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Article

Role of Genetic Polymorphism Present in Macrophage Activation Syndrome Pathway in Post Mortem Biopsies of Patients with COVID-19

1
Faculdades Pequeno Príncipe, Av. Iguaçu, 333, Curitiba 80230-020, Paraná, Brazil
2
Instituto de Pesquisa Pelé Pequeno Príncipe, Av. Silva Jardim, 1632, Curitiba 80250-200, Paraná, Brazil
3
School of Medicine, Pontifícia Universidade Católica do Paraná, R. Imaculada Conceição, 1155, Curitiba 80215-901, Paraná, Brazil
*
Author to whom correspondence should be addressed.
Academic Editor: Benjamin M. Liu
Viruses 2022, 14(8), 1699; https://doi.org/10.3390/v14081699
Received: 8 June 2022 / Revised: 22 July 2022 / Accepted: 28 July 2022 / Published: 31 July 2022
(This article belongs to the Special Issue SARS-CoV-2 Innate and Adaptive Immune Responses)
COVID-19 is a viral disease associated with an intense inflammatory response. Macrophage Activation Syndrome (MAS), the complication present in secondary hemophagocytic lymphohistiocytosis (sHLH), shares many clinical aspects observed in COVID-19 patients, and investigating the cytolytic function of the responsible cells for the first line of the immune response is important. Formalin-fixed paraffin-embedded lung tissue samples obtained by post mortem necropsy were accessed for three groups (COVID-19, H1N1, and CONTROL). Polymorphisms in MAS cytolytic pathway (PRF1; STX11; STXBP2; UNC13D and GZMB) were selected and genotyping by TaqMan® assays (Thermo Fisher Scientific, MA, USA) using Real-Time PCR (Applied Biosystems, MA USA). Moreover, immunohistochemistry staining was performed with a monoclonal antibody against perforin, CD8+ and CD57+ proteins. Histopathological analysis showed high perforin tissue expression in the COVID-19 group; CD8+ was high in the H1N1 group and CD57+ in the CONTROL group. An association could be observed in two genes related to the cytolytic pathway (PRF1 rs885822 G/A and STXBP2 rs2303115 G/A). Furthermore, PRF1 rs350947132 was associated with increased immune tissue expression for perforin in the COVID-19 group. The genotype approach could help identify patients that are more susceptible, and for this reason, our results showed that perforin and SNPs in the PRF1 gene can be involved in this critical pathway in the context of COVID-19. View Full-Text
Keywords: SARS-CoV-2; secondary hemophagocytic lymphohistiocytosis; macrophage; immunohistochemistry; polymorphisms SARS-CoV-2; secondary hemophagocytic lymphohistiocytosis; macrophage; immunohistochemistry; polymorphisms
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MDPI and ACS Style

Zanchettin, A.C.; Barbosa, L.V.; Dutra, A.A.; Prá, D.M.M.; Pereira, M.R.C.; Stocco, R.B.; Martins, A.P.C.; Vaz de Paula, C.B.; Nagashima, S.; de Noronha, L.; Machado-Souza, C. Role of Genetic Polymorphism Present in Macrophage Activation Syndrome Pathway in Post Mortem Biopsies of Patients with COVID-19. Viruses 2022, 14, 1699. https://doi.org/10.3390/v14081699

AMA Style

Zanchettin AC, Barbosa LV, Dutra AA, Prá DMM, Pereira MRC, Stocco RB, Martins APC, Vaz de Paula CB, Nagashima S, de Noronha L, Machado-Souza C. Role of Genetic Polymorphism Present in Macrophage Activation Syndrome Pathway in Post Mortem Biopsies of Patients with COVID-19. Viruses. 2022; 14(8):1699. https://doi.org/10.3390/v14081699

Chicago/Turabian Style

Zanchettin, Aline Cristina, Leonardo Vinicius Barbosa, Anderson Azevedo Dutra, Daniele Margarita Marani Prá, Marcos Roberto Curcio Pereira, Rebecca Benicio Stocco, Ana Paula Camargo Martins, Caroline Busatta Vaz de Paula, Seigo Nagashima, Lucia de Noronha, and Cleber Machado-Souza. 2022. "Role of Genetic Polymorphism Present in Macrophage Activation Syndrome Pathway in Post Mortem Biopsies of Patients with COVID-19" Viruses 14, no. 8: 1699. https://doi.org/10.3390/v14081699

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