scholarly journals SARS-CoV2- infection as a trigger of humoral response against apolipoprotein A-1

2021 ◽  
Author(s):  
Sabrina Pagano ◽  
Sabine Yerly ◽  
Benjamin Meyer ◽  
Catherine Juillard ◽  
Noémie Suh ◽  
...  
Keyword(s):  
General Population ◽  
Molecular Mimicry ◽  
Humoral Response ◽  
Cross Reactivity ◽  
High Density Lipoproteins ◽  
Major Protein ◽  
Prognostic Accuracy ◽  
Apolipoprotein A ◽  
General Population Cohort ◽  
Mimic Peptide

ABSTRACTAimsUnravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. We want to determine whether SARS-CoV-2 exposure could trigger a humoral response against apolipoprotein A-1 (anti-apoA-1 IgG) through molecular mimicry and assess its relationship to patient prognosis.Methods and ResultsAnti-Spike domain 1 (SD1) IgGs, anti-apoA-1 IgGs and against mimic peptides, as well as cytokines were assessed by immunoassays on a case-control (n=101), an intensive care unit (ICU; n=126) with a 28-days follow-up, and a general population cohort (n=663) with available samples in the pre and post-pandemic period. Linear sequence homologies and antibodies cross-reactivity between apoA-1, TLR2, and Spike epitopes were identified. Overall, anti-apoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (p<0.0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines, and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-days kinetics, reaching 82% for anti-apoA-1 seropositivity. C-statistics (CS) indicated that anti-Spike/TLR2 mimic-peptide IgGs displayed a significant prognostic accuracy for overall mortality at 28 days (CS: 0.64; p=0.02). In the general population, SARS-CoV-2 exposure increased baseline anti-apoA-1 IgG levels.ConclusionsCOVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.

scholarly journals Sars-CoV2- infection as a trigger of humoral response against apolipoprotein A-1

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Pagano ◽  
S Yerly ◽  
N Suh ◽  
C Le Terrier ◽  
L Farrera-Soler ◽  
...  
Keyword(s):  
Public Health ◽  
General Population ◽  
Molecular Mimicry ◽  
Humoral Response ◽  
Public Institution ◽  
High Density Lipoproteins ◽  
Major Protein ◽  
Apolipoprotein A ◽  
Overall Mortality

Abstract Background Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. SARS-CoV-2 autoimmune-mediated inflammation have been reported, but the existence of autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) in COVID-19 remains unexplored. Anti-apoA-1 IgGs have emerged as an independent biomarker for cardiovascular disease and mortality in humans with proinflammatory and proatherogenic functions in vivo and in vitro. Purpose We want to determine i) the degree of homology between SARS-CoV-2, apoA-1, and Toll-like receptor-2 (TLR2) epitopes, ii) the association between anti-SARSCoV2 and anti-apoA-1 IgGs, and iii) their relationship to prognosis. Methods We performed bioinformatics modelling coupled with mimetic peptides engineering, as well as functional and competition assays with antibodies to identify molecular mimicry between SARS-CoV-2, apoA-1 and TLR2 epitopes. Anti-Spike domain 1 (SD1) IgGs, anti-apoA-1 IgGs and against mimic peptides, as well as cytokines were assessed by immunoassays on a case-control (n=101), an intensive care unit (ICU; n=126) with a 28-days follow-up for overall mortality, and a general population cohort (n=663) with available samples in the pre and post-pandemic period. Results Linear sequence homologies and antibodies cross-reactivity between apoA-1, TLR2, and Spike epitopes were identified. Overall, anti-apoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (p&lt;0.0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines, and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-days kinetics, reaching 82% for anti-apoA-1 seropositivity. C-statistics (CS) indicated that baseline anti-Spike/TLR2 mimic-peptide IgGs displayed a significant prognostic accuracy for overall mortality at 28 days (CS: 0.64; p=0.02). In the general population, SARS-CoV-2 exposure increased baseline anti-apoA-1 IgG levels. Conclusions COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This study was funded by the Swiss Federal Office of Public Health, Swiss School of Public Health (Corona Immunitas research program), the Fondation de Bienfaisance du Groupe Pictet, the Fondation Ancrage, the Fondation Privée des HUG, and the Center for Emerging Viral Diseases. The De Reuter (grant Nr 657) and the Schmidheiny Foundation.

scholarly journals Anti-apolipoprotein A-1 autoantibodies correlate with disease activity in systemic lupus erythematosus

