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

Madar, Tamar; Shahaf, Galit; Sheiner, Eyal; Brazg, Jared; Levinson, Justin; Salem, Shimrit Yaniv; Twina, Guy; Baron, Joel; Mazor, Moshe; Holcberg, Gershon; Lewis, Eli C.

doi:10.3109/14767058.2013.801955

Cited by 23 publications

(23 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The systemic rise in AAT levels during the third trimester of pregnancy highlights its significance as a tolerogenic agent. Pregnancy complications correlate with either non‐rising or non‐functional AAT levels, including premature rupture of membranes (suggestive of compromised tissue integrity) and spontaneous abortions (associated with immune intolerance) . Thus, while serum AAT may present as normal in these patients, it might not be the desired protective levels expected during the third trimester.…”

Section: Introductionmentioning

confidence: 99%

Acute-phase protein α1-anti-trypsin: diverting injurious innate and adaptive immune responses from non-authentic threats

Guttman

Baranovski

Schuster

et al. 2015

Clinical and Experimental Immunology

103

View full text Add to dashboard Cite

SummaryOne would assume that the anti-inflammatory activity of α1-anti-trypsin (AAT) is the result of inhibiting neutrophil enzymes. However, AAT exhibits tolerogenic activities that are difficult to explain by serine-protease inhibition or by reduced inflammatory parameters. Targets outside the serineprotease family have been identified, supporting the notion that elastase inhibition, the only functional factory release criteria for clinical-grade AAT, is over-emphasized. Non-obvious developments in the understanding of AAT biology disqualify it from being a straightforward anti-inflammatory agent: AAT does not block dendritic cell activities, nor does it promote viral and tumour susceptibilities, stunt B lymphocyte responses or render treated patients susceptible to infections; accordingly, outcomes of elevated AAT do not overlap those attained by immunosuppression. Aside from the acutephase response, AAT rises during the third trimester of pregnancy and also in advanced age. At the molecular level, AAT docks onto cholesterol-rich lipid-rafts and circulating lipid particles, directly binds interleukin (IL)-8, ADAM metallopeptidase domain 17 (ADAM17) and danger-associated molecular pattern (DAMP) molecules, and its activity is lost to smoke, high glucose levels and bacterial proteases, introducing a novel entity -'relative AAT deficiency'. Unlike immunosuppression, AAT appears to help the immune system to distinguish between desired responses against authentic threats, and unwanted responses fuelled by a positive feedback loop perpetuated by, and at the expense of, inflamed injured innocent bystander cells. With a remarkable clinical safety record, AAT treatment is currently tested in clinical trials for its potential benefit in a variety of categorically distinct pathologies that share at least one common driving force: cell injury.

show abstract

Section: Introductionmentioning

confidence: 99%

Acute-phase protein α1-anti-trypsin: diverting injurious innate and adaptive immune responses from non-authentic threats

Guttman

Baranovski

Schuster

et al. 2015

Clinical and Experimental Immunology

103

View full text Add to dashboard Cite

show abstract

“…14 Furthermore, AAT may play a role in fertility regulation, pregnancy loss and other obstetric pathologies. [15][16][17][18][19][20][21][22] Finally, there is data from maternal serum protein profiling showing that alpha-1-antitrypsin is among the markers for non-invasive prenatal diagnoses of trisomy 21, 18 and 13. 23…”

Section: The Alpha-1 Antitrypsin Protein and Human Reproductionmentioning

confidence: 99%

“…Changes in AAT concentration are a relevant factor in spontaneous as opposed to elective abortions. 16 Table 1. The main indications for diagnosing alpha-1 antitrypsin deficiency according to current recommendations 3,4 Emphysema, especially with early onset (before 45 years of age) Symptomatic form of chronic obstructive pulmonary disease, regardless of exposure to tobacco smoke Bronchial asthma with persistent airway obstruction Persistent airway obstruction confirmed by function tests and exposure to occupational factors or tobacco smoke, regardless of whether symptoms occur Bronchiectasis of unclear etiology Vasculitis with the presence of c-ANCAs Liver disease of unclear etiology Necrotizing panniculitis Family members with confirmed alpha-1 antitrypsin deficiency A family history of one of the aforementioned disorders…”

Section: Spontaneous Abortionsmentioning

confidence: 99%

Beyond the lungs: Alpha-1 antitrypsin’s potential role in human gestation

Jezela‐Stanek¹,

Chorostowska‐Wynimko²

2019

Adv Clin Exp Med

View full text Add to dashboard Cite

This study was performed as part of the scientific project-Dissemination and optimization of alpha-1 antitrypsin deficiency diagnostic algorithm in patients with chronic lung diseases (theme 5/4), National Institute of Tuberculosis and Lung Diseases, Warszawa, Poland. The authors are beholden to the Polish Foundation for Patients with Alpha-1 Antitrypsin Deficiency for their financial support of this research.

show abstract

“…In the context of pregnancy, it is worth noting that circulatory A1AT levels increase during the course of gestation ( 97 ), while low circulating levels are associated with both recurrent and spontaneous abortion ( 104 ), as well as cases with severe PE ( 105 ). As the latter pathologies are associated with overt neutrophil activity ( 61 , 76 ), it is currently unclear what the contribution of reduced A1AT levels is.…”

Section: A1at: Elastase Inhibitor or Modulator Of Neutrophil Activatimentioning

confidence: 99%

Excessive Neutrophil Activity in Gestational Diabetes Mellitus: Could It Contribute to the Development of Preeclampsia?

Vokálová

Breda

et al. 2018

Front. Endocrinol.

View full text Add to dashboard Cite

Gestational diabetes mellitus is a transient form of glucose intolerance occurring during pregnancy. Pregnancies affected by gestational diabetes mellitus are at risk for the development of preeclampsia, a severe life threatening condition, associated with significant feto-maternal morbidity and mortality. It is a risk factor for long-term health in women and their offspring. Pregnancy has been shown to be associated with a subliminal degree of neutrophil activation and tightly regulated generation of neutrophil extracellular traps (NETs). This response is excessive in cases with preeclampsia, leading to the presence of large numbers of NETs in affected placentae. We have recently observed that circulatory neutrophils in cases with gestational diabetes mellitus similarly exhibit an excessive pro-NETotic phenotype, and pronounced placental presence, as detected by expression of neutrophil elastase. Furthermore, exogenous neutrophil elastase liberated by degranulating neutrophils was demonstrated to alter trophoblast physiology and glucose metabolism by interfering with key signal transduction components. In this review we examine whether additional evidence exists suggesting that altered neutrophil activity in gestational diabetes mellitus may contribute to the development of preeclampsia.

show abstract

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

Cited by 23 publications

References 27 publications

Acute-phase protein α1-anti-trypsin: diverting injurious innate and adaptive immune responses from non-authentic threats

Acute-phase protein α1-anti-trypsin: diverting injurious innate and adaptive immune responses from non-authentic threats

Beyond the lungs: Alpha-1 antitrypsin’s potential role in human gestation

Excessive Neutrophil Activity in Gestational Diabetes Mellitus: Could It Contribute to the Development of Preeclampsia?

Contact Info

Product

Resources

About