Gavriilaki Eleni, Tsiftsoglou Stefanos A, Touloumenidou Tasoula, Farmaki Evangelia, Panagopoulou Paraskevi, Michailidou Elissavet, Koravou Evaggelia-Evdoxia, Mavrikou Ioulia, Iosifidis Elias, Tsiatsiou Olga, Papadimitriou Eleni, Papadopoulou-Alataki Efimia, Papayanni Penelope Georgia, Varelas Christos, Kokkoris Styliani, Papalexandri Apostolia, Fotoulaki Maria, Galli-Tsinopoulou Assimina, Zafeiriou Dimitrios, Roilides Emmanuel, Sakellari Ioanna, Anagnostopoulos Achilles, Tragiannidis Athanasios
Hematology Department & BMT Unit, G Papanicolaou Hospital, 57010 Thessaloniki, Greece.
Laboratory of Pharmacology, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Curr Issues Mol Biol. 2022 Jun 28;44(7):2811-2824. doi: 10.3390/cimb44070193.
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.
补体失调在患有新冠肺炎的成年人中已有记录，并与针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的相关儿科炎症反应有关。我们提出，在患有多系统炎症综合征（MIS-C）的儿童中也可以识别出与失调相关的补体错义编码单核苷酸多态性（SNP）特征。我们调查了在2020年11月至2021年3月期间在三个主要组别的儿科新冠肺炎护理病房住院的71例经逆转录聚合酶链反应（RT-PCR）验证感染SARS-CoV-2的儿科患者。7例患者患有MIS-C（MIS-C组），32例患有新冠肺炎并住院（入院组），而32例患有新冠肺炎但被送回家。所有患者均存活，并对其、、、、、、、、、、、、、、和基因的变异进行了基因分型。在评估三个研究组中错义编码SNP的分布模式时，我们注意到了相似之处，但也发现MIS-C患者中与SNP rs12614、rs1061170和rs1065489相关的替代途径（AP）频率显著增加。我们的分析表明，相应的替代可能会降低C3b失活效率，并促进病毒粒子上AP C3bBb前转换酶的组装更慢且更弱。在这种情况下，补体AP调理作用能力可能受损，导致MIS-C综合征中的免疫清除受损和全身炎症。
