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. 2022 Jul 6;61(7):3082-3092.
doi: 10.1093/rheumatology/keab729.

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

Carolin Park  1 , María Miranda-Garcia  1 , Rainer Berendes  2 , Gerd Horneff  3 , Jasmin Kuemmerle-Deschner  4 , Gerd Ganser  5 , Hans-Iko Huppertz  6 , Kirsten Minden  7 , Johannes-Peter Haas  8 , Annette F Jansson  9 , Michael Borte  10 , Catharina Schuetz  11 , Prasad Oommen  12 , Michael Frosch  13 , Bernhard Schlueter  14 , Annette Richter-Unruh  15 , Christoph Kessel  1 , Claas Hinze  1 , Helmut Wittkowski  1 , Johannes Roth  16 , Dirk Foell  1 , Dirk Holzinger  17
Affiliations

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

Carolin Park et al. Rheumatology (Oxford). .

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.

Keywords: MRP8/14; autoinflammation; biomarker; diagnosis; fever; infection; point-of-care test; validation.

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