Tear‐based biomarker trajectories associated with uveitis in juvenile idiopathic arthritis: a multicenter prospective study

Background Extent of uveitis risk in juvenile idiopathic arthritis (JIA) is based on clinical factors. We aim to compare the trajectories of tear‐based biomarker levels of patients with JIA with and without uveitis. Methods This prospective multicenter study included children with JIA at risk for uveitis (JIA‐no‐U), and with JIA‐associated uveitis (JIA‐U). Serial tear samples were collected from each eye by Schirmer strips at enrollment (E) and follow‐up (FU1, FU2). S100 proteins, cytokines, and chemokines were assayed by Luminex or ELISA and compared between groups. Findings Fifty patients (37 JIA‐no‐U, 13 JIA‐U) contributed 222 samples (150 JIA‐no‐U, 73 JIA‐U). At E there were no significant differences in biomarker levels between JIA‐U and JIA‐no‐U. During follow‐up of JIA‐U, monocyte chemoattractant protein‐1 (MCP‐1) levels increased longitudinally from E to FU1 and FU2 (1.63±0.31 to 2.46±0.31, p=0.005; and 2.89±0.32, p<0.0001), similar in Chemokine (C‐X‐C motif) Ligand (CXCL)‐10 from E to FU1 and FU2 (4.39±0.41 to 5.26±0.41, p = 0.030; and 6.51±0.43, p < 0.0001) and in IL‐8 levels from E to FU1 and FU2 (3.09±0.30 to 4.25±0.30, p = 0.006; and 4.65±0.32, p ≤ 0.001). In both groups, S100A12 and S100A8/A9 increased from E to FU. Conclusion Longitudinal changes in MCP‐1, CXCL10 and IL‐8 levels in tear fluid in JIA‐U may reflect inflammatory ocular processes and support the role of monocytes and interferon related pathways in uveitis. Lack of differences in S100 proteins may reflect systemic inflammation from arthritis. Tear‐based biomarkers may support clinical factors for identifying children with JIA who develop uveitis.