Conference Presentation
Reference
SARS-COV2- infection as a trigger of humoral response against apolipoprotein A-1
PAGANO, Sabrina, et al.
Abstract
Background and Aims: 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. 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: 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, 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
PAGANO, Sabrina, et al . SARS-COV2- infection as a trigger of humoral response against apolipoprotein A-1. In: EAS Congress 2021 , Virtual Congress, May 30 - June 02, 2021, p. e78
DOI : 10.1016/j.atherosclerosis.2021.06.227
Available at:
http://archive-ouverte.unige.ch/unige:155229
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Methods:Using ourknock out/knock inreporter mouse we performed a bone marrow transplantation, transplanting Apoe-/- bone marrow into Apoe-/- and Apoe-/-ChemR23eGFP/eGFP mice respectively and after were placed on a Western diet for 6 weeks. To further unravel phenotypic consequences of ChemR23 deficiency on vascular endothelial (EC) and smooth muscle cells (VSMC) we will perform immunohistochemial stainings and mRNA expression analysis in aortic arches and aortic roots of animals lacking somatic ChemR23 andApoe-/-control mice. In parallel, human EC/VSMCs will be culturedin vitroin absence and presence of different ligands, with and without ChemR23 inhibition.
Results:Our data demonstrated that a lack of ChemR23 on somatic cells, resulted in a significantly increased lesion sizes and lesional macrophage infiltration.
Conclusions:Our novel data points at an atheroprotective role of somatic -most likely vascular- ChemR23 expression, suggesting that ChemR23 or- chestrates an anti-inflammatory response in vascular endothelial and smooth muscle cells. Our ongoing research aims at identifying the key signaling pathways of ChemR23 which mediate either the pro- or anti- inflammatory responses.
P068 / #445, E-POSTERS TOPIC:1. PATHOGENESIS OF ATHEROSCLEROSIS / 1.04 INFLAMMATION, IMMUNITY AND INFECTION IN ATHEROSCLEROSIS.
SARS-COV2- INFECTION AS A TRIGGER OF HUMORAL RESPONSE AGAINST APOLIPOPROTEIN A-1
S. Pagano1, S. Yery1, B. Meyer2, C. Juillard1, N. Suh3, C. Le Terrier3, J.-P.
Daguer4, F.-S. Lluc5, S. Barluenga4, G. Piumatti6, O. Hartley7, B.
Lemaitre1, C.S. Eberhardt2, C.-A. Siegrist8, I. Eckerle9, S. Stringhini6, I.
Guessous6, L. Kaiser10, J. Pugin3, N. Winssinger4, N.
Vuilleumier1. 1Geneva University Hospitals, Department Of Diagnostics, Geneva, Switzerland; 2University of Geneva, Centre For Vaccinology, Department Of Pathology And Immunology, Geneva, Switzerland;3Geneva University Hospitals, Division Of Intensive Care, Geneva, Switzerland;
4Faculty of Science, University of Geneva, Department Of Organic Chemistry, Nccr Chemical Biology, Geneva, Switzerland; 5University of Geneva, Department Of Organic Chemistry, Nccr Chemical Biology, Geneva, Switzerland; 6Geneva University Hospitals, Division And Department Of Primary Care Medicine, Geneva, Switzerland; 7University of Geneva, Department Of Pathology And Immunology, Geneva, Switzerland;8Geneva University Hospitals, Departments Of Pathology-immunology And Pediatrics, Geneva, Switzerland; 9Geneva University Hospitals, Geneva Centre For Emerging Viral Diseases, Geneva, Switzerland; 10Geneva University Hospitals, Division Of Laboratory Medicine, Department Of Diagnostics And Of Medical Specialties, Division Of Infectious Diseases., Geneva, Switzerland
Background and Aims: 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. We want to determine whether SARS-CoV-2 exposure could trigger a humoral response against apolipo- protein A-1 (anti-apoA-1 IgG) through molecular mimicry and assess its relationship to patient prognosis.
Methods: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 (n¼101), an intensive care unit (ICU; n¼126) with a 28-days follow-up, and a general population cohort (n¼663) with available sam- ples in the pre and post-pandemic period.
Results:Linear sequence homologies and antibodies cross-reactivity be- tween 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 sero- negative 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; p¼0.02). 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 prog- nosis 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.
