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ABSTRACT
Introduction
The search for biomarkers in juvenile idiopathic arthritis (JIA) is a promising and rapidly expanding field of investigation. The biomarkers identified so far may help to dissect the clinical heterogeneity of the illness, measure the level of disease activity, predict clinical remission, relapse, response to medications, course over time, complications, and forestall disease flares.
Areas covered
We provide a summary of the most recent advances in the development and application of biomarkers in JIA. We performed a PubMed search for significant articles combining predetermined keywords related to biomarkers in non-systemic and systemic JIA, chronic uveitis, and macrophage activation syndrome (MAS). The biomarkers available or under study are presented and discussed separately for non-systemic and systemic subtypes and for the two main disease complications, uveitis and MAS.
Expert opinion
The incorporation of valid and reliable biomarkers in standard clinical care may help to design better patient-tailored treatment regimens and to improve the therapeutic strategies based on the treat-to-target approach. The establishment of biomarkers that predict the risk of disease flare may lead to define the optimal modalities for treatment discontinuation after the achievement of clinical remission.
Article highlights
The development of biomarkers is a promising and expanding area of research in juvenile idiopathic arthritis (JIA)
A number of biomarkers that may better delineate the clinical phenotype, quantify disease activity, assess medication effectiveness, or predict disease course and outcome as well as risk of disease flare or complications, especially uveitis and macrophage activation syndrome, have been developed or are under investigation
Well-established biomarkers may help to make more rational and efficacious the therapeutic strategies and minimize the risk of treatment-related adverse events
The integration of basic and clinical research in a comprehensive and innovative translational approach is required to foster the discovery of novel biomarkers and to validate those already identified
Abbreviations used in the manuscript (in alphabetical order)
| ADA: anti-drug antibody | = | |
| ADA2: adenosine deaminase 2 | = | |
| AH: aqueous humor | = | |
| AHA: anti-histones antibodies | = | |
| ANA: antinuclear antibodies | = | |
| Ang: angiopoietin | = | |
| AOSD: adult-onset Still disease | = | |
| CCL5: C-C chemokine ligand 5 | = | |
| CCP: cyclic citrullinated peptide | = | |
| cJADAS: clinical Juvenile Arthritis Disease Activity Score | = | |
| CRP: C-reactive protein | = | |
| DMARDs: disease-modifying anti-rheumatic drugs | = | |
| ELISA: enzyme-linked immunosorbent assay | = | |
| ERA: enthesitis-related arthritis | = | |
| ERAU: ERA-related uveitis | = | |
| ESR: erythrocyte sedimentation rate | = | |
| fHLH: familial hemophagocytic lymphohistiocytosis | = | |
| FMF: Familiar Mediterranean fever | = | |
| FSTL-1: Follistatin-like protein 1 | = | |
| HLA: human leukocyte antigen | = | |
| HLH: hemophagocytic lymphohistiocytosis | = | |
| HO-1: Heme oxygenase-1 | = | |
| hsCRP: high-sensitivity C-reactive protein | = | |
| IAU: idiopathic anterior uveitis | = | |
| IF: immunofluorescence | = | |
| IFN: Interferon | = | |
| IL: interleukin | = | |
| IL-18BP: IL-18-binding protein | = | |
| IL-6R: IL-6 receptor | = | |
| IL1RA: IL-1 receptor antagonist | = | |
| ILAR: International League of Associations for Rheumatology | = | |
| JADAS: Juvenile Arthritis Disease Activity Score | = | |
| JAK: Janus kinase | = | |
| JIA: juvenile idiopathic arthritis | = | |
| JIA-U: JIA-associated uveitis | = | |
| jSLE: juvenile systemic lupus erythematosus | = | |
| KD: Kawasaki disease | = | |
| MAS: macrophage activation syndrome | = | |
| mDC: myeloid dendritic cells | = | |
| MHC: histocompatibility complex | = | |
| miRNA: microRNA | = | |
| MMP: matrix metalloproteinase | = | |
| mRNA: messenger RNA | = | |
| MRP: myeloid-related protein | = | |
| MTX: methotrexate | = | |
| OR: odds ratio | = | |
| PBMC: peripheral blood mononuclear cells | = | |
| PCR: polymerase chain reaction | = | |
| PD-1: Programmed cell death 1 | = | |
| PD-1L: Programmed cell death 1 ligand | = | |
| PIU: pediatric idiopathic uveitis | = | |
| RF: rheumatoid factor | = | |
| ROC: receiver operating characteristic | = | |
| SAA: serum amyloid A | = | |
| sCD163: soluble CD163 | = | |
| sJIA: systemic juvenile idiopathic arthritis | = | |
| SNP: single nucleotide polymorphism | = | |
| sTNFR: soluble tumor necrosis factor receptor | = | |
| TGF: transforming growth factor | = | |
| Th: T helper | = | |
| TNF: tumor necrosis factor | = | |
| Tregs: regulatory T cells | = | |
| TTR: transthyretin | = | |
| VEGF: vascular endothelial growth factor | = |
Declaration of interest
The authors have non relevant affiliations or financial involvement with any organization or entity with a financial interest or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, speakers bureaus, or retainers. This paper was not funded.
Reviewers disclosure
Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.