1. The role of the lectin pathway of the complement system in SARS-CoV-2 lung injury
- Author
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Marina Luise Viola de Azevedo, Ana Carolina Gadotti, Jarbas da Silva Motta-Junior, Leticia Arianne Panini do Carmo, Ana Paula Kubaski Benevides, Aline S. Fonseca, Cleber Machado-Souza, Lucia de Noronha, Rafaela Chiuco Zeni, Andrea N Moreno-Amaral, Sonia Mara Raboni, Mineia Alessandra Scaranello Malaquias, Plínio Cézar-Neto, and Ana Paula Camargo Martins
- Subjects
Male ,0301 basic medicine ,IHC, Immunohistochemistry ,medicine.disease_cause ,Influenza A Virus, H1N1 Subtype ,0302 clinical medicine ,Lectins ,Influenza A virus ,Complement Activation ,Lung ,Aged, 80 and over ,biology ,H&E, Hematoxylin and Eosin ,Lung Injury ,General Medicine ,Middle Aged ,Immunohistochemistry ,030220 oncology & carcinogenesis ,Lectin pathway ,Cytokines ,Original Article ,Female ,Autopsy ,Antibody ,rRT-PCR, Reverse Transcriptase-Polymerase Chain Reaction ,Adult ,DAD, Diffuse Alveolar Damage ,Genotype ,Lung injury ,ACE-2, Angiotensin-Convertase-Enzyme-2 Receptors ,FFPE, Formalin-Fixed Paraffin-Embedded ,MBL, Mannose-Binding Lectin ,Polymorphism, Single Nucleotide ,Proinflammatory cytokine ,Young Adult ,03 medical and health sciences ,Physiology (medical) ,Influenza, Human ,medicine ,Humans ,Aged ,Biochemistry, medical ,HPF, High-Power Field ,SARS-CoV-2 ,Biochemistry (medical) ,Public Health, Environmental and Occupational Health ,COVID-19 ,Complement system ,030104 developmental biology ,H1N1pdm09, Pandemic Influenza A Virus H1N1 Subtype Infection ,Case-Control Studies ,Immunology ,biology.protein ,CD163 - Abstract
Although some evidence showed the activation of complement systems in COVID-19 patients, proinflammatory status and lectin pathway remain unclear. Thus, the present study aimed to demonstrate the role of MBL and ficolin-3 in the complement system activation and compared to pandemic Influenza A virus H1N1 subtype infection (H1N1pdm09) and control patients. A total of 27 lungs formalin-fixed paraffin-embedded samples (10 from H1N1 group, 6 from the COVID-19 group, and 11 from the control group) were analyzed by immunohistochemistry using anti-IL-6, TNF-alfa, CD163, MBL e FCN3 antibodies. Genotyping of target polymorphisms in the MBL2 gene was performed by real-time PCR. Proinflammatory cytokines such as IL-6 and TNF-alpha presented higher tissue expression in the COVID-19 group compared to H1N1 and control groups. The same results were observed for ICAM-1 tissue expression. Increased expression of the FCN3 was observed in the COVID-19 group and H1N1 group compared to the control group. The MBL tissue expression was higher in the COVID-19 group compared to H1N1 and control groups. The genotypes AA for rs180040 (G/A), GG for rs1800451 (G/A) and CC for rs5030737 (T/C) showed a higher prevalence in the COVID-19 group. The intense activation of the lectin pathway, with particular emphasis on the MBL pathway, together with endothelial dysfunction and a massive proinflammatory cytokines production, possibly lead to a worse outcome in patients infected with SARS-Cov-2. Moreover, 3 SNPs of our study presented genotypes that might be correlated with high MBL tissue expression in the COVID-19 pulmonary samples.
- Published
- 2021