Male Gender as a Risk Factor for Complications in Uveitis Associated With Juvenile Idiopathic Arthritis

Ayuso, Viera Kalinina; Cate, Hermine Adriana Theodore ten; Does, Patricia van der; Rothová, Aniki; Boer, Joke H. de

doi:10.1016/j.ajo.2010.01.016

Cited by 63 publications

(45 citation statements)

References 16 publications

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“…[43][44][45] It is, hence, perhaps surprising to find that if boys do develop uveitis their prognosis is worse than that of the girls. 17,22,39,40 Edelsten et al had 25% boys in their cohort and found the male sex was independently associated with higher complication rate (p = 0.032) and this rate was higher in the first 4 years when compared to the girls who had only a 5% complication rate and a 54% rate of remsission. 22 Chia et al found the proportion of boys with severe disease at presentation was significantly higher at 66% (9/13) compared with 33% (3/9) of girls.…”

Section: Male Gendermentioning

confidence: 87%

Juvenile Idiopathic Arthritis-Associated Uveitis: Clinical Features and Complications, Risk Factors for Severe Course, and Visual Outcome

Vitale

Graham

Boer

2013

Ocular Immunology and Inflammation

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Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease and the most prevalent systemic disorder in children with uveitis. The risk of developing uveitis is the greatest among patients with oligoarticular onset of disease. Clinical features of JIA-associated uveitis (JIAU) are nongranulomatous inflammation, anterior in location, insidious at onset, chronic course, and frequently asymptomatic in the absence of ocular structural complications. Uveitis in JIA can worsen over time with many sight-threatening complications, such as band keratopathy in the visual axis, posterior synechiae, cataract, secondary glaucoma, macular edema, hypotony, epiretinal membrane, and optic nerve edema. Different studies have pointed out that several factors are associated with poor prognosis, including young age at onset, male gender, short interval between diagnosis of arthritis and uveitis, severity of uveitis at onset, and antinuclear antibody (ANA) positivity. Although JIA associated-uveitis is still a serious blinding disease, we are at least able to identify the high-risk group.

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Section: Male Gendermentioning

confidence: 87%

Juvenile Idiopathic Arthritis-Associated Uveitis: Clinical Features and Complications, Risk Factors for Severe Course, and Visual Outcome

Vitale

Graham

Boer

2013

Ocular Immunology and Inflammation

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“…Panuveits is a rare but a possible clinical manifestation of uveitis in JIA. 3 In this study, TTR was identified as a potential biomarker for silent chronic AU, characteristic of JIA-associated uveitis. The nascent protein has a molecular weight of 15.88 kDa.…”

Section: Discussionmentioning

confidence: 99%

“…In our previous work, we have described a relatively high percentage of patients who have an atypical manifestation of JIA: with uveitis onset primary to arthritis. 2,3 The diagnosis of JIA in these patients was, in some cases, made several years after the initial onset of uveitis. Our results demonstrate similar protein compositions in the AH of patients with JIA-associated uveitis and in patients with silent chronic AU, characteristic for JIA-associated uveitis, but lacking the typical rheumatologic signs.…”

Section: Discussionmentioning

confidence: 99%

“…However, in 23% of children, uveitis can be the first sign of JIA with arthritis being diagnosed months to years after the diagnosis of uveitis. 2,3 Keeping in mind this atypical presentation of JIA and the absence of a definitive diagnostic test, there is a strong rationale for efforts to identify specific biomarkers in the ocular fluid of children with JIA-associated uveitis. Proteomic techniques based on mass spectrometry approaches are nowadays being widely applied in autoimmune diseases for the identification of biomarkers, which could serve for diagnostic, prognostic, or even therapeutic purposes.…”

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confidence: 99%

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Intraocular Biomarker Identification in Uveitis Associated With Juvenile Idiopathic Arthritis

Ayuso

Boer

Byers

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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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.

