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  • BMJ  (12)
  • Wang, J.  (12)
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  • BMJ  (12)
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  • 1
    Online Resource
    Online Resource
    BMJ ; 2020
    In:  Annals of the Rheumatic Diseases Vol. 79, No. Suppl 1 ( 2020-06), p. 1329.1-1329
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 1329.1-1329
    Abstract: CD163, a hemoglobin scavenger receptor, has been identified as a marker of M2 macrophages, it can promote the release of IL-10 and carbon oxide. Researches on inflammatory diseases and tumors have suggested that CD163 plays anti-inflammatory effect and promotes tumor growth and metastasis. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by chronic synovitis with inflammatory cells infiltration including considerable macrophages. However, little is known about the role of CD163+ macrophages in RA synovium. Objectives: To investigate the expression and clinical significance of synovial CD163+ macrophages in RA. Methods: Seventy-five RA patients were recruited and clinical data including disease activity, HAQ and Sharp/van der Heijde-modified Sharp score of bilateral hands and wrists were collected. Synovial tissues were obtained by needle biopsies or arthroscopy of knee joints. Eighteen osteoarthritis (OA) and seventeen orthopedic arthropathies (orth.A) patients were included as controls. All synovium were stained with H & E and immunohistochemically for CD163, CD3, CD20, CD38, CD68, and CD15. Histologic changes of synovitis in H & E stained sections were graded with Krenn’s synovitis score. Results: Positive CD163 expression were found in both lining synoviocytes and sublining inflammatory cells. Both densities of lining and sublining CD163+ macrophages in RA synovium were significantly higher than that in OA or Orth.A synovium (140.47±66.93 vs. 17.85±7.70 vs. 19.76±5.26 and 417.92±249.62 vs. 27.58±14.19 vs. 29.87±9.33, all P 〈 0.001, Figure 1). According to Krenn’s synovitis score, there were 68% RA patients showing high synovitis (score 〉 4). Both lining and sublining synovial CD163+ macrophages were significantly higher than those showing low synovitis (lining: 158.40±62.91 vs. 122.06±66.74, sublining: 462.96±62.91 vs. 371.65±271.54, both P 〈 0.05). Meanwhile, the densities of lining and sublining CD163+ macrophages were both positively correlated with Krenn’s synovitis score ( r =0.238 and 0.343, both P 〈 0.05). For clinical relationship in RA, the density of sublining CD163+ macrophages was positively correlated with total Sharp score (mTSS) ( r =0.399, P 〈 0.001), joint space narrowing subscore ( r =0.248, P =0.032) and joint erosion subscore ( r =0.457, P 〈 0.001). While the density of lining CD163+ macrophages was positively correlated with mTSS ( r =0.319, P =0.005) and joint erosion subscore ( r= 0.358, P =0.002). Meanwhile, the densities of sublining and lining CD68+ macrophages were also positively correlated with mTSS ( r =0.253 and 0.242, both P 〈 0.05), of which the correlation was weaker than that of CD163+ macrophages (Figure 2). There were no significant correlation between the density of CD163+ macrophages and disease activity or HAQ (all P 〉 0.05). Conclusion: Synovial CD163+ macrophages are associated with radiographic joint destruction, which imply that CD163+ macrophages may play role in the pathogenisis of joint destruction in RA. Figure 1. Representative immunohistochemical findings of synovial CD163 expression. (A) Synovial CD163 expression in an Orth.A patient, an OA patient and a RA patient. (B) Densities of lining and sublining CD163+ macrophages in Orth.A, OA and RA patients. Figure 2. Spearman’s rank correlation analysis for synovial macrophages and mTSS in RA. (A) Correlation between sublining CD163+ macrophages and mTSS, joint space narrowing subscore, joint erosion subscore. (B) Correlation between lining CD163+ macrophages and mTSS, joint space narrowing subscore, joint erosion subscore. Funding: : This work was supported by National Natural Science Foundation of China (no. 81801606 and 81971527), Guangdong Natural Science Foundation (no. 2017A030313576, 2018A030313541 and 2019A1515011928). Figures: Disclosure of Interests: None declared
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1481557-6
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  • 2
    In: BMJ Open, BMJ, Vol. 5, No. 5 ( 2015-05-15), p. e006886-e006886
    Type of Medium: Online Resource
    ISSN: 2044-6055
    Language: English
    Publisher: BMJ
    Publication Date: 2015
    detail.hit.zdb_id: 2599832-8
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  • 3
    Online Resource
    Online Resource
    BMJ ; 2010
    In:  Injury Prevention Vol. 16, No. Supplement 1 ( 2010-09-01), p. A134-A134
