Comparison of biomarkers for systemic juvenile idiopathic arthritis.
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.


CONCLUSIONS
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.
Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, Washington.|Division of Rheumatology, Department of Pediatrics, University of Washington, Seattle, Washington.
Susan
S
Shenoi
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington.
Jing-Ni
JN
Ou
Genomics Core, Systems Immunology, Benaroya Research Institute at Virginia Mason, Seattle, Washington.
Chester
C
Ni
Division of Human Gene Therapy, Program in Immunology, Stanford University, Stanford, California.
Claudia
C
Macaubas
Genomics Core, Systems Immunology, Benaroya Research Institute at Virginia Mason, Seattle, Washington.
Vivian H
VH
Gersuk
Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, Washington.|Division of Rheumatology, Department of Pediatrics, University of Washington, Seattle, Washington.
Carol A
CA
Wallace
Division of Human Gene Therapy, Program in Immunology, Stanford University, Stanford, California.
Elizabeth D
ED
Mellins
Division of Rheumatology, Department of Pediatrics, University of Washington, Seattle, Washington.|Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington.
Anne M
AM
Stevens
D019540:Area Under Curve; D001171:Arthritis, Juvenile / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D060890:B7-H1 Antigen / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D008297:Male; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D009418:S100 Proteins / Q000097:blood*
D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; D009418:S100 Proteins