P069 / #538, E-POSTERS TOPIC:1. PATHOGENESIS OF ATHEROSCLEROSIS / 1.04 INFLAMMATION, IMMUNITY AND INFECTION IN ATHEROSCLEROSIS.
ASSOCIATION OF THE RS17574 DPP4 POLYMORPHISM WITH PREMATURE CORONARY ARTERY DISEASE IN DIABETIC SUBJECTS.
RESULTS FROM THE COHORT OF THE GEA MEXICAN STUDY.
R. Posadas-Sanchez1, M.D.C. Gonzalez-Salazar1, C. Vazquez- Vazquez2, G.C. Cardoso-Salda~na1, G. Vargas-Alarcon3.1Instituto Nacional de Cardiologia, Endocrinología, Ciudad de Mexico, Mexico; 2Instituto Nacional de Cardiologia, Biologia Molecular, Ciudad de Mexico, Mexico;
3Instituto Nacional de Cardiologia, Biología Molecular, Ciudad de Mexico, Mexico
Background and Aims:We previously showed that rs17574DDP4poly- morphism is associated with hypoalphalipoproteinemia (HA). Considering that HA is often present in diabetic patients and is a risk factor for pre- mature coronary artery disease (pCAD), we evaluate the association of this polymorphism with pCAD in diabetic (pCAD+DM) patients.
Methods:The rs17574 polymorphism was genotyped in 405 pCAD+DM participants and, 852 non-pCAD, nondiabetic normoglycemic individuals as the control group. The associations were evaluated using logistic regression analyses. DPP4 serum concentrations were measured in 339 pCAD+DM subjects and 818 control individuals.
Results:Under inheritance models adjusted for confounding variables, the rs17574 polymorphism was associated with lower risk of the presence pCAD (OR¼0.68, Padditive¼0.007; OR¼0.61, Pdominant¼0.003, OR¼0.61 Pheterocygote¼0.003, OR¼0.60 Pcodominant1¼0.003). DPP4 concentration was higher in controls when compared with pCAD+DM participants (122[94- 155] ng/mL vs 93[70-122] ng/mL, respectively, P<0.001). DPP4 levels in the whole sample were analyzed stratifying for rs17574 DPP4 genotypes.
Carriers of the rs17574AAgenotype have the highest DPP4 concentration (115[87-148] ng/mL) compared withAG(112[86-143] ng/mL) andGGge- notypes (110[74-142] ng/mL, P¼0.004). However, when same analyses were done separately in both groups, significant differences were observed only in the pCAD+DM group; subjects withAAgenotype had the highest DPP4 concentration (96[72-123] ng/mL) compared withAG(89[64-114]
ng/mL) andGGgenotypes (73[59-92], P¼0.037).
Conclusions:Our data suggest that the rs17574G DPP4allele could be envisaged as a protective genetic marker for pCAD in diabetic subjects.
DPP4 levels were lower in the pCAD+DM individuals and the rs17574GG genotype was associated with the lowest DPP4 levels. CONACyT CB-2016- 01-286065
P070 / #577, E-POSTERS TOPIC:1. PATHOGENESIS OF ATHEROSCLEROSIS / 1.04 INFLAMMATION, IMMUNITY AND INFECTION IN ATHEROSCLEROSIS.
HIV-INFECTED PATIENTS DISPLAY INCREASED PROATHEROGENIC ANTI- APOLIPOPROTEIN A1 AUTOANTIBODIES, INFLAMMATORY AND METABOLOMIC MARKERS
M. Frias1, N. Berarpour2, S. Pagano3,4, J. Sidibe2, F. Kamau5, S. Lecour6, H.
Strijdom5, A. Thomas2, N. Vuilleumier1,3.1Univeristy Hospital of Geneva, Medical Specialties, Geneva, Switzerland; 2Unit of Toxicology, University Centre Of Legal Medicine, Geneva, Switzerland; 3Geneva University Hospitals, Department Of Diagnostics, Geneva, Switzerland; 4Geneva University Hospital, Diagnostic Department, Geneva, Switzerland;
5Stellenbosch University, Division Of Medical Physiology, Cape Town, South Africa; 6University of Cape Town, Hatter Institute For Cardiovascular Research In Africa, Cape Town, South Africa
Abstracts / Atherosclerosis 331 (2021) e56ee293 e78
