Intraocular Biomarker Identification in Uveitis Associated With Juvenile Idiopathic Arthritis

Abstract

PURPOSE.To investigate the presence of biomarkers in aqueous humor (AH) from patients with uveitis associated with juvenile idiopathic arthritis (JIA).METHODS. AH (n ¼ 73) and serum (n ¼ 105) samples from 116 children were analyzed using surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-ToF MS). The samples were divided into the following groups: JIA, silent chronic anterior uveitis (AU), other uveitis entities, and noninflammatory controls. Statistical biomarker identification was performed using the SELDI-ToF Biomarker Analysis Cluster Wizard followed by multivariate statistical analysis. Biochemical identification of biomarkers was performed by polyacrylamide gel protein separation, followed by liquid chromatography tandem mass spectrometry. ELISA was performed in a number of AH samples representing all four study groups.RESULTS. In the JIA group, one AH protein peak at mass/charge (m/z) 13,762 had qualitative and quantitative differences in expression compared with the other uveitis entities and the controls, but not to the group of silent chronic AU. Its quantitative expression in AH of patients with JIA and other silent chronic AU was positively associated with uveitis activity. The protein at m/z 13,762 in AH was identified as transthyretin (TTR). The TTR concentration in AH differed significantly between the study groups (P ¼ 0.006) with considerably higher TTR concentrations in JIA and silent chronic AU samples positive for m/z 13,762 than those of the other uveitis and control groups.CONCLUSIONS. TTR is a potential intraocular biomarker of JIA-associated uveitis. Its role in the pathogenesis of silent chronic AU with and without arthritis needs further investigation.

Uveitis associated with juvenile idiopathic arthritis

“…96 In the JIA group, a protein later identified as trans thyretin was expressed at a significantly higher level than in individuals with other forms of uveitis and controls. The exact role of transthyretin in JIA-associated uveitis, and whether it is involved in the pathogenesis of this disorder, is unclear.…”

“…96 Researchers obtained aqueous humour samples from 17 patients with JIAassociated uveitis, 39 with other forms of uveitis and 20 113,114 Abbreviations: CTLA-4, cytotoxic T-lymphocyte-associated antigen 4; mAb, monoclonal antibody; RCT, randomized controlled trial.…”

Managing juvenile idiopathic arthritis–associated uveitis

“…41 Similarly, it has been also reported higher levels of transthyretin are present in the aqueous of patients with JIA-associated uveitis and silent chronic anterior uveitis compared to those of the other uveitis types and control groups. 42 Recently, a study has shown an association between parvovirus B19 and JIAassociated uveitis. In this study an intraocular antibody production against parvovirus B19 was found by Goldmann-Witmer coefficient in 7 of 13 patients with JIA-associated uveitis and only 3 of 45 patients with anterior uveitis of undetermined origin.…”

The Value of Measuring Urinary β2-Microglobulin and Serum Creatinine for Detecting Tubulointerstitial Nephritis and Uveitis Syndrome in Young Patients With Uveitis

“…Two of the 11 patients with uveitis, elevated urinary β2M, and no other signs of AIN were diagnosed as having another clinical entity including herpes simplex virus infection (confirmed by an aqueous humor analysis) and ANA-positive chronic anterior uveitis with no signs of arthritis. 12,13 The conditions of the other 9 patients remained undiagnosed despite comprehensive additional testing. Next, we calculated the predictive value of the specific tests with respect to detecting definitive and/or probable TINU syndrome.…”