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1.
Rogier M. Thurlings Marie Boumans Janneke Tekstra Joel A. van Roon Koen Vos Daisy Marie van Westing Lisa G. van Baarsen Carina Bos Kyriakos A. Kirou Danielle M. Gerlag Mary K. Crow Johannes W. Bijlsma Cornelis L. Verweij Paul P. Tak 《Arthritis \u0026amp; Rheumatology》2010,62(12):3607-3614
Objective
To analyze the relationship between the type I interferon (IFN) signature and clinical response to rituximab in rheumatoid arthritis (RA) patients.Methods
Twenty RA patients were treated with rituximab (cohort 1). Clinical response was defined as a decrease in the Disease Activity Score evaluated in 28 joints (DAS28) and as a response according to the European League Against Rheumatism (EULAR) criteria at week 12 and week 24. The presence of an IFN signature was analyzed in peripheral blood mononuclear cells by measuring the expression levels of 3 IFN response genes by quantitative polymerase chain reaction analysis. After comparison with the findings in healthy controls, patients were classified as having an IFN high or an IFN low signature. The data were confirmed in a second independent cohort (n = 31). Serum IFNα bioactivity was analyzed using a reporter assay.Results
In cohort 1, there was a better clinical response to rituximab in the IFN low signature group. Consistent with these findings, patients with an IFN low signature had a significantly greater reduction in the DAS28 and more often achieved a EULAR response at weeks 12 and 24 as compared with the patients with an IFN high signature in cohort 2 versus cohort 1. The pooled data showed a significantly stronger decrease in the DAS28 in IFN low signature patients at weeks 12 and 24 as compared with the IFN high signature group and a more frequent EULAR response at week 12. Accordingly, serum IFNα bioactivity at baseline was inversely associated with the clinical response, although this result did not reach statistical significance.Conclusion
The type I IFN signature negatively predicts the clinical response to rituximab treatment in patients with RA. This finding supports the notion that IFN signaling plays a role in the immunopathology of RA.2.
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Visser Tekstra Brouwer-Steenbergen Tuk Boorsma Sampat-Sardjoepersad Meijer Krediet Beelen 《Clinical and experimental immunology》1998,112(2):270-275
Recently we showed the in vivo relevance of chemokines in cases of bacterial peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. Mesothelial cells, the most numerous cells in the peritoneal cavity, are hypothesized to function as a main source of chemokine production. We investigated the time- and dose-dependent expression patterns of four chemokines by mesothelial cells at the mRNA and protein level in response to stimulation with physiological doses of proinflammatory mediators that are present at the site of bacterial inflammation. Besides the chemokines huGRO-α (attractant for neutrophils), MCP-1 and RANTES (monocyte attractants), the expression and production of IP-10 was analysed. Mesothelial cells were cultured and stimulated with either IL-1β, tumour necrosis factor-alpha (TNF-α) or IFN-γ or combinations of these. The time- and dose-dependent mRNA expression of the chemokines was determined by Northern blot analysis and the protein production by ELISA. It was concluded that mesothelial cells could indeed be triggered by the mentioned stimuli to induce mRNA and protein production (huGRO-α and IP-10) or to augment constitutive protein production (MCP-1). However, RANTES mRNA and protein production could only be induced in some cases and only in small amounts. The chemokine response of mesothelial cells was regulated differentially, depending on the stimulus and the chemokine measured. In distinct cases, combination of the stimuli led to synergy in mRNA expression and protein production. The presented in vitro data support our hypothesis that mesothelial cells in vivo are the main source of relevant chemokines in response to proinflammatory mediators, suggesting an important role for mesothelial cells in host defence. 相似文献
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G. Wheater V. E. Hogan Y. K. O. Teng J. Tekstra F. P. Lafeber T. W. J. Huizinga J. W. J. Bijlsma R. M. Francis S. P. Tuck H. K. Datta J. M. van Laar 《Osteoporosis international》2011,22(12):3067-3072
Summary
The role of B cells in inflammatory bone formation and resorption is controversial. We investigated this in patients with rheumatoid arthritis (RA) treated with rituximab, a B-cell depleting antibody. We found a significant suppression in bone turnover, possibly a direct effect or as a consequence of a reduction in inflammation and disease activity.Introduction
RA is the most prevalent inflammatory joint disease, in which B cells play an important role. However, the role of B cells in bone turnover is controversial and RA subjects treated with rituximab, a B-cell depleting monoclonal antibody, provide an ideal model for determining the role of B cells in inflammatory bone resorption.Methods
Serum from 46 RA patients, collected pre- and post-rituximab therapy, was analysed for biomarkers of bone turnover (procollagen type I amino-terminal propeptide [P1NP], osteocalcin, ??-isomerised carboxy-terminal telopeptide of type 1 collagen [??CTX] and osteoprotegerin [OPG]).Results
A significant decrease in bone resorption was observed 6?months after rituximab (median change ??CTX ?50?ng/L, 95%CI ?136, ?8 p?<?0.001, this equates to ?37%; 95%CI ?6, ?49), mirrored by a reduction in disease activity. Similarly, there was a significant increase in P1NP, a marker of bone formation (median change P1NP 5.0???g/L, 95%CI ?1.0, 11.2, p?=?0.02; 13%; 95%CI ?3, 39), but no significant change in osteocalcin or OPG levels. The percentage change from baseline of ??CTX in a subgroup of patients (not on prednisolone or bisphosphonate) was significantly correlated with the percentage reduction in DAS28 score (r s?=?0.570, p?=?0.014).Conclusions
In conclusion, we have found that B-cell depletion increases bone formation and decreases bone resorption in RA patients; this may be a direct effect on osteoblasts and osteoclasts, respectively, and be at least partially explained by the decreased inflammation and disease activity. 相似文献6.
