Potential Role of Decoy B7-H4 in the Pathogenesis of Rheumatoid Arthritis: A Mouse Model Informed by Clinical Data

AbstractThe kappa opioid receptor (KOR) and its endogenous ligands dynorphins (DYN) have been implicated in the development or symptomatology of a variety of neuropsychiatric disorders. This review covers a brief history of the development of KOR agonists and antagonists, their effects in healthy volunteers, and the potential role of DYN/KOR dysfunction in schizophrenia and major depressive disorder from a translational perspective. The potential role of DYN/KOR dysfunction in schizophrenia is based on several lines of evidence. Selective KOR agonists induce affective states in healthy volunteers with similarities to the symptoms of schizophrenia. Studies have shown increased DYN in patients with schizophrenia, although the data have been mixed. Finally, meta-analytic data have shown that opioid antagonists are associated with reductions in the symptoms of schizophrenia. The potential role of DYN/KOR dysfunction in major depressive disorder is also based on a combination of preclinical and clinical data. Selective KOR agonists have shown pro-depressive effects in human volunteers, while selective KOR antagonists have shown robust efficacy in several preclinical models of antidepressant activity. Small studies have shown that nonselective KOR antagonists may have efficacy in treatment-resistant depression. Additionally, recent clinical data have shown that the KOR may be an effective target for treating anhedonia, a finding relevant to both schizophrenia and depression. Finally, recommendations are provided for translating preclinical models for schizophrenia and major depressive disorder into the clinic.

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SAT0014 ENDOTHELIAL PROGENITOR CELLS: ROLE IN ENDOTHELIAL DAMAGE OF INTERSTITIAL LUNG DISEASE ASSOCIATED TO RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3228 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 937.1-937

Author(s):

V. Pulito-Cueto ◽

S. Remuzgo-Martínez ◽

F. Genre ◽

V. M. Mora-Cuesta ◽

D. Iturbe Fernández ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Potential Role ◽

Endothelial Damage ◽

Research Support ◽

Endothelial Progenitor

Background:Interstitial lung disease (ILD) is one of the most significant comorbidities of rheumatoid arthritis (RA), increasing the mortality in these patients [1,2]. Although the pathogenesis of ILD associated to RA (RA-ILD+) remains poorly defined [1], it is known that vascular tissue plays a crucial role in lung physiology [3]. In this context, a population of cells termed endothelial progenitor cells (EPC) are involved in vasculogenesis and endothelial tissue repair [4]. Previous reports suggest the implication of EPC in different conditions such as RA and idiopathic pulmonary fibrosis (IPF), the most common and destructive ILD [5,6]. Nevertheless, little is known about their specific role in RA-ILD+.Objectives:The purpose of this study was to shed light on the potential role of EPC in endothelial damage in RA-ILD+.Methods:Peripheral venous blood was collected from a total of 68 individuals (18 with RA-ILD+, 17 with RA-ILD-, 19 with IPF and 14 healthy controls). All subjects were recruited from the Rheumatology and Pneumology departments of Hospital Universitario Marqués de Valdecilla, Santander, Spain. Quantification of EPC was analyzed by the expression of surface antigens by flow cytometry. The combination of antibodies against the stem cell marker CD34, the immature progenitor marker CD133, the endothelial marker VEGF receptor 2 (CD309) and the common leukocyte antigen CD45 was used. EPC were considered as CD34+, CD45Low, CD309+and CD133+. All statistical analyses were performed using Prism software 5 (GraphPad).Results:EPC frequency was significantly increased in patients with RA-ILD+, RA-ILD-and IPF compared to controls (p=0.001, p=0.002, p< 0.0001, respectively). Nevertheless, patients with RA, both RA-ILD+and RA-ILD-, showed a lower frequency of EPC than those with IPF (p= 0.048, p= 0.006, respectively).Conclusion:Our results provide evidence for a potential role of EPC as a reparative compensatory mechanism related to endothelial damage in RA-ILD+, RA-ILD-and IPF patients. Interestingly, EPC frequency may help to establish a differential diagnostic between patients with IPF and those who have an underlying autoimmune disease (RA-ILD+).References:[1] J Clin Med 2019; 8: 2038;[2] Arthritis Rheumatol 2015; 67: 28-38;[3] Nat Protoc 2015; 10: 1697-1708;[4] Science 1997; 275: 964-966;[5] Rheumatology (Oxford) 2012; 51: 1775-1784;[6] Angiogenesis 2013; 16: 147-157.Acknowledgments:Personal funds, VP-C: PREVAL18/01 (IDIVAL); SR-M: RD16/0012/0009 (ISCIII-ERDF); LL-G: PI18/00042 (ISCIII-ERDF); RL-M: Miguel Servet type I CP16/00033 (ISCIII-ESF).Disclosure of Interests:Verónica Pulito-Cueto: None declared, Sara Remuzgo-Martínez: None declared, Fernanda Genre: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe Fernández: None declared, Sonia Fernández-Rozas: None declared, Leticia Lera-Gómez: None declared, Pilar Alonso Lecue: None declared, Javier Rodriguez Carrio: None declared, Belén Atienza-Mateo: None declared, Virginia Portilla: None declared, David Merino: None declared, Ricardo Blanco Grant/research support from: AbbVie, MSD, Roche, Consultant of: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Speakers bureau: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma. MSD, Alfonso Corrales Speakers bureau: Abbvie, Jose Manuel Cifrián-Martínez: None declared, Raquel López-Mejías: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD

