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):  
Humoral Response ◽  
Apolipoprotein A

scholarly journals SARS-COV2- infection as a trigger of humoral response against apolipoprotein A-1

2021 ◽  
Vol 331 ◽  
pp. e78
Author(s):  
S. Pagano ◽  
S. Yery ◽  
B. Meyer ◽  
C. Juillard ◽  
N. Suh ◽  
...  
Keyword(s):  
Humoral Response ◽  
Apolipoprotein A

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<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 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 Anti‐SARS‐CoV‐2 mRNA vaccines as inducers of humoral response against apolipoprotein A‐1?

2021 ◽  
Author(s):  
Nicolas Vuilleumier ◽  
Sabrina Pagano ◽  
Burkhard Ludewig ◽  
Kristin Schmiedeberg ◽  
Christoph Haller ◽  
...  
Keyword(s):  
Humoral Response ◽  
Apolipoprotein A

Regulation of intestinal apolipoprotein A-IV synthesis

1998 ◽  
Vol 13 (11-s4) ◽  
pp. S270-S274
Author(s):  
P TSO ◽  
L YAO ◽  
S ZHENG ◽  
L EE
Keyword(s):  
Apolipoprotein A

Lp(a): der akzeptierte unabhängige Risikofaktor

2019 ◽  
Vol 23 (09) ◽  
pp. 388-391
Author(s):  
Volker Schettler
Keyword(s):  
Lipoprotein A ◽  
Apolipoprotein A ◽  
Apolipoprotein B100

Lipoprotein(a) (Lp(a)) besteht aus einem LDL-Partikel, an dem über das Apolipoprotein B100 des Partikels eine Disulfidbrücke zu einem Apolipoprotein(a) besteht ( Abb. 1 ). Obwohl Lp(a) bereits 1963 von Berg et al. erstmals als „lipoprotein associated antigen“ entdeckt 1 und schon früh ein Zusammenhang mit kardiovaskulären Ereignissen diskutiert wurde 2, konnten diese Annahmen der klinischen Eigenschaften erst deutlich später im Rahmen von epidemiologischen Evaluationen bestätigt werden 3, 4. Ab einer Lp(a)-Konzentration von über 30 mg/dl (> 75 nmol/l) besteht ein nahezu linearer Zusammenhang zwischen dem Anstieg der Lp(a)-Konzentration und kardiovaskulären Ereignissen wie Myokardinfarkt und das Risiko für eine Aortenklappenstenose 3, 4.

Apolipoprotein(a), Fibrinopeptide A and Carotid Atherosclerosis in Middle-Aged Men

1994 ◽  
Vol 72 (04) ◽  
pp. 563-566 ◽  
Author(s):  
Tuomo Rankinen ◽  
Sari Väisänen ◽  
Michele Mercuri ◽  
Rainer Rauramaa
Keyword(s):  
Risk Factors ◽  
Cardiovascular Diseases ◽  
Carotid Atherosclerosis ◽  
Intima Media Thickness ◽  
Carotid Bifurcation ◽  
Carotid Intima Media Thickness ◽  
Fibrinopeptide A ◽  
Carotid Imt ◽  
Apolipoprotein A ◽  
The Difference

SummaryThe association between apolipoprotein(a) [apo(a)], fibrinogen, fibrinopeptide A (FPA) and carotid intima-media thickness (IMT) was analyzed in Eastern Finnish men aged 50 to 60 years. Apo(a) correlated directly with carotid bifurcation (r = 0.26, p = 0.001), but not with common carotid IMT. Men in the lowest quartile of apo(a) had thinner (p = 0.013) IMT in bifurcation [1.59 mm (95% Cl 1.49; 1.68)] compared to the men in the highest [1.91 mm (95% Cl 1.73; 2.09)] apo(a) quartile. The difference remained (p=0.038) after adjusting for confounders. Plasma fibrinogen was not related to carotid IMT, whereas FPA correlated with common carotid (r = 0.21, p = 0.016) and carotid bifurcation (r = 0.21, p = 0.018) IMT. These associations abolished after adjusting for the confounders. The data suggest that apo(a) associate with carotid atherosclerosis independent of other risk factors for ischemic cardiovascular diseases.

The Identification and Significance of a Thr→Pro Polymorphism in Kringle IV Type 8 of Apolipoprotein(a)

1997 ◽  
Vol 77 (05) ◽  
pp. 0949-0954 ◽  
Author(s):  
J Prins ◽  
F R Lues ◽  
Y Y van der Hoek ◽  
J J.P Kastelein ◽  
B N Bouma ◽  
...  
Keyword(s):  
Case Control Study ◽  
Amino Acid Position ◽  
Case Control ◽  
Binding Studies ◽  
Binding Characteristics ◽  
Apolipoprotein A ◽  
Significant Independent Risk Factor ◽  
And Gender ◽  
Control Study

SummaryElevated plasma levels of lipoprotein(a) [Lp(a)] represent a significant independent risk factor for the development of atherosclerosis. Interindividual levels of apo(a) vary over 1000-fold and are mainly due to inheritance that is linked to the locus of the apolipoprotein(a) [apo(a)] gene. The apo(a) gene encodes multiple repeats of a sequence exhibiting up to 85% DNA sequence homology with plasminogen kringle IV (K.IV), a lysine binding domain. In our search for sequence polymorphisms in the K.IV coding domain, we identified a polymorphism predicting a Thr→Pro substitution located at amino acid position 12 of kringle IV type 8 of apo(a). The functional and clinical significance of this polymorphism was analysed in a case-control study and by comparing the in vitro lysine binding characteristics of the two Lp(a) subtypes.The case-control study (involving 153 subjects having symptomatic atherosclerosis and 153 age and gender matched normolipidemic controls) revealed an overall allele frequency for the Thr12-→Pro substitution in kringle IV type 8 of 14% and a negative association between presence of the Pro12-subtype and symptomatic atherosclerosis (p <0.03). The in vitro lysine binding studies, using Lp(a) isolated from subjects homozygous for either Thr12 or Pro12 in K.IV type 8, revealed comparable lysine-Sepharose binding fractions for the two subtypes. The binding affinity (Kd) for immobilised plasmin degraded des- AA-fibrin (DesafibTM-X) was also comparable for the two subtypes, however a decreased maximal attainable binding (Bmax) for immobilised desafibTM-X was observed for the Pro12-subtype Lp(a).

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