Rheumatology ◽  
2019 ◽  
Author(s):  
Haïg Nigolian ◽  
Camillo Ribi ◽  
Delphine S Courvoisier ◽  
Sabrina Pagano ◽  
Montserrat Alvarez ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Reverse Cholesterol Transport ◽  
Clinical Performance ◽  
Antioxidant Properties ◽  
Cross Reactivity ◽  
High Density Lipoproteins ◽  
Cholesterol Transport ◽  
Apolipoprotein A ◽  
Laboratory Markers

Abstract Objectives Apolipoprotein A-1 (ApoA-1) is a protein fraction of the high-density lipoproteins with anti-inflammatory and antioxidant properties that play a major role in reverse cholesterol transport. The presence of anti-ApoA-1 IgG has been reported in SLE to be variably associated with disease activity or cardiovascular events (CVEs). We assessed the clinical performance of anti-ApoA-1 IgG and of antibodies directed against its immunodominant F3L1 peptide (F3L1 IgG) in a well-characterized Swiss SLE cohort study. Methods A total of 354 biological samples and interviews from 176 individuals were studied. SLEDAI, clinical characteristics, anamnestic CVEs and therapy details were recorded. Sera were tested for the presence of anti-ApoA-1 IgG, anti-F3L1 IgG, anti-dsDNA IgG and aPL. Results Anti-ApoA-1 and anti-F3L1 IgG positivity was associated with higher SLEDAI, mostly due to concomitant positivity of dsDNA IgG and low complement. Variations in time of anti-ApoA-1 IgG correlated positively with variations of anti-dsDNA IgG and inversely to variations of C3 levels. No cross-reactivity was found between anti-ApoA-1 and anti-dsDNA IgG. Positivity for anti-Apo-A1 IgG was more frequent in individuals receiving 10 mg/day or more of prednisone. We did not find any significant association between anti-ApoA-1 IgG positivity and CVEs. Conclusion Anti-ApoA-1 and anti-F3L1 IgG in SLE correlate strongly with laboratory markers of activity, particularly with the presence and titre of dsDNA IgG. These results confirm and extend previous findings and support the use of anti-ApoA1 IgG in the clinical setting. Their role in CVEs deserves further investigation.

scholarly journals Reference intervals for plasma apolipoprotein A-1 determined with a standardized commercial immunoturbidimetric assay: results from the Framingham Offspring Study

1996 ◽  
Vol 42 (4) ◽  
pp. 507-514 ◽  
Author(s):  
J Contois ◽  
J R McNamara ◽  
C Lammi-Keefe ◽  
P W Wilson ◽  
T Massov ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
White Men ◽  
Reference Intervals ◽  
High Density Lipoproteins ◽  
Major Protein ◽  
Reference Ranges ◽  
Men And Women ◽  
Apolipoprotein A ◽  
The Mean ◽  
Plasma Apolipoprotein

Abstract We have evaluated a commercially available, standardized immunoturbidimetric assay of apolipoprotein (apo) A-I, the major protein constituent of high-density lipoproteins (HDL). We determined the reference ranges of plasma apo A-I concentration for white men and women and related these values to the risk of coronary heart disease (CHD). The mean between-run CV for this assay was 2.9%. As determined with individuals participating cycle 4 of the Framingham Offspring Study, the mean (+/- SD) apo A-I concentration was 13% lower in 1879 men (1.34 +/- 0.23 g/L) than in 1939 women (1.54 +/- 0.28 g/L) (P&lt;0.001). An apo A-I concentration of 1.20 g/L roughly corresponded to the 25th percentile value in men and the 5th percentile in women, and subjects with a concentration below this value were significantly more likely to have CHD than subjects wit a higher concentration (P&lt;0.001).