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“…Среди факторов риска тяжелого течения увеита и развития осложнений, кроме раннего дебюта и ко-роткого лага между появлением артрита и увеита, можно отметить мужской пол и наличие синехий при первом офтальмологическом осмотре [5,16,23,46].…”

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Proteomic Profile of Tears for the Diagnosis of Uveitis Associated with Juvenile Idiopathic Arthritis: Setting Targets to Achieve Results

et al. 2017

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The paper presents epidemiologic and pathophysiological aspects of the problem statement for early recognition of Uveitis (Uv) associated with Juvenile Idiopathic Arthritis (JIA) in terms of the proteomic profile of tears as well as the results of an attempt to solve this problem by means of the Tandem Mass-Spectrometry (TMS). The solution of this problem is of the highest relevance due to revolutionary changes in treatment strategies after introducing highly effective biologics. Content analysis of literature reviews reveals the following: 1. the incidence of JIA-Uv in the Northwest Federal District of Russian Federation averages 0.5-0.7 per 100 000 of children with the prevalence being ten-fold higher than incidence, 2. without Methotrexate treatment 4-7 years after the diagnosis of JIA-Uv cataract is revealed in 35-40% of children and in 5% – glaucoma as well, 3. even with Methotrexate in 28-40% of children the complications of JIA-Uv inevitably will be revealed with blurred vision in 10-36% of children, 4. timely diagnosis of JIA-Uv and adequate treatment reduce the risk of complications by 4% per year, 5. current medical care system reveals in one third of children already the complications of JIA-Uv. Revelation in tears of the motif mode for protein interaction network, triggering mobilization/inhibition of cells which moderate Uv would contradict the traditional point of view on existing natural anatomic and physiologic barriers, isolating the intraocular space, but however seems to be possible since JIA is a systemic disease and Uv leads to damage of the blood-retinal barriers. To reveal protein biomarkers of JIA-Uv tears of 31 children aged 2-17 years were studied: 17 – chronic JIA-Uv, 4 – JIA without Uv, 4 – idiopathic Uv, 3 – systemic vasculitis, 3 – healthy children. We used the current clinical guidelines and standards to diagnose the pathology and TMS with hierarchical clustering methodology for protein identification: nano C18 column attached to Shimadzu nano LC coupled in-line to LTQ Orbitrap XL tandem mass spectrometer, data-dependent 4-event scan method, a survey FT-MS parent scan followed by sequential data dependent FT-MS/MS scans on the three most abundant peptide ions. Proteins were identified from the mass spectra results with Proteome Discoverer 1.2 software for protein database search using the International Protein Index (IPI) and Human Protein Database. Quantification was conducted using SIEVE 2.0 after normalization to albumin keeping in mind the validity of proportional change of its concentration after stimulation of lacri-mation. Data from SIEVE were exported to IPA (Ingenuity Pathway Analysis) for filtering. The extracellular proteins selected in Ingenuity were further analyzed for disease relation and networks formation. TMS revealed more than 3000 proteins in tears and 300 of them have been considered to be the first row candidates to be biomarkers of JIA-Uv. The top two proteins, lactoferrin and lipocalin were upregulated over ten-fold in children with Uv. Pathway analysis placed these proteins into the inflammation-related IL-1 and TNF-α related networks which also included proteins involved in the development of endothelial dysfunction, inflammation and retinopathy. In addition, IL-23, which was previously linked to Uveitis, was found to be upregulated. Taken together, our proof-of-principle study presents a novel and yet untested approach for detection of early biomarkers of Uveitis and identified several candidate proteins.

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Male Gender as a Risk Factor for Complications in Uveitis Associated With Juvenile Idiopathic Arthritis

Cited by 63 publications

References 16 publications

Juvenile Idiopathic Arthritis-Associated Uveitis: Clinical Features and Complications, Risk Factors for Severe Course, and Visual Outcome

Juvenile Idiopathic Arthritis-Associated Uveitis: Clinical Features and Complications, Risk Factors for Severe Course, and Visual Outcome

Intraocular Biomarker Identification in Uveitis Associated With Juvenile Idiopathic Arthritis

Proteomic Profile of Tears for the Diagnosis of Uveitis Associated with Juvenile Idiopathic Arthritis: Setting Targets to Achieve Results

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