ArticleArthritis & rheumatology (Hoboken, N.J.)2022
Identification of Distinct Inflammatory Programs and Biomarkers in Systemic Juvenile Idiopathic Arthritis and Related Lung Disease by Serum Proteome Analysis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- EULAR/PReS recommendations for the diagnosis and management of Still's disease, comprising systemic juvenile idiopathic arthritis and adult-onset Still's disease.Annals of the rheumatic diseases · 2024Guideline
- Advancements in Diagnosis and Care for Immune Dysregulation and Inborn Errors of Immunity in Pediatric Rheumatology: Our 50-Year Journey.Arthritis care & research · 2026Review
- Baseline Clinical Features and Biomarker Profiles of the Childhood Arthritis and Rheumatology Research Alliance Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease Cohort.Arthritis care & research · 2026Article
- Distinct cytokine and chemokine alterations in bronchoalveolar fluid from patients with systemic juvenile idiopathic arthritis associated lung disease (SJIA-LD).Arthritis research & therapy · 2026Article
- Efficacy of combined JAK1/2 inhibition and cyclosporine in paediatric-onset Still's disease with lung involvement: a case report.Pediatric rheumatology online journal · 2026Article
- Enterovirus D68 receptor usage: from static attachment to dynamic entry.Journal of virology · 2026Review
- Decoding pulmonary risk in childhood-onset still's disease: immunogenetic determinants and implications for risk stratification.Respiratory research · 2026Article
- Exploring new drug treatment targets for immune related bone diseases using a multi omics joint analysis strategy.Scientific reports · 2025Article
- 3D clustering of gene expression data from systemic autoinflammatory diseases using self-organizing maps (Clust3D).Computational and structural biotechnology journal · 2024Article
- Interleukin (IL)-1/IL-6-Inhibitor-Associated Drug Reaction With Eosinophilia and Systemic Symptoms (DReSS) in Systemic Inflammatory Illnesses.The journal of allergy and clinical immunology. In practice · 2024Article
- Hyperferritinemia Screening to Aid Identification and Differentiation of Patients with Hyperinflammatory Disorders.Journal of clinical immunology · 2024Article
- A Narrative Review of the IL-18 and IL-37 Implications in the Pathogenesis of Atopic Dermatitis and Psoriasis: Prospective Treatment Targets.International journal of molecular sciences · 2024Review
- sMR and PTX3 levels associate with COVID-19 outcome and survival but not with Long COVID.iScience · 2024Article
- Initial Respiratory System Involvement in Juvenile Idiopathic Arthritis with Systemic Onset Is a Marker of Interstitial Lung Disease: The Results of Retrospective Cohort Study Analysis.Journal of clinical medicine · 2024Article
- Hyperferritinemia screening to aid identification and differentiation of patients with hyperinflammatory disorders.Research square · 2024Article
- Single-cell RNA sequencing in juvenile idiopathic arthritis.Genes & diseases · 2024Review
- Disease Course, Treatments, and Outcomes of Children With Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease.Arthritis care & research · 2024Article
- Recent advances and evolving concepts in Still's disease.Nature reviews. Rheumatology · 2024Review
- Elevation of IL-17 Cytokines Distinguishes Kawasaki Disease From Other Pediatric Inflammatory Disorders.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- The 4Pediatric rheumatology online journal · 2024Article
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 1 country.
Funding
Abstract
objectiveRecent observations in systemic juvenile idiopathic arthritis (JIA) suggest an increasing incidence of high-mortality interstitial lung disease often characterized by a variant of pulmonary alveolar proteinosis (PAP). Co-occurrence of macrophage activation syndrome (MAS) and PAP in systemic JIA suggests a shared pathology, but patients with lung disease associated with systemic JIA (designated SJIA-LD) also commonly experience features of drug reaction such as atypical rashes and eosinophilia. This study was undertaken to investigate immunopathology and identify biomarkers in systemic JIA, MAS, and SJIA-LD.
methodsWe used SOMAscan to measure ~1,300 analytes in sera from healthy controls and patients with systemic JIA, MAS, SJIA-LD, or other related diseases. We verified selected findings by enzyme-linked immunosorbent assay and lung immunostaining. Because the proteome of a sample may reflect multiple states (systemic JIA, MAS, or SJIA-LD), we used regression modeling to identify subsets of altered proteins associated with each state. We tested key findings in a validation cohort.
resultsProteome alterations in active systemic JIA and MAS overlapped substantially, including known systemic JIA biomarkers such as serum amyloid A and S100A9, and novel elevations in the levels of heat-shock proteins and glycolytic enzymes. Interleukin-18 levels were elevated in all systemic JIA groups, particularly MAS and SJIA-LD. We also identified an MAS-independent SJIA-LD signature notable for elevated levels of intercellular adhesion molecule 5 (ICAM-5), matrix metalloproteinase 7 (MMP-7), and allergic/eosinophilic chemokines, which have been previously associated with lung damage. Immunohistochemistry localized ICAM-5 and MMP-7 in the lungs of patients with SJIA-LD. The ability of ICAM-5 to distinguish SJIA-LD from systemic JIA/MAS was independently validated.
conclusionSerum proteins support a systemic JIA-to-MAS continuum; help distinguish systemic JIA, systemic JIA/MAS, and SJIA-LD; and suggest etiologic hypotheses. Select biomarkers, such as ICAM-5, could aid in early detection and management of SJIA-LD.
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