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

Sibabratta Patnaik; Prakashini Mruthyunjaya; Krushna Chandra Murmu; Soumendu Mahapatra; A Raj Kumar Patro; Ramnath Misra; Sanghamitra Pati; Punit Prasad; Sakir Ahmed

doi:10.1007/s00296-023-05478-0

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

Rheumatol Int. 2023 Oct 12. doi: 10.1007/s00296-023-05478-0. Online ahead of print.

Authors

Sibabratta Patnaik¹, Prakashini Mruthyunjaya², Krushna Chandra Murmu³, Soumendu Mahapatra³, A Raj Kumar Patro⁴, Ramnath Misra², Sanghamitra Pati⁵, Punit Prasad⁶, Sakir Ahmed⁷

Affiliations

¹ Department of Paediatrics, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, India.
² Department of Clinical Immunology and Rheumatology, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, 751024, India.
³ Chromatin and Epigenetics Unit, Institute of Life Sciences, Bhubaneswar, India.
⁴ Department of Biochemistry and Molecular Diagnostics, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, India.
⁵ Director of Public Health, ICMR-RMRC, Bhubaneswar, India.
⁶ Chromatin and Epigenetics Unit, Institute of Life Sciences, Bhubaneswar, India. punit@ils.res.in.
⁷ Department of Clinical Immunology and Rheumatology, Kalinga Institute of Medical Sciences, KIIT University, Bhubaneswar, 751024, India. sakir005@gmail.com.

PMID: 37823896
DOI: 10.1007/s00296-023-05478-0

Abstract

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.

Keywords: COVID-19; MIS-C; Matrisome; Next-generation sequencing; Transcriptomics.