scholarly journals Autoimmunity to the Lung Protective Phospholipid-Binding Protein Annexin A2 Predicts Mortality Among Hospitalized COVID-19 Patients

Author(s):  
Marisol Zuniga ◽  
Claudia Gomes ◽  
Steven E. Carsons ◽  
Michael T. Bender ◽  
Paolo Cotzia ◽  
...  

ABSTRACTBackgroundAnnexin A2 is a phospholipid-binding protein involved in fibrinolysis, cell membrane stabilization and repair, and ensuring the integrity of the pulmonary microvasculature. Given the autoantibodies observed in COVID-19 and that Annexin A2 is a known target of antiphospholipid antibodies, we studied autoimmunity directed against Annexin A2 among hospitalized COVID-19 patients.MethodsWe used ELISA to identify the levels of IgG autoantibodies recognizing Annexin A2 and A5 among 86 hospitalized cases of COVID-19. Using logistic regression, we analyzed the association between anti-Annexin A2 and A5 antibody levels with mortality after adjusting for age, sex, race and key comorbidities.ResultsWe found higher average levels of anti-Annexin A2 antibodies among hospitalized COVID-19 patients that died when compared with non-critical hospitalized COVID-19 patients (p-value = 0.006) and critically ill COVID-19 patients (p-value = 0.04). No significant differences in anti-Annexin A5 antibody levels were identified. Regression analysis showed that anti-Annexin A2 antibody levels as measured in relative units strongly predicted mortality with an odds ratio of 9.3 (95% CI: 1.9 to 44.6, p=0.005). In contrast, anti-Annexin A5 antibody levels were not associated with higher mortality (95% CI: 0.5 to 15.2, p=0.22).ConclusionsWe determined that anti-Annexin A2 antibodies were elevated among hospitalized COVID-19 patients and these levels predicted mortality. It is known that inhibition of Annexin A2 induces systemic thrombosis, cell death, and non-cardiogenic pulmonary edema. Autoimmunity to Annexin A2 is a potential mechanism that may explain the key clinical findings of severe COVID-19.

2016 ◽  
Vol 197 (4) ◽  
pp. 1252-1261 ◽  
Author(s):  
Sabriya Stukes ◽  
Carolina Coelho ◽  
Johanna Rivera ◽  
Anne E. Jedlicka ◽  
Katherine A. Hajjar ◽  
...  

2018 ◽  
Vol 39 (02) ◽  
pp. 203-207
Author(s):  
Michela Villani ◽  
Donatella Colaizzo ◽  
Pasquale Martinelli ◽  
Filomena Cappucci ◽  
Lucia Fischetti ◽  
...  

AbstractAntiphospholipid (aPL) antibodies are recognised risk factors for adverse obstetric outcomes. Recently, carriers of the M2 haplotype in the Annexin A5 gene have been shown to have a higher susceptibility to develop aPL antibodies. In a general obstetric population, we prospectively evaluated the possible relationship between: (1) aPL antibodies and M2 haplotype; and (2) aPL antibodies and/or M2 haplotype and obstetric outcomes. From a cohort of 3,097 consecutive pregnant women, 1,286 samples were analysed for the presence of both anti-cardiolipin and anti-human β2-glycoprotein I antibodies; samples with available DNA (n = 606) were also investigated for the M2 haplotype. Overall, 41/1,286 (3.2%) women showed the presence of aPL antibodies. Among them, 2 (4.8%) experienced a pregnancy loss and 38 (92.7%) gave birth to live-born babies (p-value = non-significant vs. those without aPL antibodies). M2 haplotype was identified in 140 (23.1%) out of 606 women with DNA available: 3/140 (2.1%) M2 carriers and 17/466 (3.6%) non-carriers tested positive for aPL antibodies, respectively (p-value = non-significant). In total, 15/150 (10%) M2 and/or aPL antibody carriers, and 38/445 (8.5%) non-aPL antibody and/or M2 carriers suffered from obstetric complications, respectively (p-value = non-significant). No relationship between aPL antibodies and M2 haplotype was found. Furthermore, neither aPL antibodies nor the M2 haplotype is associated with obstetric complications.