Systemic Lupus Erythematosus (SLE), because of its complex and multisystemic presentation, lacks a reliable and sensitive gold standard for measuring disease activity. In addition, there is no standardized method for defining response to therapy. Several disease activity indices have been developed over the years, each with their own positive and negative aspects. Growing insight in the pathogenesis of inflammatory diseases like SLE leads to the introduction of specific targeted biologic therapies. To investigate the efficacy of these new biologic agents, disease activity must be monitored regularly by a reliable and validated instrument. Recent studies on new biologics for treatment of SLE use a new composite measurement for disease activity and response in SLE. This new disease activity assessment, called SLE Responder Index (SRI), comprises criteria from three different internationally validated indices, SELENA-SLE Disease Activity Index (SELENA-SLEDAI), Physician Global Assessment (PGA) and the British Isles Lupus Assessment Group (BILAG) 2004. This review gives an overview of current available disease activity indices in relation to the newly developed composite SRI. 相似文献
7.
Anne‐Mieke J. W. Haasnoot Naïlah F. M. Sint Jago Janneke Tekstra Joke H. de Boer 《Arthritis care & research》2017,69(12):1895-1902
Objective
To establish the impact of uveitis on the quality of life (QoL) in adult patients with juvenile idiopathic arthritis (JIA ).Methods
Adult patients with a history of JIA , both with (n = 31) or without (n = 51) chronic anterior uveitis, were included. Their scores on 3 validated QoL questionnaires (National Eye Institute Visual Functioning Questionnaire [NEI VFQ ‐25], Medical Outcomes Study 36‐Item Short Form health survey [SF ‐36], and EuroQol 5‐domain questionnaire [EQ ‐5D]) were analyzed to find factors that could influence QoL.Results
The median overall composite score (OCS ) of the NEI VFQ ‐25 was significantly worse in the uveitis group compared to the non‐uveitis group (respectively, 83.4 [range 15.2–94.7] and 94.9 [range 46.3–100]; P < 0.001). Nearly all subscale scores were lower in patients with uveitis than in patients without uveitis (P < 0.001 for all). After adjusting for duration of arthritis, JIA subtype, arthritis onset before or after 1990, and the use of systemic immunomodulatory medication, the QoL was still worse in patients with uveitis (NEI VFQ ‐25 OCS regression coefficient = ?11.7; P = 0.002). No significant differences were found between the groups for the SF ‐36 and the EQ ‐5D. In the total JIA group, the use of systemic medication appeared to negatively influence some general QoL scores.Conclusion
Having a history of uveitis has a substantial negative effect on the vision‐related QoL in JIA in adulthood, despite good visual acuity. General QoL scores did not differ between uveitis and non‐uveitis patients, but the use of systemic immunomodulatory treatment, independent of uveitis, did negatively influence general QoL scores in adult JIA patients.8.
J Tekstra H Beekhuizen J S Van De Gevel I J Van Benten C W Tuk R H Beelen 《Clinical and experimental immunology》1999,117(3):489-495
Bacterial infection coincides with migration of leucocytes from the circulation into the bacterium-infected tissue. Recently, we have shown that endothelial cells, upon binding and ingestion of Staphylococcus aureus, exhibit proinflammatory properties including procoagulant activity and increased intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression on the cell surface, resulting in hyperadhesiveness, mainly for monocytes. The enhanced extravasation of monocytes to bacterium-infected sites is facilitated by the local production of chemotactic factors. From another study we concluded that the locally produced chemokine MCP-1 is important in the recruitment of monocytes to the peritoneal cavity in a model of bacterial peritonitis. In the present study we investigated whether cultured human endothelial cells after infection with bacteria produce and release MCP-1, which in turn stimulates monocyte chemotaxis. We observed that endothelial cells released significant amounts of MCP-1 within 48 h after ingestion of S. aureus. This was dependent on the number and the virulence of the bacteria used to infect the endothelial cells. The kinetics as well as the amount of MCP-1 released by S. aureus-infected endothelial cells differed markedly from that released by endothelial cells upon stimulation with IL-1beta. Supernatant from S. aureus-infected or IL-1beta-stimulated cells promoted monocyte chemotaxis which was almost entirely abrogated in the presence of neutralizing anti-MCP-1 antibody, indicating that most of the chemotactic activity was due to the release of MCP-1 into the supernatant. Our findings support the notion that endothelial cells can actively initiate and sustain an inflammatory response after an encounter with pathogenic microorganisms, without the intervention of macrophage-derived proinflammatory cytokines. 相似文献
9.
Marjan Ghiti Moghadam Harald E. Vonkeman Peter M. ten Klooster Janneke Tekstra Dirkjan van Schaardenburg Mirian Starmans‐Kool Elisabeth Brouwer Reinhard Bos Willem F. Lems Edgar M. Colin Cornelia F. Allaart Inger L. Meek Robert Landew Hein J. Bernelot Moens Piet L. C. M. van Riel Mart A. F. J. van de Laar Tim L. Jansen 《Arthritis \u0026amp; Rheumatology》2016,68(8):1810-1817
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