Alterations in immunophenotype and metabolic profile of mononuclear cells during follow up in children with multisystem inflammatory syndrome (MIS-C)

Kopitar, Andreja Nataša (author), Repas, Jernej (author), Janžič, Larisa (author), Bizjak, Maša (author), Tajnšek Vesel, Tina (author), Emeršič, Nina (author), Zajc Avramovič, Mojca (author), Ihan, Alojz (author), Avčin, Tadej (author), Pavlin, Mojca (author)

Introduction: Although children seem to be less susceptible to COVID-19, some of them develop a rare but serious hyperinflammatory condition called multisystem inflammatory syndrome in children (MIS-C). While several studies describe the clinical conditions of acute MIS-C, the status of convalescent patients in the months after acute MIS-C is still unclear, especially the question of persistence of changes in the specific subpopulations of immune cells in the convalescent phase of the disease. Methods: We therefore analyzed peripheral blood of 14 children with MIS-C at the onset of the disease (acute phase) and 2 to 6 months after disease onset (post-acute convalescent phase) for lymphocyte subsets and antigen-presenting cell (APC) phenotype. The results were compared with six healthy age-matched controls. Results: All major lymphocyte populations (B cells, CD4 + and CD8+ T cells, and NK cells) were decreased in the acute phase and normalized in the convalescent phase. T cell activation was increased in the acute phase, followed by an increased proportion of γ/δ-double-negative T cells (γ/δ DN Ts) in the convalescent phase. B cell differentiation was impaired in the acute phase with a decreased proportion of CD21 expressing, activated/memory, and class-switched memory B cells, which normalized in the convalescent phase. The proportion of plasmacytoid dendritic cells, conventional type 2 dendritic cells, and classical monocytes were decreased, while the proportion of conventional type 1 dendritic cells was increased in the acute phase. Importantly the population of plasmacytoid dendritic cells remained decreased in the convalescent phase, while other APC populations normalized. Immunometabolic analysis of peripheral blood mononuclear cells (PBMCs) in the convalescent MIS-C showed comparable mitochondrial respiration and glycolysis rates to healthy controls. Conclusions: While both immunophenotyping and immunometabolic analyzes showed that immune cells in the convalescent MIS-C phase normalized in many parameters, we found lower percentage of plasmablasts, lower expression of T cell co-receptors (CD3, CD4, and CD8), an increased percentage of γ/δ DN Ts and increased metabolic activity of CD3/CD28-stimulated T cells. Overall, the results suggest that inflammation persists for months after the onset of MIS-C, with significant alterations in some immune system parameters, which may also impair immune defense against viral infections.

• Language: English
• Keywords: MIS-C, biomarkers, metabolism, B lymphocytes, T lymphocytes, monocytes, lymphocyte activation, dendritic cells, T lymphocytes exhaustion
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine; FE - Faculty of Electrical Engineering
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 16 str.
• Numbering: Vol. 14, art. 1157702
• PID: 20.500.12556/RUL-153992
• UDC: 616-097:616-053.2
• ISSN on article: 1664-3224
• DOI: 10.3389/fimmu.2023.1157702
• COBISS.SI-ID: 151228931
• Publication date in RUL: 18.01.2024

Record is a part of a journal

• Title: Frontiers in immunology
• Shortened title: Front. immunol.
• Publisher: Frontiers Research Foundation
• ISSN: 1664-3224
• COBISS.SI-ID: 30774233

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: MIS-C, biomarkerji, metabolizem, B limfociti, T limfociti, monociti, aktivacija limfocitov, dendritske celice