Author(s):  
Svetlana Varyukhina ◽  
Antonin Lamazière ◽  
Jean Louis Delaunay ◽  
Anaëlle de Wreede ◽  
Jesus Ayala-Sanmartin

Lupus ◽  
1998 ◽  
Vol 7 (2_suppl) ◽  
pp. 29-31 ◽  
Author(s):  
J Rauch

Lupus anticoagulant antibodies form a heterogeneous group of antiphospholipid antibodies with rather poorly defined antigens. The role that phospholipid-binding proteins play in lupus anticoagulant antibody activity is a subject of current investigation. Several candidate proteins have been proposed, including β2-glycoprotein I (β2GPI), prothrombin, and annexin V. As β2GPI-dependent lupus anticoagulants will be reviewed elsewhere in this issue, this paper will focus on the involvement of prothrombin and annexin V in lupus anticoagulant activity. Evidence for a role for these proteins in the reactivity and induction of lupus anticoagulant antibodies will be discussed, as well as an apparent requirement for both phospholipid and phospholipid-binding protein. The data presented here suggest that some lupus anticoagulant antibodies recognize and may be induced by complexes of phospholipid and phospholipid-binding proteins, in particular, phospholipid and prothrombin or annexin V.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Abdelrahman Zamzam ◽  
Muzammil H. Syed ◽  
John Harlock ◽  
John Eikelboom ◽  
Krishna K. Singh ◽  
...  

AbstractPlasma levels of fatty acid binding protein 3 (pFABP3) are elevated in patients with peripheral artery disease (PAD). Since the kidney filters FABP3 from circulation, we investigated whether urinary fatty acid binding protein 3 (uFABP3) is associated with PAD, and also explored its potential as a diagnostic biomarker for this disease state. A total of 130 patients were recruited from outpatient clinics at St. Michael’s Hospital, comprising of 65 patients with PAD and 65 patients without PAD (non-PAD). Levels of uFABP3 normalized for urine creatinine (uFABP3/uCr) were 1.7-folds higher in patients with PAD [median (IQR) 4.41 (2.79–8.08)] compared with non-PAD controls [median (IQR) 2.49 (1.78–3.12), p-value = 0.001]. Subgroup analysis demonstrated no significant effect of cardiovascular risk factors (age, sex, hypertension, hypercholesteremia, diabetes and smoking) on uFABP3/uCr in both PAD and non-PAD patients. Spearmen correlation studies demonstrated a significant negative correlation between uFABP3/uCr and ABI (ρ = − 0.436; p-value = 0.001). Regression analysis demonstrated that uFABP3/Cr levels were associated with PAD independently of age, sex, hypercholesterolemia, smoking, prior history of coronary arterial disease and Estimated Glomerular Filtration rate (eGFR) [odds ratio: 2.34 (95% confidence interval: 1.47–3.75) p-value < 0.001]. Lastly, receiver operator curve (ROC) analysis demonstrated unadjusted area under the curve (AUC) for uFABP3/Cr of 0.79, which improved to 0.86 after adjusting for eGFR, age, hypercholesteremia, smoking and diabetes. In conclusion, our results demonstrate a strong association between uFABP3/Cr and PAD and suggest the potential of uFABP3/Cr in identifying patients with PAD.


2017 ◽  
Vol 292 (42) ◽  
pp. 17407-17417 ◽  
Author(s):  
Kathryn C. Rahlwes ◽  
Stephanie A. Ha ◽  
Daisuke Motooka ◽  
Jacob A. Mayfield ◽  
Lisa R. Baumoel ◽  
...  

Author(s):  
Rania Khogli ELsidig Khogli ◽  
Abdel Rahim Mahmoud Muddathir ◽  
Alaa Eltayeb Omer ◽  
Lienda Bashier Eltayeb

Background: Repeated miscarriage can cause tissue injury can lead to the formation of antibodies to the phospholipids. Recurrent miscarriage (RM) is considering the one of the most common cause of sterility. Which has received more attention in recent years as a result of an increase in the number of reproductive-aged women. Materials and Methods: Plasma samples were tested for antiphospholipid antibodies using ELISA, and platelet count using Sysmex (KX21) Heamatology analyzer and Activated Partial Thromboplastin Time using semi-automated machine (STAGO PT31039352 (for coagulation). Results: The prevalence of Anti phospholipid antibodies (APL) was 30.5% in Sudanese patients with recurrent miscarriage, the prevalence of (Anti phospholipid Antibodies-IgM and IgG) was found to be 23.6% in patients with recurrent miscarriage compared to (Anti phospholipid Antibodies-IgG) was found to be 11.1% ((P value≤0.001), low platelets count (<50×109/l) observed in 10 (13.5%), as well as prolongation of activated partial thromboplastin time (APTT) among studied group were detected among 19 (26.1%). Conclusion: Higher prevalence of antiphospolidids antibodies, and acquired thrombophilia was detected among Sudanese women with recurrent abortion; The findings are concerning because they link an increased risk of thrombosis and a hypercoagulable state lead to recurrent miscarriage in pregnant women.


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