    In: Injury Prevention, BMJ, Vol. 16, No. Supplement 1 ( 2010-09-01), p. A134-A134
    Type of Medium: Online Resource
    ISSN: 1353-8047
    Language: English
    Publisher: BMJ
    Publication Date: 2010
    detail.hit.zdb_id: 2077803-X
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  • 4
    Online Resource
    Online Resource
    BMJ ; 2011
    In:  British Journal of Ophthalmology Vol. 95, No. 4 ( 2011-04-01), p. 509-513
    In: British Journal of Ophthalmology, BMJ, Vol. 95, No. 4 ( 2011-04-01), p. 509-513
    Type of Medium: Online Resource
    ISSN: 0007-1161
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2011
    detail.hit.zdb_id: 1482974-5
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  • 5
    Online Resource
    Online Resource
    BMJ ; 2022
    In:  Annals of the Rheumatic Diseases Vol. 81, No. Suppl 1 ( 2022-06), p. 500.1-500
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 81, No. Suppl 1 ( 2022-06), p. 500.1-500
    Abstract: Takayasu arteritis (TAK) is a chronic granulomatous large vessel vasculitis with multiple immune cells involved [1]. In TAK, vascular lesions originate from the vascular adventitia. The vascular adventitia is rich in vasa vasorum, which can transport peripheral immune cells to active vascular lesions in the early stage of lesion development [2] . Thus, chemokines played critical roles in the pathogenesis of TAK. It has been reported that the levels of RANTES, CCL2, CCL20, CXCL8, and CXCL10 were elevated in TAK, and their levels were correlated with disease activity [3, 4]. However, the profile of chemokines in TAK has not been clearly elucidated. Objectives This study aimed to investigate chemokine profile in peripheral blood and vascular tissue of patients with TAK. Methods A total of 58 patients with TAK and 53 healthy controls were enrolled. Chemokine array assay was performed in five patients with TAK and three controls. Chemokines with higher levels were preliminarily validated in 20 patients and controls. The validated chemokines were further confirmed in another group of samples with 25 patients and 25 controls. Their expression and distribution were also examined in vascular tissue from 8 patients and 5 controls. Correlations between these chemokines and peripheral immune cells, cytokines, disease activity parameters were analyzed. Their serum changes were also investigated in these 45 patients after glucocorticoids and immunosuppressive treatment. Results Patients and controls were age and sex-matched. Twelve higher chemokines and 4 lower chemokines were found based on the chemokine array. After validation, increase of 5 chemokines were confirmed in patients with TAK, including CCL22, RANTES, CXCL16, CXCL11, and IL-16. Their expressions were also increased in vascular tissue of patients with TAK. In addition, levels of RANTES and IL-16 were positively correlated with peripheral CD3+CD4+ T cell numbers. Close localization of CCL22, CXCL11 or IL-16 with inflammatory cells were also observed in TAK vascular tissue. No correlations were found between these chemokines and cytokines (IL-6, IL-17, IFN-γ) or inflammatory parameters (ESR, CRP). No differences were observed regarding with these chemokines between active and inactive patients. After treatment, increase of CCL22 and decrease of RANTES, CXCL16 were found, while no changes were showed in levels of CXCL11 and IL-16. Conclusion CCL22, RANTES, CXCL16, CXCL11, and IL-16 were identified as the major chemokines involved in the recruitment of immune cells in the vascular tissue of patients with TAK. Additionally, the persistently high levels of CCL22, CXCL11, and IL-16 observed after treatment indicate their role in vascular chronic inflammation or fibrosis and demonstrate the need for developing more efficacious treatment options. References [1]Seyahi E. Takayasu arteritis: an update. Curr Opin Rheumatol. 2017 Jan;29(1):51-56. [2]Corbera-Bellalta M, Planas-Rigol E, Lozano E, Terrades-García N, Alba MA, Prieto-González S, García-Martínez A, Albero R, Enjuanes A, Espígol-Frigolé G, Hernández-Rodríguez J, Roux-Lombard P, Ferlin WG, Dayer JM, Kosco-Vilbois MH, Cid MC. Blocking interferon γ reduces expression of chemokines CXCL9, CXCL10 and CXCL11 and decreases macrophage infiltration in ex vivo cultured arteries from patients with giant cell arteritis. Ann Rheum Dis. 2016 Jun;75(6):1177-86. [3]Noris M, Daina E, Gamba S, Bonazzola S, Remuzzi G. Interleukin-6 and RANTES in Takayasu arteritis: a guide for therapeutic decisions? Circulation. 1999 Jul 6;100(1):55-60. [4]Dong H, Zhang Y, Zou Y, Chen Y, Yue J, Liu H, Jiang X. Elevated chemokines concentration is associated with disease activity in Takayasu arteritis. Cytokine. 2021 Jul;143:155515. Disclosure of Interests None declared.
