Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection.
Τίτλος | Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Gavriilaki, E., Tsiftsoglou S. A., Touloumenidou T., Farmaki E., Panagopoulou P., Michailidou E., Koravou E-E., Mavrikou I., Iosifidis E., Tsiatsiou O., Papadimitriou E., Papadopoulou-Alataki E., Papayanni P. Georgia, Varelas C., Kokkoris S., Papalexandri A., Fotoulaki M., Galli-Tsinopoulou A., Zafeiriou D., Roilides E., Sakellari I., Anagnostopoulos A., & Tragiannidis A. |
Journal | Curr Issues Mol Biol |
Volume | 44 |
Issue | 7 |
Pagination | 2811-2824 |
Date Published | 2022 Jun 28 |
ISSN | 1467-3045 |
Abstract | Complement dysregulation has been documented in adults with COVID-19 and implicated in relevant pediatric inflammatory responses against SARS-CoV-2. We propose that signatures of complement missense coding SNPs associated with dysregulation could also be identified in children with multisystem inflammatory syndrome (MIS-C). We investigated 71 pediatric patients with RT-PCR validated SARS-CoV-2 hospitalized in pediatric COVID-19 care units (November 2020-March 2021) in three major groups. Seven (7) patients suffered from MIS-C (MIS-C group), 32 suffered from COVID-19 and were hospitalized (admitted group), whereas 32 suffered from COVID-19, but were sent home. All patients survived and were genotyped for variations in the , , , , , , , , , , , , , , and genes. Upon evaluation of the missense coding SNP distribution patterns along the three study groups, we noticed similarities, but also considerably increased frequencies of the alternative pathway (AP) associated with SNPs rs12614 , rs1061170, and rs1065489 in the MIS-C patients. Our analysis suggests that the corresponding substitutions potentially reduce the C3b-inactivation efficiency and promote slower and weaker AP C3bBb pre-convertase assembly on virions. Under these circumstances, the complement AP opsonization capacity may be impaired, leading to compromised immune clearance and systemic inflammation in the MIS-C syndrome. |
DOI | 10.3390/cimb44070193 |
Alternate Journal | Curr Issues Mol Biol |
PubMed ID | 35877417 |
PubMed Central ID | PMC9325260 |
Grant List | Covid-19 / / Prefecture of Central Macedonia / IDG / / Pfizer Greece / |