Immunopathophysiology and clinical impact of uveitis in inflammatory rheumatic diseases: An update

Hysa, Elvis; Cutolo, Carlo Alberto; Gotelli, Emanuele; Pacini, G.; Schenone, C.; Kreps, Elke O.; Smith, Vanessa; Cutolo, Maurizio

doi:10.1111/eci.13572

Cited by 24 publications

(20 citation statements)

References 98 publications

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“…MAdCAM-1 is induced by TNF-α in diverse endothelial cells and recruits T-cells to inflamed tissues 83 – 85 and, therefore, has recently been identified as an interesting target to treat inflammatory bowel diseases 86 . In addition to Madcam1 upregulation, we observed T-cell infiltration in our AAV-TNF-α driven uveitis-like model, in line with well-described role for T-cells in uveitis patients and uveitis rodent models 87 , 88 . Although there is general interest in the role of TNF-α and CAMs in the context of retinopathies, to our knowledge there exists only one recent study by Peng et al .…”

Section: Discussionsupporting

confidence: 88%

Transcriptome analysis of AAV-induced retinopathy models expressing human VEGF, TNF-α, and IL-6 in murine eyes

Becker

Weigelt²,

Fuchs³

et al. 2022

Sci Rep

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Retinopathies are multifactorial diseases with complex pathologies that eventually lead to vision loss. Animal models facilitate the understanding of the pathophysiology and identification of novel treatment options. However, each animal model reflects only specific disease aspects and understanding of the specific molecular changes in most disease models is limited. Here, we conducted transcriptome analysis of murine ocular tissue transduced with recombinant Adeno-associated viruses (AAVs) expressing either human VEGF-A, TNF-α, or IL-6. VEGF expression led to a distinct regulation of extracellular matrix (ECM)-associated genes. In contrast, both TNF-α and IL-6 led to more comparable gene expression changes in interleukin signaling, and the complement cascade, with TNF-α-induced changes being more pronounced. Furthermore, integration of single cell RNA-Sequencing data suggested an increase of endothelial cell-specific marker genes by VEGF, while TNF-α expression increased the expression T-cell markers. Both TNF-α and IL-6 expression led to an increase in macrophage markers. Finally, transcriptomic changes in AAV-VEGF treated mice largely overlapped with gene expression changes observed in the oxygen-induced retinopathy model, especially regarding ECM components and endothelial cell-specific gene expression. Altogether, our study represents a valuable investigation of gene expression changes induced by VEGF, TNF-α, and IL-6 and will aid researchers in selecting appropriate animal models for retinopathies based on their agreement with the human pathophysiology.

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Section: Discussionsupporting

confidence: 88%

Transcriptome analysis of AAV-induced retinopathy models expressing human VEGF, TNF-α, and IL-6 in murine eyes

Becker

Weigelt²,

Fuchs³

et al. 2022

Sci Rep

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“…Compared to healthy individuals, the number of Th17 cells is increased in the peripheral blood of BD patients, while the number of Treg cells decreases. Additionally, in vitro normal CD4+ T cells stimulated with serum from patients with active BD showed increased Th17 cell differentiation and decreased Treg cell differentiation compared to CD4+ T cells stimulated with serum from BD patients in remission (24,25).…”

Section: Discussionmentioning

confidence: 97%

Case report and analysis: Behçet’s disease with lower extremity vein thrombosis and pseudoaneurysm

Wang

Zhang

et al. 2022

Front. Immunol.

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BackgroundBehçet’s disease (BD) is a unique autoimmune chronic systemic vasculitis that affects veins and arteries of all sizes. BD can lead to recurrent vascular events, especially venous thrombosis, with an incidence rate of 40%, or pseudoaneurysms formed under long-term inflammatory reaction or iatrogenic stimulation. BD-related risk factors promote endothelial dysfunction, platelet activation and overactivation of tissue factors leading to mural inflammatory thrombi. Thrombosis may be the first clinical manifestation of BD.Case presentationA 32-year-old man complaining of progressive swelling and pain in the right lower extremity for 30 days was initially diagnosed with “venous thrombosis of the right lower extremity,” using color Doppler ultrasonography. Patient underwent inferior vena cava filter placement combined with deep vein angioplasty of the right lower extremity and catheter-directed urokinase thrombolysis. Postoperative oral anticoagulant therapy was administered. However, the patient was readmitted 20 days later for pulsatile pain in the right groin. Prior medical history included 4 years of repeated oral and perineal ulcers, and 2 months of blurred vision. Abdominal computed tomography angiography (CTA) revealed rupture of the right common iliac artery (CIA) and left internal iliac artery (IIA), complicated by a pseudoaneurysm. Based on the clinical manifestations and other auxiliary examination results, the patient was re-diagnosed with “BD combined with deep venous thrombosis of the right lower extremity and an iliac artery pseudoaneurysm.” Stent implantation was performed for iliac artery pseudoaneurysm after symptoms were controlled with timely immunosuppressive therapy. After endovascular treatment, the patient underwent continued immunosuppressive therapy and dynamic reexaminations of abdominal CTA, which revealed that a small amount of contrast agent at the stent in the right CIA continued to flow into the cavity of the pseudoaneurysm; in addition, the size of the pseudoaneurysm was gradually increasing. Therefore, the patient underwent a second stent implantation for iliac artery pseudoaneurysm, and the condition improved further.ConclusionThe importance of early diagnosis of BD should be recognized, and the choice of interventional and surgical procedures should be carefully evaluated, as this may trigger further damage to vascular access in BD patients with aneurysm.

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“…The key players of ocular BS seem to be highly polarised Th1 and Th17 lymphocytes, natural killer T cells and γδ T cells, since they contribute to a highly destructive inflammatory environment (15). Another group studied the metabolite composition of sweat in BS ( 16) by metabolomics analysis and liquid chromatography tandem mass spectrometry and showed significant differences between BS and HCs in l-citrulline, l-pyroglutamic acid, uro-canic acid, 2-oxoadipic acid, cholesterol 3-sulfate, and pentadecanoic acid levels.…”

Section: Immunopathogenesismentioning

confidence: 99%

Behçet's syndrome: one year in review 2022

Hatemi

Seyahi

Fresko

et al. 2022

Clinical and Experimental Rheumatology

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This review highlights publications on different aspects of Behçet's syndrome (BS) that appeared in 2021 and provides a critical view. These publications include works on the epidemiology of BS across different continents, newly developed instruments to assess damage in BS, studies highlighting the immunopathogenesis, genetics and epigenetic factors, histopathology of the pathergy lesion, clinical and imaging aspects of vascular involvement, and safety and efficacy of therapeutic agents including tocilizumab, apremilast and direct oral anticoagulants.

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Immunopathophysiology and clinical impact of uveitis in inflammatory rheumatic diseases: An update

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 24 publications

References 98 publications

Transcriptome analysis of AAV-induced retinopathy models expressing human VEGF, TNF-α, and IL-6 in murine eyes

Transcriptome analysis of AAV-induced retinopathy models expressing human VEGF, TNF-α, and IL-6 in murine eyes

Case report and analysis: Behçet’s disease with lower extremity vein thrombosis and pseudoaneurysm

Behçet's syndrome: one year in review 2022

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