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. 2022 Jul 31;14(8):1699.
doi: 10.3390/v14081699.

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

Aline Cristina Zanchettin  1   2 , Leonardo Vinicius Barbosa  1   2 , Anderson Azevedo Dutra  3 , Daniele Margarita Marani Prá  3 , Marcos Roberto Curcio Pereira  3 , Rebecca Benicio Stocco  3 , Ana Paula Camargo Martins  3 , Caroline Busatta Vaz de Paula  3 , Seigo Nagashima  3 , Lucia de Noronha  3 , Cleber Machado-Souza  1   2
Affiliations

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

Aline Cristina Zanchettin et al. Viruses. .

Abstract

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.

Keywords: SARS-CoV-2; immunohistochemistry; macrophage; polymorphisms; secondary hemophagocytic lymphohistiocytosis.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the study’s design, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Graphics are showing tissue immunoexpression of perforin (number of perforin + cells per high-power fields—HPF) for COVID-19, H1N1, and CONTROL groups. Photomicrography shows T lymphocytes (arrows) expressing perforin in all three groups (40× HPF).
Figure 2
Figure 2
Tissue immunoexpression of CD8+ and CD57+ (number of positive cells per high-power fields—HPF) for COVID-19, H1N1, and CONTROL groups in 40× HPF (arrows show immunostained cells).
See this image and copyright information in PMC

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