S100 Proteins, Cytokines, and Chemokines as Tear Biomarkers in Children with Juvenile Idiopathic Arthritis-associated Uveitis

Angeles‐Han, Sheila T.; Utz, Virginia Miraldi; Thornton, Sherry; Schulert, Grant S.; Rodriguez-Smith, Jackeline; Kauffman, Adam; Sproles, Alyssa; Mwase, Najima; Hennard, Theresa; Grom, Alexei A.; Altaye, Mekibib; Holland, Gary N.

doi:10.1080/09273948.2020.1758731

Cited by 15 publications

(12 citation statements)

References 14 publications

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“…IFN-g was significantly elevated in the serum of active patients, suggesting the imbalance of the Th1/Th2 immune response (39,40). Previews studies have revealed that mechanisms of AU are closely related to enhanced activity of the IL-23/IL-17 pathway (41). Likewise, previous studies concerning noninfectious uveitis have found that various proinflammatory cytokines such as IL-1, IL-2, IL-6, IL-15, IFN-g, TNF-a, IL-17, IL-23, IL-8, MCP-1, MIP-1b, IL-10, TGIF-b were elevated in serum, aqueous humor or vitreous (42).…”

Section: Discussionmentioning

confidence: 99%

Study of the shared gene signatures of polyarticular juvenile idiopathic arthritis and autoimmune uveitis

Zheng

Wang

2023

Front. Immunol.

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ObjectiveTo explore the shared gene signatures and potential molecular mechanisms of polyarticular juvenile idiopathic arthritis (pJIA) and autoimmune uveitis (AU).MethodThe microarray data of pJIA and AU from the Gene Expression Omnibus (GEO) database were downloaded and analyzed. The GEO2R tool was used to identify the shared differentially expressed genes (DEGs) and genes of extracellular proteins were identified among them. Then, weighted gene co-expression network analysis (WGCNA) was used to identify the shared immune-related genes (IRGs) related to pJIA and AU. Moreover, the shared transcription factors (TFs) and microRNAs (miRNAs) in pJIA and AU were acquired by comparing data from HumanTFDB, hTFtarget, GTRD, HMDD, and miRTarBase. Finally, Metascape and g: Profiler were used to carry out function enrichment analyses of previously identified gene sets.ResultsWe found 40 up-regulated and 15 down-regulated shared DEGs via GEO2R. Then 24 shared IRGs in positivity-related modules, and 18 shared IRGs in negatively-related modules were found after WGCNA. After that, 3 shared TFs (ARID1A, SMARCC2, SON) were screened. And the constructed TFs-shared DEGs network indicates a central role of ARID1A. Furthermore, hsa-miR-146 was found important in both diseases. The gene sets enrichment analyses suggested up-regulated shared DEGs, TFs targeted shared DEGs, and IRGs positivity-correlated with both diseases mainly enriched in neutrophil degranulation process, IL-4, IL-13, and cytokine signaling pathways. The IRGs negatively correlated with pJIA and AU mainly influence functions of the natural killer cell, cytotoxicity, and glomerular mesangial cell proliferation. The down-regulated shared DEGs and TFs targeted shared DEGs did not show particular functional enrichment.ConclusionOur study fully demonstrated the flexibility and complexity of the immune system disorders involved in pJIA and AU. Neutrophil degranulation may be considered the shared pathogenic mechanism, and the roles of ARID1A and MiR-146a are worthy of further in-depth study. Other than that, the importance of periodic inspection of kidney function is also noteworthy.

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Section: Discussionmentioning

confidence: 99%

Study of the shared gene signatures of polyarticular juvenile idiopathic arthritis and autoimmune uveitis

Zheng

Wang

2023

Front. Immunol.

