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MRP8/14 as a Biomarker in Systemic Juvenile Idiopathic Arthritis

Jack Cush, MD

A large cohort study of children with febrile disorders has demonstrated the diagnostic utility of Myeloid-related protein 8/14 (MRP8/14) in diagnosing systemic JIA patients (SJIA) in clinical practice.

A cohort of 1110 febrile pediatric patients were divided into two cohorts: (cohort A) for validation of MRP8/14 test performance with three different testing systems: the experimental ELISA, commercial ELISA and an innovative (point-of-care test) lateral flow immunoassay (LFIA); (cohort B) to validate the diagnostic accuracy with the two latter assays.

Cohort A included 940 patients and showed significantly higher MRP8/14 levels in in SJIA (12,110 ± 2650 ng/ml) compared with others with infection or autoinflammatory disease (2980 ± 510 ng/ml) irrespective of fever and anti-inflammatory treatment (P < 0.001).  Untreated febrile patients (n = 195) with SJIA showed even higher MRP8/14 levels (19 740 ± 5080 ng/ml) compared with other diagnoses (4590 ± 1160 ng/ml) (P < 0.001, sensitivity 73%, specificity 90%).

In group B1 validation cohort, test performance was confirmed in both commercial ELISA (sensitivity 79%, specificity 89%) and LFIA (sensitivity 84%, specificity 81%) assays. Overally, MRP8/14 performance was superior to other inflammation assays, such as ferritin, IL-18, ESR, soluble IL-2 receptor and procalcitonin. 

MRP8/14 serum levels can be a rapid diagnostic point-of-care screening test to aid the diagnosis of SJIA in febrile children. 

In an accompanying editorial, the authors point out the difficulty and urgency in the diagnosis of febrile SJIA patients, often leading to diagnostic delays and delays of targeted treatments. The point out that MRP8 and MRP14 are expressed in granulocytes, monocytes and macrophages and the MRP8/14 complex is secreted via the alternative pathway. MRP8/14 binds to Toll-like receptor 4 (TLR4), eliciting pro-inflammatory effects, with a positive feedback loop with IL-1β, hence their intimacy in the pathogenesis of sJIA. Previous reports showed high MRP8/14 levels in sJIA and other inflammatory and autoinflammatory disorders (but not familial Mediterranean fever). Moreover this marker has good correlation with disease activity and relapses, suggesting its additional utility as a biomarker.  

Further research is needed to confirm these findings and to test the utility of MRP8/14 in other disorders, malignancies and clinical situations.


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