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POTENTIAL ROLE OF REDOX SENSITIVE SERINE KINASE PATHWAYS IN THE PATHOGENESIS OF INSULIN RESISTANCE IN RHEUMATOID ARTHRITIS

International Journal of Biomedical and Advance Research ◽

10.7439/ijbar.v2i8.40 ◽

2011 ◽

Vol 2 (8) ◽

Author(s):

R. Vinayagamoorthi ◽

Zachariah Bobby ◽

A. Thiruvaimozhi

Keyword(s):

Rheumatoid Arthritis ◽

Insulin Resistance ◽

Potential Role ◽

Serine Kinase

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Potential Role of Sox9 in Patterning Tracheal Cartilage Ring Formation in an Embryonic Mouse Model

Archives of Otolaryngology - Head and Neck Surgery ◽

10.1001/archotol.130.6.732 ◽

2004 ◽

Vol 130 (6) ◽

pp. 732 ◽

Cited By ~ 21

Author(s):

Ravindhra G. Elluru ◽

Jeffrey A. Whitsett

Keyword(s):

Mouse Model ◽

Potential Role ◽

Ring Formation ◽

Embryonic Mouse ◽

Tracheal Cartilage

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Decreased MiR-128-3p alleviates the progression of rheumatoid arthritis by up-regulating the expression of TNFAIP3

Bioscience Reports ◽

10.1042/bsr20180540 ◽

2018 ◽

Vol 38 (4) ◽

Cited By ~ 11

Author(s):

Zhongbin Xia ◽

Fanru Meng ◽

Ying Liu ◽

Yuxuan Fang ◽

Xia Wu ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

Peripheral Blood ◽

Potential Role ◽

Enzyme Linked Immunosorbent Assay ◽

Normal Person ◽

Synovial Joint ◽

Peripheral Blood Mononuclear

Background: Rheumatoid arthritis (RA) is a inflammatory disease that characterized with the destruction of synovial joint, which could induce disability. Inflammatory response mediated the RA. It has been reported that MiR-128-3p is significantly increased in RA, while the potential role was still unclear. Methods: T cells in peripheral blood mononuclear cell (PBMC) were isolated from the peripheral blood from people of RA and normal person were used. Real-time PCR was performed to detect the expression of MiR-128-3p, while the protein expression of tumor necrosis factor-α-induced protein 3 (TNFAIP3) was determined using Western blot. The levels of IL-6 and IL-17 were measured using enzyme-linked immunosorbent assay (ELISA). The expression of CD69 and CD25 was detected using flow cytometry. The RA mouse model was constructed for verification of the role of MiR-128-3p. Results: The expression of MiR-128-3p was significantly increased, while TNFAIP3 was decreased, the levels of IL-6 and IL-17 were also increased in the T cells of RA patients. Down-regulated MiR-128-3p significantly suppressed the expression of p-IkBα and CD69, and CD25in T cells. MiR-128-3p targets TNFAIP3 to regulate its expression. MiR-128-3p knockdown significantly suppressed the activity of nuclear factor κB (NF-κB) and T cells by up-regulating TNFAIP3, while cells co-transfected with si-TNFAIP3 abolished the effects of MiR-128-3p knockdown. The in vivo experiments verified the potential role of MiR-128-3p on RA. Conclusion: Down-regulated MiR-128-3p significantly suppressed the inflammation response of RA through suppressing the activity of NF-κB pathway, which was mediated by TNFAIP3.