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“…In the presence of IL8, neutrophils show a flattened and elongated morphology, which is characteristic for the migration process [ 35 ]. Increased levels of IL8 have been described in blood and vitreous of uveitis patients with Behçet’s disease [ 36 , 37 ] and IL8 was significantly increased in tears of children with Juvenile Idiopathic Arthritis-associated Uveitis during an episode of active uveitis, but not in quiescent stage [ 38 ]. Moreover, IL8 and the upregulation of its receptors have been linked to disease severity in several rodent models for different types of uveitides [ 39 , 40 , 41 ] and the IL8 homologue in mice, CXCL1, has been suggested to take part in neutrophil infiltration in RBP-3 induced experimental autoimmune uveitis (EAU) [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

Pre-Activated Granulocytes from an Autoimmune Uveitis Model Show Divergent Pathway Activation Profiles upon IL8 Stimulation In Vitro

Hoffmann¹,

Hauck

Deeg³

et al. 2022

IJMS

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In the pathophysiology of autoimmune-mediated uveitis, granulocytes have emerged as possible disease mediators and were shown to be pre-activated in equine recurrent uveitis (ERU), a spontaneous disease model. We therefore used granulocytes from ERU horses to identify early molecular mechanisms involved in this dysregulated innate immune response. Primary granulocytes from healthy and ERU horses were stimulated with IL8, and cellular response was analyzed with differential proteomics, which revealed significant differences in protein abundance of 170 proteins in ERU. Subsequent ingenuity pathway analysis identified three activated canonical pathways “PKA signaling”, “PTEN signaling” and “leukocyte extravasation”. Clustered to the leukocyte extravasation pathway, we found the membrane-type GPI-anchored protease MMP25, which was increased in IL8 stimulated ERU granulocytes. These findings point to MMP25 as a possible regulator of granulocyte extravasation in uveitis and a role of this molecule in the impaired integrity of the blood-retina-barrier. In conclusion, our analyses show a clearly divergent reaction profile of pre-activated granulocytes upon IL8 stimulation and provide basic information for further in-depth studies on early granulocyte activation in non-infectious ocular diseases. This may be of interest for the development of new approaches in uveitis diagnostics and therapy. Raw data are available via ProteomeXchange with identifier PXD013648.

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“…Of note, unveiling new non-invasive biomarkers could be a field of particular interest in patients affected by juvenile idiopathic arthritis (JIA) with eye manifestations, as it commonly manifests as chronic anterior uveitis, which is often clinically silent and can lead to serious visual impairment [ 50 ]. Angeles-Han et al [ 51 ] showed a different proteomic tear profile between patients with JIA-associated uveitis and healthy patients, S100, IL-8 and soluble intracellular adhesion molecule (sICAM1), a potential biomarker for disease activity. Moreover, it has been shown that the proteomic profile between patients with JIA-associated uveitis and idiopathic uveitis could also be different [ 22 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

Tear and Plasma Levels of Cytokines in Patients with Uveitis: Search for Active Disease Biomarkers

García-Onrubia

Olivares

Garcı́a-Vázquez

et al. 2022

JCM

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Uveitis accounts for up to 20% of blindness in Europe, making the development of new non-invasive biomarkers which could help in its management a field of interest. It has been hypothesised that tear levels of cytokines and chemokines could be used as a potential biomarker in patients with anterior uveitis, and this could be correlated with their concentration in plasma. Therefore, we measured twelve cytokines/chemokines in tear and plasma samples of 22 patients diagnosed with active anterior uveitis. Levels of these molecules in tears and plasma were compared and associated with the degree of activity of the uveitis. It is notable that the percentage of tear interleukin (IL)-6 detection was significantly reduced in the inactive phase (p < 0.05). However, the tear concentration in epidermal growth factor (EGF), fractalkine, IL-8, IL-1RA, interferon-inducible protein (IP)-10/CXCL10, vascular endothelial growth factor (VEGF) and IL-6, comparing the active and inactive period, was not statistically different. Apart from the tear VEGF levels, the cytokine/chemokine concentration in tears in the active/inactive phase was statistically different (p < 0.05) from the counterpart levels in plasma. In conclusion, no isolated cytokine/chemokine in the tears has been found in a concentration which could be used as a potential biomarker of disease activity and treatment response.

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S100 Proteins, Cytokines, and Chemokines as Tear Biomarkers in Children with Juvenile Idiopathic Arthritis-associated Uveitis

Cited by 15 publications

References 14 publications

Study of the shared gene signatures of polyarticular juvenile idiopathic arthritis and autoimmune uveitis

Study of the shared gene signatures of polyarticular juvenile idiopathic arthritis and autoimmune uveitis

Pre-Activated Granulocytes from an Autoimmune Uveitis Model Show Divergent Pathway Activation Profiles upon IL8 Stimulation In Vitro

Tear and Plasma Levels of Cytokines in Patients with Uveitis: Search for Active Disease Biomarkers

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