08% vs. 67.08 ± 1.74%; p < 0.001). CONCLUSIONS: Our findings show association between lower AAT levels and severe preeclampsia during pregnancy. Further studies are required to identify the mechanism behind the association, and the possibility of safe AAT augmentation for individuals with insufficient circulating AAT.

α1-antitrypsin insufficiency is a possible contributor to preterm premature rupture of membranes.

OBJECTIVE: α1-antitrypsin (AAT) is protective of tissue damage induced by enzymes of inflammatory cell source. Inflammatory cells are involved in preterm labor, preterm premature rupture of membrane (PPROM) and term premature rupture of membrane (PROM). The purpose of this research was to examine whether plasma concentration and activity of AAT differ between these manifestations. METHODS: In a prospective case control study, blood samples were assayed for AAT concentration and activity in 71 individuals. AAT concentration and activity were measured by standard methods. RESULTS: No significant differences were found between AAT levels (p = 0.497) and activity (p = 0.879) in preterm and term labor. AAT levels and activity in PPROM and PROM were not significantly different as well (p = 0.748 and p = 0.880, respectively). While 69 out of 71 patients displayed normal circulating levels of AAT, 2 PPROM patients out of 15 had abnormally low, previously undiagnosed,AAT concentrations, and had subsequently developed complications that were absent in the other groups. CONCLUSIONS: No statistically significant differences were demonstrated in the levels of AAT between patients with preterm and term labor, nor between preterm and term PROM. Yet, unexpectedly, patients that had marked AAT deficiency belonged exclusively to the PPROM group.