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Methylation‐dependent control of HIF‐1/VEGF axis in a mouse model of oxygen‐induced retinopathy. Potential role of the glial water channel Aquaporin‐4

Acta Ophthalmologica ◽

10.1111/aos.13972_360 ◽

2018 ◽

Vol 96 (S261) ◽

pp. 96-96

Keyword(s):

Mouse Model ◽

Potential Role ◽

Water Channel ◽

Aquaporin 4 ◽

Oxygen Induced Retinopathy

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Potential Role of Epstein-Barr Virus in Juvenile Rheumatoid Arthritis

Journal of Rheumatic Diseases ◽

10.4078/jrd.2012.19.2.65 ◽

2012 ◽

Vol 19 (2) ◽

pp. 65

Author(s):

Kyung-Sue Shin

Keyword(s):

Rheumatoid Arthritis ◽

Juvenile Rheumatoid Arthritis ◽

Epstein Barr Virus ◽

Potential Role ◽

Barr Virus ◽

Epstein Barr

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Differential diagnosis between rheumatoid arthritis and psoriatic arthritis: the value of ultrasound findings at metacarpophalangeal joints level

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.147272 ◽

2011 ◽

Vol 70 (6) ◽

pp. 1111-1114 ◽

Cited By ~ 90

Author(s):

Marwin Gutierrez ◽

Emilio Filippucci ◽

Fausto Salaffi ◽

Luca Di Geso ◽

Walter Grassi

Keyword(s):

Rheumatoid Arthritis ◽

Differential Diagnosis ◽

Psoriatic Arthritis ◽

Synovial Fluid ◽

Potential Role ◽

Power Doppler ◽

Extensor Tendon ◽

Synovial Hypertrophy ◽

Ultrasound Findings

ObjectiveTo investigate the potential of ultrasound (US) in the differential diagnosis between rheumatoid arthritis (RA) and psoriatic arthritis (PsA) at metacarpophalangeal (MCP) joints level.Methods18 RA patients and 20 PsA patients with clinical involvement of MCP joints were included. All US examinations were performed by two rheumatologists investigating: presence of joint cavity widening (JCW), synovial fluid and/or synovial hypertrophy, peritenon extensor tendon inflammation (PTI) and intra-articular or peri-tendinous power Doppler (PD) signal.ResultsA total of 83 MCP joints in 18 RA patients were assessed. In all of these the authors found different degrees of JCW. 15 of 83 (18%) MCP joints showed synovial fluid, whereas 68 of 83 (82%) MCP joints showed synovial hypertrophy. In 72 of 83 (86.7%) MCP joints intra-articular PD was detected. No PTI pattern was found in these patients.In PsA patients, a total of 82 MCP joints in 20 patients were assessed. 54 of 82 (65.8%) MCP joints showed PTI pattern (p = 0.001). In 50 of these 54 (92.5%) MCP joints extra-articular PD signal was detected (p = 0.001). 28 of 82 (34.1%) MCP joints showed different degrees of JCW. 6 of 28 (21.4%) MCP joints presented synovial fluid, whereas 22 of 28 (78.5%) MCP joints showed synovial hypertrophy. In 8 of 82 (9.7%) MCP joints the JCW and PTI patterns were found contemporaneously.ConclusionsPreliminary results demonstrate that PTI pattern is a higher characteristic of PsA, which suggests a potential role of US in the differential diagnosis between RA and PsA at MCP joints level.

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