RNAseq-based transcriptomics of treatment-naïve multi-inflammatory syndrome in children (MIS-C) demonstrates predominant activation of matrisome, innate and humoral immune pathways.

Autor: Patnaik S; Department of Paediatrics, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, India., Mruthyunjaya P; Department of Clinical Immunology and Rheumatology, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, 751024, India., Murmu KC; Chromatin and Epigenetics Unit, Institute of Life Sciences, Bhubaneswar, India., Mahapatra S; Chromatin and Epigenetics Unit, Institute of Life Sciences, Bhubaneswar, India., Patro ARK; Department of Biochemistry and Molecular Diagnostics, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, India., Misra R; Department of Clinical Immunology and Rheumatology, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, 751024, India., Pati S; Director of Public Health, ICMR-RMRC, Bhubaneswar, India., Prasad P; Chromatin and Epigenetics Unit, Institute of Life Sciences, Bhubaneswar, India. punit@ils.res.in., Ahmed S; Department of Clinical Immunology and Rheumatology, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, 751024, India. sakir005@gmail.com.
Jazyk: angličtina
Zdroj: Rheumatology international [Rheumatol Int] 2024 Aug; Vol. 44 (8), pp. 1445-1454. Date of Electronic Publication: 2023 Oct 12.
DOI: 10.1007/s00296-023-05478-0
Abstrakt: MIS-C is a rare, highly inflammatory state resembling incomplete Kawasaki disease, temporarily associated with COVID-19. The pathogenesis is not completely known. RNAseq was carried out on whole blood of six treatment-naïve MIS-C patients. This was compared against RNAseq transcriptomics data of five healthy controls (HC), four Kawasaki Disease (KD) and seven systemic Juvenile Idiopathic Arthritis (sJIA). Using PCA, MIS-C clustered separately from HC, KD and sJIA. Amongst the top 50 significant genes in the three comparisons with HC, KD, and sJIA, common genes were: TMCC2, ITGA2B, DMTN, GFI1B, PF4, QSER1, GRAP2, TUBB1. DSEA revealed that maximum number of hits for overexpressed pathways was for NABA matrisome activation when MIS-C was compared against HC. Cytokine stimulated cellular activation pathways, specifically IL-10 were downregulated. MIS-C had more activated pathways of neutrophil degranulation and acquired immune activation but less of coagulation system or heat-shock system involvement as compared to KD. As compared to sJIA, humoral immune response and complements were activated. Matrisome activation was higher, with increased cell-cell interaction and ECM signalling. This analysis revealed novel insights into the pathogenesis of MIS-C, including the potential role of matrisomes, humoral immune system and down-regulated interleukin-10 pathways.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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