Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection
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 infla...
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2022-06-01
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| author | Eleni Gavriilaki Stefanos A. Tsiftsoglou Tasoula Touloumenidou Evangelia Farmaki Paraskevi Panagopoulou Elissavet Michailidou Evaggelia-Evdoxia Koravou Ioulia Mavrikou Elias Iosifidis Olga Tsiatsiou Eleni Papadimitriou Efimia Papadopoulou-Alataki Penelope Georgia Papayanni Christos Varelas Styliani Kokkoris Apostolia Papalexandri Maria Fotoulaki Assimina Galli-Tsinopoulou Dimitrios Zafeiriou Emmanuel Roilides Ioanna Sakellari Achilles Anagnostopoulos Athanasios Tragiannidis |
| author_facet | Eleni Gavriilaki Stefanos A. Tsiftsoglou Tasoula Touloumenidou Evangelia Farmaki Paraskevi Panagopoulou Elissavet Michailidou Evaggelia-Evdoxia Koravou Ioulia Mavrikou Elias Iosifidis Olga Tsiatsiou Eleni Papadimitriou Efimia Papadopoulou-Alataki Penelope Georgia Papayanni Christos Varelas Styliani Kokkoris Apostolia Papalexandri Maria Fotoulaki Assimina Galli-Tsinopoulou Dimitrios Zafeiriou Emmanuel Roilides Ioanna Sakellari Achilles Anagnostopoulos Athanasios Tragiannidis |
| author_sort | Eleni Gavriilaki |
| collection | DOAJ |
| description | 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 <i>C3</i>, <i>C5</i>, <i>CFB</i>, <i>CFD</i>, <i>CFH</i>, <i>CFHR1</i>, <i>CFI</i>, <i>CD46</i>, <i>CD55</i>, <i>MASP1</i>, <i>MASP2</i>, <i>MBL2</i>, <i>COLEC11</i>, <i>FCN1</i>, and <i>FCN3</i> 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 <i>CFB</i>, rs1061170, and rs1065489 <i>CFH</i> 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. |
| first_indexed | 2024-03-09T12:04:17Z |
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| last_indexed | 2024-03-09T12:04:17Z |
| publishDate | 2022-06-01 |
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| series | Current Issues in Molecular Biology |
| spelling | doaj.art-026382604f88499ab0ee29b1303b58912023-11-30T22:59:27ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-06-014472811282410.3390/cimb44070193Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 InfectionEleni Gavriilaki0Stefanos A. Tsiftsoglou1Tasoula Touloumenidou2Evangelia Farmaki3Paraskevi Panagopoulou4Elissavet Michailidou5Evaggelia-Evdoxia Koravou6Ioulia Mavrikou7Elias Iosifidis8Olga Tsiatsiou9Eleni Papadimitriou10Efimia Papadopoulou-Alataki11Penelope Georgia Papayanni12Christos Varelas13Styliani Kokkoris14Apostolia Papalexandri15Maria Fotoulaki16Assimina Galli-Tsinopoulou17Dimitrios Zafeiriou18Emmanuel Roilides19Ioanna Sakellari20Achilles Anagnostopoulos21Athanasios Tragiannidis22Hematology Department & BMT Unit, G Papanicolaou Hospital, 57010 Thessaloniki, GreeceLaboratory of Pharmacology, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceHematology Department & BMT Unit, G Papanicolaou Hospital, 57010 Thessaloniki, Greece1st Pediatric Department, Aristotle University of Thessaloniki, Hipporkation Hospital, 54642 Thessaloniki, Greece4th Pediatric Department, Aristotle University of Thessaloniki, Papageorgiou Hospital, 56429 Thessaloniki, Greece3rd Pediatric Department, Aristotle University of Thessaloniki, Hippokration Hospital, 54642 Thessaloniki, GreeceHematology Department & BMT Unit, G Papanicolaou Hospital, 57010 Thessaloniki, GreeceHematology Department & BMT Unit, G Papanicolaou Hospital, 57010 Thessaloniki, Greece3rd Pediatric Department, Aristotle University of Thessaloniki, Hippokration Hospital, 54642 Thessaloniki, Greece3rd Pediatric Department, Aristotle University of Thessaloniki, Hippokration Hospital, 54642 Thessaloniki, Greece1st Pediatric Department, Aristotle University of Thessaloniki, Hipporkation Hospital, 54642 Thessaloniki, Greece4th Pediatric Department, Aristotle University of Thessaloniki, Papageorgiou Hospital, 56429 Thessaloniki, GreeceHematology Department & BMT Unit, G Papanicolaou Hospital, 57010 Thessaloniki, GreeceHematology Department & BMT Unit, G Papanicolaou Hospital, 57010 Thessaloniki, GreeceLaboratory of Hematology and Hospital—Blood Transfusion Unit, Medical School, University General Hospital “Attikon”, NKUA, 12462 Athens, GreeceHematology Department & BMT Unit, G Papanicolaou Hospital, 57010 Thessaloniki, Greece4th Pediatric Department, Aristotle University of Thessaloniki, Papageorgiou Hospital, 56429 Thessaloniki, Greece2nd Pediatric Department, Aristotle University of Thessaloniki, AHEPA Hospital, 54621 Thessaloniki, Greece1st Pediatric Department, Aristotle University of Thessaloniki, Hipporkation Hospital, 54642 Thessaloniki, Greece3rd Pediatric Department, Aristotle University of Thessaloniki, Hippokration Hospital, 54642 Thessaloniki, GreeceHematology Department & BMT Unit, G Papanicolaou Hospital, 57010 Thessaloniki, GreeceHematology Department & BMT Unit, G Papanicolaou Hospital, 57010 Thessaloniki, Greece2nd Pediatric Department, Aristotle University of Thessaloniki, AHEPA Hospital, 54621 Thessaloniki, GreeceComplement 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 <i>C3</i>, <i>C5</i>, <i>CFB</i>, <i>CFD</i>, <i>CFH</i>, <i>CFHR1</i>, <i>CFI</i>, <i>CD46</i>, <i>CD55</i>, <i>MASP1</i>, <i>MASP2</i>, <i>MBL2</i>, <i>COLEC11</i>, <i>FCN1</i>, and <i>FCN3</i> 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 <i>CFB</i>, rs1061170, and rs1065489 <i>CFH</i> 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.https://www.mdpi.com/1467-3045/44/7/193COVID-19MIS-CchildrencomplementSNPs |
| spellingShingle | Eleni Gavriilaki Stefanos A. Tsiftsoglou Tasoula Touloumenidou Evangelia Farmaki Paraskevi Panagopoulou Elissavet Michailidou Evaggelia-Evdoxia Koravou Ioulia Mavrikou Elias Iosifidis Olga Tsiatsiou Eleni Papadimitriou Efimia Papadopoulou-Alataki Penelope Georgia Papayanni Christos Varelas Styliani Kokkoris Apostolia Papalexandri Maria Fotoulaki Assimina Galli-Tsinopoulou Dimitrios Zafeiriou Emmanuel Roilides Ioanna Sakellari Achilles Anagnostopoulos Athanasios Tragiannidis Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection Current Issues in Molecular Biology COVID-19 MIS-C children complement SNPs |
| title | Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection |
| title_full | Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection |
| title_fullStr | Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection |
| title_full_unstemmed | Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection |
| title_short | Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection |
| title_sort | targeted genotyping of mis c patients reveals a potential alternative pathway mediated complement dysregulation during covid 19 infection |
| topic | COVID-19 MIS-C children complement SNPs |
| url | https://www.mdpi.com/1467-3045/44/7/193 |
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