Altered molecular pathways and prognostic markers in active systemic juvenile idiopathic arthritis: integrated bioinformatic analysis

Yi Ren; Hannah Labinsky; Andriko  Palmowski; Henrik Bäcker; Michael Müller; Arne Kienzle

doi:10.17305/bjbms.2021.6016

Authors

Yi Ren Center for Musculoskeletal Surgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany https://orcid.org/0000-0003-3317-7593
Hannah Labinsky Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, Germany https://orcid.org/0000-0001-5762-9182
Andriko Palmowski Department of Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany https://orcid.org/0000-0002-3456-0597
Henrik Bäcker Center for Musculoskeletal Surgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany https://orcid.org/0000-0002-4265-477X
Michael Müller Center for Musculoskeletal Surgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany https://orcid.org/0000-0002-8934-9676
Arne Kienzle Center for Musculoskeletal Surgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Laboratory of Adaptive and Regenerative Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston MA, USA https://orcid.org/0000-0002-4556-2993

DOI:

https://doi.org/10.17305/bjbms.2021.6016

Keywords:

Systemic juvenile idiopathic arthritis, hub genes, neutrophil, prognostic marker

Abstract

Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood-onset inflammatory disease characterized by arthritis accompanied by systemic auto-inflammation and extra-articular symptoms. While recent advances have unraveled a range of risk factors, the pathomechanisms involved in SJIA and potential prognostic markers for treatment success remain partly unknown. In this study, we included 70 active SJIA and 55 healthy control patients from the National Center for Biotechnology Information to analyze for differentially expressed genes (DEGs) using R. Functional enrichment analysis, protein-protein interaction (PPI), and gene module construction were performed for DEGs and hub gene set. We additionally examined immune system cell composition with CIBERSORT and predicted prognostic markers and potential treatment drugs for SJIA. In total, 94 upregulated and 24 downregulated DEGs were identified. Two specific modules of interest and eight hub genes (ARG1, DEFA4, HP, MMP8, MMP9, MPO, OLFM4, PGLYRP1) were screened out. Functional enrichment analysis suggested that complex neutrophil-related functions play a decisive role in the disease pathogenesis. CIBERSORT indicated neutrophils, M0 macrophages, CD8+ T cells, and naïve B cells to be relevant drivers of disease progression. Additionally, we identified TPM2 and GZMB as potential prognostic markers for treatment response to canakinumab. Moreover, sulindac sulfide, (-)-catechin, and phenanthridinone were identified as promising treatment agents. This study provides a new insight into molecular and cellular pathogenesis of active SJIA and highlights potential targets for further research.