Targeted genotyping of COVID-19 patients reveals a signature of complement C3 and factor B coding SNPs associated with severe infection.

Autor: Tsiftsoglou SA; Laboratory of Pharmacology, Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. Electronic address: stefanos.tsiftsoglou@gmail.com., Gavriilaki E; Hematology Department-BMT Unit, G. Papanicolaou Hospital, Exochi, Thessaloniki 57010, Greece. Electronic address: elenicelli@yahoo.gr., Touloumenidou T; Hematology Department-BMT Unit, G. Papanicolaou Hospital, Exochi, Thessaloniki 57010, Greece., Koravou EE; Hematology Department-BMT Unit, G. Papanicolaou Hospital, Exochi, Thessaloniki 57010, Greece., Koutra M; Hematology Department-BMT Unit, G. Papanicolaou Hospital, Exochi, Thessaloniki 57010, Greece., Papayanni PG; Hematology Department-BMT Unit, G. Papanicolaou Hospital, Exochi, Thessaloniki 57010, Greece., Karali V; Rheumatology and Clinical Immunology Unit, University General Hospital 'Attikon', Αthens, Greece., Papalexandri A; Hematology Department-BMT Unit, G. Papanicolaou Hospital, Exochi, Thessaloniki 57010, Greece., Varelas C; Hematology Department-BMT Unit, G. Papanicolaou Hospital, Exochi, Thessaloniki 57010, Greece., Chatzopoulou F; Microbiology Department, Aristotle University of Thessaloniki, Greece., Chatzidimitriou M; Biomedical Sciences Alexander Campus International Hellenic University, Thessaloniki, Greece., Chatzidimitriou D; Microbiology Department, Aristotle University of Thessaloniki, Greece., Veleni A; Infectious Disease Committee, G Papanicolaou Hospital, Thessaloniki, Greece., Rapti E; Laboratory of Hematology and Hospital Blood Transfusion Department, University General Hospital 'Attikon', NKUA, Medical School, Athens, Greece., Kioumis I; Respiratory Failure Department, G Papanicolaou Hospital-Aristotle University of Thessaloniki, Thessaloniki, Greece., Kaimakamis E; 1st Intensive Care Unit, G Papanicolaou Hospital, Thessaloniki, Greece., Bitzani M; 1st Intensive Care Unit, G Papanicolaou Hospital, Thessaloniki, Greece., Boumpas DT; Rheumatology and Clinical Immunology Unit, University General Hospital 'Attikon', Αthens, Greece., Tsantes A; Laboratory of Hematology and Hospital Blood Transfusion Department, University General Hospital 'Attikon', NKUA, Medical School, Athens, Greece., Sotiropoulos D; Hematology Department-BMT Unit, G. Papanicolaou Hospital, Exochi, Thessaloniki 57010, Greece., Papadopoulou A; Hematology Department-BMT Unit, G. Papanicolaou Hospital, Exochi, Thessaloniki 57010, Greece., Sakellari I; Hematology Department-BMT Unit, G. Papanicolaou Hospital, Exochi, Thessaloniki 57010, Greece., Kokoris S; Laboratory of Hematology and Hospital Blood Transfusion Department, University General Hospital 'Attikon', NKUA, Medical School, Athens, Greece., Anagnostopoulos A; Hematology Department-BMT Unit, G. Papanicolaou Hospital, Exochi, Thessaloniki 57010, Greece.
Jazyk: angličtina
Zdroj: Immunobiology [Immunobiology] 2023 Mar; Vol. 228 (2), pp. 152351. Date of Electronic Publication: 2023 Feb 15.
DOI: 10.1016/j.imbio.2023.152351
Abstrakt: We have attempted to explore further the involvement of complement components in the host COVID-19 (Coronavirus disease-19) immune responses by targeted genotyping of COVID-19 adult patients and analysis for missense coding Single Nucleotide Polymorphisms (coding SNPs) of genes encoding Alternative pathway (AP) components. We have identified a small group of common coding SNPs in Survivors and Deceased individuals, present in either relatively similar frequencies (CFH and CFI SNPs) or with stark differences in their relative abundance (C3 and CFB SNPs). In addition, we have identified several sporadic, potentially protective, coding SNPs of C3, CFB, CFD, CFH, CFHR1 and CFI in Survivors. No coding SNPs were detected for CD46 and CD55. Our demographic analysis indicated that the C3 rs1047286 or rs2230199 coding SNPs were present in 60 % of all the Deceased patients (n = 25) (the rs2230199 in 67 % of all Deceased Males) and in 31 % of all the Survivors (n = 105, p = 0.012) (the rs2230199 in 25 % of all Survivor Males). When we analysed these two major study groups using the presence of the C3 rs1047286 or rs2230199 SNPs as potential biomarkers, we noticed the complete absence of the protective CFB rs12614 and rs641153 coding SNPs from Deceased Males compared to Females (p = 0.0023). We propose that in these individuals, C3 carrying the R102G and CFB lacking the R32W or the R32Q amino acid substitutions, may contribute to enhanced association dynamics of the C3bBb AP pre-convertase complex assembly, thus enabling the exploitation of the activation of the Complement Alternative pathway (AP) by SARS-CoV-2.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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