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 1481557-6
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  • 6
    Online Resource
    Online Resource
    BMJ ; 2010
    In:  Heart Vol. 96, No. Suppl 3 ( 2010-10-01), p. A145-A145
    In: Heart, BMJ, Vol. 96, No. Suppl 3 ( 2010-10-01), p. A145-A145
    Type of Medium: Online Resource
    ISSN: 1355-6037
    Language: English
    Publisher: BMJ
    Publication Date: 2010
    detail.hit.zdb_id: 1475501-4
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  • 7
    In: Heart, BMJ, Vol. 96, No. Suppl 3 ( 2010-10-01), p. A145-A146
    Type of Medium: Online Resource
    ISSN: 1355-6037
    Language: English
    Publisher: BMJ
    Publication Date: 2010
    detail.hit.zdb_id: 1475501-4
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  • 8
    Online Resource
    Online Resource
    BMJ ; 2011
    In:  Heart Vol. 97, No. Suppl 3 ( 2011-10-01), p. A39-A40
    In: Heart, BMJ, Vol. 97, No. Suppl 3 ( 2011-10-01), p. A39-A40
    Type of Medium: Online Resource
    ISSN: 1355-6037
    Language: English
    Publisher: BMJ
    Publication Date: 2011
    detail.hit.zdb_id: 1475501-4
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  • 9
    In: BMJ Open, BMJ, Vol. 5, No. 11 ( 2015-11-11), p. e009305-e009305
    Type of Medium: Online Resource
    ISSN: 2044-6055
    Language: English
    Publisher: BMJ
    Publication Date: 2015
    detail.hit.zdb_id: 2599832-8
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  • 10
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 81, No. Suppl 1 ( 2022-06), p. 687.2-688
    Abstract: Takayasu’s arteritis (TAK) is a chronic, non-specific, granulomatous macrovasculitis and its pathogenesis is still unclear. The increasing evidence indicated that multiple pathological process involved in the development of TAK. According to previous reports, multiple biomarkers representative different pathological process (1-3), However, which biomarker can closely reflect disease activity or vascular changes and whether these abnormal processes can be prevented by current therapies remained unknown. Objectives To analyze changes of serum cytokine, chemokine, and growth factor profiles in patients with Takayasu arteritis (TAK) after tofacitinib treatment and explore potential molecular signatures related with various disease characteristics Methods Seventeen patients from a TAK cohort treated with tofacitinib and 12 healthy controls were recruited in this study. Potential biomarkers with TAK including cytokines, MMPs, chemokines and growth factors were detected in these patients (0, 6, 12 months) and healthy controls. Molecular changes, disease activity, disease remission, and vascular imaging changes were analyzed in these patients after treatment. Furthermore, molecule signatures associated with these clinical features/outcomes were explored via radar plot and correlation analysis. Results At baseline, all the patients were in active status. Meanwhile, patients’ cytokines (PTX3, IL-6, IFN-γ), chemokines (IL-16, CCL22, CCL2), growth factor (VEGF) and MMP9 were significantly higher than those of healthy controls (all p 〈 0.05), while FGF-2 was significantly lower in patients with TAK (p=0.02). After treatment, 94.12% of patients achieved complete remission at 6 and 12 months; patients’ ESR and CRP levels were significantly reduced at 6 months (p=0.02, p=0.046 respectively); vascular improvement were observed in 6 (35.29%) patients at 12 months. With regards to these molecules, IL-10 was increased at 6 months compared with its baseline level (p=0.007). No changes were observed in other cytokines, chemokines, or growth factors. Besides, the radar plot demonstrated that PTX3 was closely correlated with disease activity. In addition, patients with vascular imaging improvement had relatively higher baseline levels of TNFα, ESR, and CRP (p=0.04, p=0.056, p=0.07, respectively), lower CCL22, FGF, and PDGF-AB levels (p=0.056, p=0.06 and p=0.08 respectively) compared with patients without it. Conclusion Multiple molecules representative different pathological mechanism participated in the pathogenesis of TAK. PTX3 was a prominent marker for disease activity, and CCL22 may have a predictive value for vascular imaging changes. References [1]Dagna L, Salvo F, Tiraboschi M, et al. Pentraxin-3 as a marker of disease activity in Takayasu arteritis. Ann Intern Med . 2011;155(7):425-433. doi:10.7326/0003-4819-155-7-201110040-00005 [2]Sun Y, Kong X, Wu S, et al. YKL-40 as a new b iomarker of disease activity in Takayasu arteritis. Int J Cardiol . 2019; 293: 231-237 [3]Dong H, Zhang Y, Zou Y, et al. Elevated chemokines concentration is associated with disease activity in Takayasu arteritis. Cytokine . 2021; 143: 155515 Disclosure of Interests None declared
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 1481557-6
    Location Call Number Limitation Availability
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