MRP8/14 serum levels as diagnostic markers for systemic juvenile idiopathic arthritis in children with prolonged fever

Abstract

Objectives Differential diagnosis in children with prolonged fever is challenging. In particular, differentiating systemic-onset juvenile idiopathic arthritis (SJIA) from infectious diseases is difficult. Biomarkers are needed supporting the diagnostic work-up. The aim of this study was to validate the usefulness of MRP8/14 measurements in the diagnostic wok-up of febrile children and transfer it to clinical practice. Methods Data of 1,110 paediatric patients were included and divided into two cohorts: (A) For validation of MRP8/14 test performance with 3 different testing systems: the experimental enzyme-linked immunosorbent sandwich assay (ELISA), commercial ELISA and an innovative (POCT) lateral flow immunoassay (LFIA); (B) to validate the diagnostic accuracy with the two latter assays. Results In cohort A (n = 940), MRP8/14 was elevated in SJIA (12110±2650 ng/ml mean ± 95% CI) compared to other diagnoses (including infections and autoinflammatory diseases; 2980±510 ng/ml) irrespective of fever and anti-inflammatory treatment (p < 0.001). In untreated patients with fever (n = 195) MRP8/14 levels in SJIA (19740±5080 ng/ml) were even higher compared to other diagnoses (4590±1160 ng/ml) (p < 0.001, sensitivity 73%, specificity 90%). In cohort B1, the performance of the tests was confirmed in untreated patients with fever (n = 170): commercial ELISA (sensitivity 79%, specificity 89%) and LFIA (sensitivity 84%, specificity 81%). Compared with ferritin, IL-18, ESR, sIL2-R, and procalcitonin, MRP8/14 showed the best accuracy. Conclusion MRP8/14 serum analyses have been validated as a helpful tool supporting the diagnosis of SJIA in febrile children. The results could be confirmed with commercial ELISA and LFIA enabling a rapid diagnostic point-of-care screening test.

Aberrant naive CD4+ T Cell differentiation in systemic juvenile idiopathic arthritis is committed to B cell help

“…Patients diagnosed with macrophage activation syndrome (MAS) met the 2016 classification criteria for MAS complicating sJIA(37, 38). Serum samples were collected from sJIA patients (n=34; active disease (AD), n = 25; inactive disease (ID), n = 9) and pediatric HCs (n = 10) in course of a larger study as recently reported by us(39). Collective demographic and clinical characteristics are summarized in Table 1 .…”

Biomarkers in Systemic Juvenile Idiopathic Arthritis, Macrophage Activation Syndrome and Their Importance in COVID Era

“…The absence of arthritis at the beginning of the disease is an impediment for clinicians, as there are currently no reliable diagnostic criteria, and this could lead to a delay in early positive diagnosis, which may have consequences for the initiation of targeted treatment, as well as patients’ outcomes and prognosis [ 17 , 18 ].…”

“…In children and adolescents with fever, but without treatment ( n = 195), serum concentrations of MRP8/14 in sJIA (19740 ± 5080 ng/mL) were much higher compared to other diagnoses, having the highest precision compared to all other parameters measured—such as ferritin, IL-18, ESR, soluble IL-2 receptor, and procalcitonin. The authors highlighted that serum tests of MRP8/14 can be useful for the positive diagnosis of sJIA in febrile patients, and commercial ELISA and LFIA allow accurate testing for rapid diagnostic screening at the point of care [ 18 ].…”

“…Serum concentrations of MRP8/14 have been confirmed as an important biomarker for the diagnosis of sJIA, ensuring early discrimination from other inflammatory conditions so that targeted therapy for the patient’s benefit can be started immediately when the “window of opportunity” is open, stopping a possible persistent chronic outcome which, until the discovery of bDMARDs, was inevitable in more than 50% of patients [ 17 , 18 , 58 , 153 ].…”

Identification of Potential Diagnostic Biomarkers for Systemic Juvenile Idiopathic Arthritis by Integrative Transcriptomic Analysis

“…Accumulating biomarkers have been reported as potential biomarkers including but not limited to heme oxygenase-1, interleukin-6 (IL-6), IL-12, IL-18, osteoprotegerin, S100 calcium-binding protein A12 (S100A12) and S100A8/A9, among which only S100A8 and S100A9 were recently validated in a large cohort study of 1110 febrile pediatric patients and proposed to be the most promising biomarkers for sJIA diagnosis [7,8]. S100A8/9, with a cut off at 9160ng/ml, showed a 73% sensitivity and a 90% speci city in differentiating sJIA in fever of unknown origin among 195 untreated febrile pediatric patients.…”