Characterization of a monoclonal antibody (HB-22) and development of an ELISA for human apolipoprotein A-I

1995 ◽  
Vol 41 (8) ◽  
pp. 1150-1158 ◽  
Author(s):  
T C Rothwell ◽  
V S Kamanna ◽  
F Y Jin ◽  
E Koren ◽  
T Foley ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Binding Capacity ◽  
Cross Reactivity ◽  
High Density Lipoproteins ◽  
Tween 20 ◽  
Major Protein ◽  
Binding Studies ◽  
Very Low Density Lipoproteins ◽  
Human Apolipoprotein

Abstract We describe the production and characterization of a high-affinity monoclonal antibody, HB-22, for apolipoprotein (apo) A-I, a major protein of human high-density lipoproteins (HDL). Including Tween 20 in the reaction mixture increased the binding capacity of HB-22 to apo A-I. HB-22 showed monospecific reactivity with HDL or apo A-I, displaying no cross-reactivity with apo A-II, intermediate-, low-, or very-low-density lipoproteins. Immunoaffinity columns with HB-22 (in the absence of Tween 20) showed an immunosorbent capacity of 80 micrograms of apo A-I per milligram of antibody. The immunosorbent capacity of HB-22 for apo A-I was similar in plasma samples from normolipidemic, hypercholesterolemic, or hypertriglyceridemic patients. Comparative binding studies demonstrated that compared with other available monoclonal apo A-I antibodies, HB-22 had the greatest apparent affinity for binding to HDL. A competitive ELISA developed by utilizing HB-22 could detect as little as 20 ng of apo A-I in the reaction mixture. The intra- and interassay CVs of the ELISA were 5.4% and 9.5%, respectively.

Human apolipoprotein A-I: structure determination and analysis of unusual diffraction characteristics

1999 ◽  
Vol 55 (12) ◽  
pp. 2013-2021 ◽  
Author(s):  
David W. Borhani ◽  
Jeffrey A. Engler ◽  
Christie G. Brouillette
Keyword(s):  
Structure Determination ◽  
Density Lipoprotein ◽  
High Density ◽  
High Density Lipoproteins ◽  
Major Protein ◽  
Data Set ◽  
Cholesterol Acyl Transferase ◽  
Cell Parameters ◽  
Human Apolipoprotein ◽  
Apolipoprotein A

The crystallization and structure determination of recombinant human apolipoprotein A-I (apo A-I), the major protein component of high-density lipoprotein, is described. The fragment crystallized, residues 44–243 of native apo A-I [apo Δ(1–43)A-I], is very similar to intact native apo A-I in its ability to bind lipid, to be incorporated into high-density lipoproteins and to activate lecithin–cholesterol acyl transferase. Apo Δ(1–43)A-I crystallizes from 1.0–1.4 M sodium citrate pH 6.5–7.5 in space group P212121, with unit-cell parameters a = 97.47, b = 113.87, c = 196.19 Å (crystal form I). The crystals exhibit unusual diffraction intensity spikes and axial extinctions that are discussed in the context of the 4 Å crystal structure. When flash-cooled to 100 K, the crystals diffract synchrotron radiation to 3 Å resolution. Radiation sensitivity and crystal-to-crystal variation have hindered the assembly of a complete 3 Å data set.

scholarly journals Apolipoprotein A-I (ApoA-I), Immunity, Inflammation and Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1097 ◽  
Author(s):  
Georgila ◽  
Vyrla ◽  
Drakos
Keyword(s):  
Cancer Biology ◽  
Animal Studies ◽  
High Density Lipoproteins ◽  
Major Protein ◽  
Multifunctional Protein ◽  
Cancer Pathogenesis ◽  
Early Cancer Diagnosis ◽  
Apolipoprotein A

Apolipoprotein A-I (ApoA-I), the major protein component of high-density lipoproteins (HDL) is a multifunctional protein, involved in cholesterol traffic and inflammatory and immune response regulation. Many studies revealing alterations of ApoA-I during the development and progression of various types of cancer suggest that serum ApoA-I levels may represent a useful biomarker contributing to better estimation of cancer risk, early cancer diagnosis, follow up, and prognosis stratification of cancer patients. In addition, recent in vitro and animal studies disclose a more direct, tumor suppressive role of ApoA-I in cancer pathogenesis, which involves anti-inflammatory and immune-modulatory mechanisms. Herein, we review recent epidemiologic, clinicopathologic, and mechanistic studies investigating the role of ApoA-I in cancer biology, which suggest that enhancing the tumor suppressive activity of ApoA-I may contribute to better cancer prevention and treatment.

scholarly journals The Mechanism of Bisphenol A Atherogenicity Involves Apolipoprotein A-I Downregulation through NF-κB Activation

2019 ◽  
Vol 20 (24) ◽  
pp. 6281
Author(s):  
Violeta G. Trusca ◽  
Madalina Dumitrescu ◽  
Ioana M. Fenyo ◽  
Irina F. Tudorache ◽  
Maya Simionescu ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Hdl Cholesterol ◽  
Dna Interaction ◽  
Inhibitory Effect ◽  
Environmental Chemicals ◽  
High Density Lipoproteins ◽  
Major Protein ◽  
Dependent Manner ◽  
Atherosclerotic Lesions ◽  
Apolipoprotein A

