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Park, Carolin; Miranda-Garcia, Maria; Berendes, Rainer; Horneff, Gerd; Kümmerle-Deschner, Jasmin; Ganser, Gerd; Huppertz, Hans-Iko; Minden, Kirsten; Haas, Johannes-Peter; Jansson, Annette F.; Borte, Michael; Schütz, Catharina; Oommen, Prasad; Frosch, Michael; Schlüter, Bernhard; Richter-Unruh, Annette; Kessel, Christoph; Hinze, Claas; Wittkowski, Helmut; Roth, Johannes; Föll, Dirk und Holzinger, Dirk (2022): MRP8/14 serum levels as diagnostic markers for systemic juvenile idiopathic arthritis in children with prolonged fever. In: Rheumatology, Bd. 61, Nr. 7: S. 3082-3092

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Abstract

Objectives Differential diagnosis in children with prolonged fever is challenging. In particular, differentiating systemic-onset JIA (SJIA) from infectious diseases is difficult. Biomarkers are needed that support the diagnostic work-up. The aim of this study was to validate the usefulness of Myeloid-related protein 8/14 (MRP8/14) measurements in the diagnostic work-up of febrile children and to transfer it to clinical practice. Methods Data for 1110 paediatric patients were included and 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. Results In cohort A (n = 940), MRP8/14 was elevated in SJIA (12 110 +/- 2650 ng/ml mean +/- 95% CI) compared with 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 (19 740 +/- 5080 ng/ml) were even higher compared with other diagnoses (4590 +/- 1160 ng/ml) (P < 0.001, sensitivity 73%, specificity 90%). In group 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, soluble IL-2 receptor 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.

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