Comparison of biomarkers for systemic juvenile idiopathic arthritis

Abstract

Background: Differentiation of systemic juvenile idiopathic arthritis (SJIA) fever from other childhood fevers is often delayed due to the lack of reliable, specific biomarkers. We hypothesized that PD-L1 expression is dysregulated in SJIA monocytes and compared it to other candidate SJIA biomarkers. Methods: This pilot study enrolled children with fever without source and compared PD-L1 expression on myeloid cells to C-reactive protein, erythrocyte sedimentation rate, leukocyte counts, S100A12, S100A8, S100A9, calprotectin, and procalcitonin. Logistic regression models were fit to test SJIA diagnosis with each marker used as an independent predictor. Receiver operating characteristic curves and area under curve were calculated. Gene expression profiling on a subset of samples was performed. results: Twenty subjects (10 active SJIA, 10 febrile non-SJIA) were enrolled. S100 proteins were significantly elevated in SJIA with >80% sensitivity and >90% specificity. PD-L1 expression was significantly lower in SJIA. Other markers were not specific for SJIA. On exploratory gene analysis, 106 genes were significant for SJIA association, and several of these are associated with immune response pathways. conclusion: In this small cohort, S100 proteins were specific diagnostic biomarkers for SJIA in children with fever. Decreased PD-L1 surface expression on circulating myeloid cells in SJIA suggests possible mechanism for loss of peripheral immune regulation.

Measurement of blood calprotectin (MRP-8/MRP-14) levels in patients with juvenile idiopathic arthritis

“…In patients with sJIA the median calprotectin level was 13,800 ng/ml, while in patients with the non-systemic disease type it was 2,700 ng/ml. Similar results were obtained in the study by Shenoi et al (2014), where the median level of calprotectin in patients with systemic-onset JIA was 38,600 ng/ml, and in patients with a non-systemic disease course it was 4,700 ng/ml [11]. …”

“…The higher levels of calprotectin in patients involved in the Stanford University study can be explained by the fact that the majority of patients with sJIA had newly diagnosed disease [11]. In the study conducted at our clinic the highest calprotectin level was found in children with newly diagnosed sJIA (median 32,500 ng/ml, range: 13,800–177,000 ng/ml) (Fig.…”

S100A8/A9, a potent serum and molecular imaging biomarker for synovial inflammation and joint destruction in seronegative experimental arthritis

“…The search for more reliable biomarkers for seronegative arthritis has resulted in several serum proteins that are associated with disease activity in patients with seronegative arthritis: IL-6, IL-17, IL-23, VEGF, and MMP3 in SpA [6, 7, 40–43], and IL-6 and IL-18 in JIA [5, 36, 44], amongst others. Although these proteins correlate with certain clinical aspects of seronegative arthritis, a major problem remains the lack of specificity, and results are often inconsistent; moreover, these putative biomarkers still await validation in cohort studies.…”

Діагностичне Та Прогностичне Значення Кальпротектину (MRP8/MRP14) У Крові Хворих На Різні Варіанти Ювенільного Ідіопатичного Артриту

“…У хворих на сЮІА медіана рівня кальпротектину становила 13 800 нг/мл, а у пацієнтів із не-системним перебігом -2700 нг/мл. Подібні результати отримані у дослідженні Susan Shenoi (2014), де медіана кальпротектину у хворих на системний ЮІА становила 38 600 мкг/мл, а у пацієнтів із несистемним перебігом -4700 нг/мл [10]. Вищі рівні кальпротектину у хворих, залучених у дослідження Стенфордського університету, пояснюються тим, що у більшості хворих на сЮІА захворювання було діагностовано вперше.…”