Apolipoprotein A-I (apoA-I) is the major protein component of high-density lipoproteins (HDL), mediating many of its atheroprotective properties. Increasing data reveal the pro-atherogenic effects of bisphenol A (BPA), one of the most prevalent environmental chemicals. In this study, we investigated the mechanisms by which BPA exerts pro-atherogenic effects. For this, LDLR−/− mice were fed with a high-fat diet and treated with 50 µg BPA/kg body weight by gavage. After two months of treatment, the area of atherosclerotic lesions in the aorta, triglycerides and total cholesterol levels were significantly increased, while HDL-cholesterol was decreased in BPA-treated LDLR−/− mice as compared to control mice. Real-Time PCR data showed that BPA treatment decreased hepatic apoA-I expression. BPA downregulated the activity of the apoA-I promoter in a dose-dependent manner. This inhibitory effect was mediated by MEKK1/NF-κB signaling pathways. Transfection experiments using apoA-I promoter deletion mutants, chromatin immunoprecipitation, and protein-DNA interaction assays demonstrated that treatment of hepatocytes with BPA induced NF-κB signaling and thus the recruitment of p65/50 proteins to the multiple NF-κB binding sites located in the apoA-I promoter. In conclusion, BPA exerts pro-atherogenic effects downregulating apoA-I by MEKK1 signaling and NF-κB activation in hepatocytes.

Crystallization of truncated human apolipoprotein A-I in a novel conformation

1999 ◽  
Vol 55 (9) ◽  
pp. 1578-1583 ◽  
Author(s):  
David W. Borhani ◽  
Jeffrey A. Engler ◽  
Christie G. Brouillette
Keyword(s):  
Diffraction Limit ◽  
Unit Cell ◽  
High Density ◽  
High Density Lipoproteins ◽  
Original Form ◽  
Major Protein ◽  
Cholesterol Acyl Transferase ◽  
Space Group ◽  
Human Apolipoprotein ◽  
Apolipoprotein A

The crystallization of recombinant human apolipoprotein A-I (apo A-I), the major protein component of high-density lipoprotein, in a new crystal form is described. The fragment crystallized, residues 44–243 of native apo A-I [apo Δ(1–43)A-I], is very similar to intact native apo A-I in its ability to bind lipid, to be incorporated into high-density lipoproteins and to activate lecithin–cholesterol acyl transferase. Apo Δ(1–43)A-I crystallizes, in the presence of β-D-octylglucopyranoside, in space group I222 or I212121, with unit-cell parameters a = 37.11, b = 123.62, c = 164.65 Å and a diffraction limit of 3.2 Å. These form II crystals grow under conditions of significantly lower ionic strength than the original form I crystals (space group P212121, a = 97.47, b = 113.87, c = 196.19 Å, diffraction limit 3.0 Å). Packing arguments show that the unusual open conformation of apo Δ(1–43)A-I found in the form I crystals cannot be packed into the smaller oddly proportioned form II unit cell. Monomeric apo Δ(1–43)A-I, as either a four-helix bundle (∼75 × 30 × 30 Å) or an extended helical rod (∼150 × 20 × 20 Å), can be packed into the form II unit cell. It is concluded, therefore, that apo Δ(1–43)A-I may have crystallized in one of these distinct conformations in the form II crystals.

scholarly journals Importance of Apolipoprotein A-I and A-II Composition in HDL and Its Potential for Studying COVID-19 and SARS-CoV-2

Medicines ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 38
Author(s):  
Kyung-Hyun Cho
Keyword(s):  
Antiviral Activity ◽  
High Density ◽  
High Density Lipoproteins ◽  
Potent Antiviral Activity ◽  
Apolipoprotein A ◽  
Putative Role

The composition and properties of apolipoprotein (apo) A-I and apoA-II in high-density lipoproteins (HDL) might be critical to SARS-CoV-2 infection via SR-BI and antiviral activity against COVID-19. HDL containing native apoA-I showed potent antiviral activity, while HDL containing glycated apoA-I or other apolipoproteins did not. However, there has been no report to elucidate the putative role of apoA-II in the antiviral activity of HDL.

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