Treatment-induced remission in rheumatoid arthritis patients is characterized by a reduction in macrophage content of synovial biopsies

Smith, Malcolm D.; Kraan, Maarten C.; Slavotinek, John; Au, Virginia; Weedon, Helen; Parker, Angela; Coleman, Mark; Roberts‐Thomson, Peter; Ahern, Michael

doi:10.1093/rheumatology/40.4.367

Cited by 52 publications

(45 citation statements)

References 8 publications

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“…Consistent with the findings in the present study is the clinical experience that patients may start to feel better very early after initiation of infliximab treatment (4). The statistically significant decrease in macrophage numbers is of interest in light of the earlier studies showing an association between the number of synovial tissue macrophages and clinical signs of disease activity (33)(34)(35). After 1 month, the most pronounced reduction of macrophage numbers was found in the patients with clinical improvement.…”

Section: Discussionsupporting

confidence: 90%

Tumor necrosis factor α blockade reduces the synovial cell infiltrate early after initiation of treatment, but apparently not by induction of apoptosis in synovial tissue

Smeets

Kraan

Loon

et al. 2003

Arthritis & Rheumatism

201

141

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Objective. To determine whether treatment with the chimeric anti-tumor necrosis factor ␣ antibody infliximab could reduce cellularity by the induction of apoptosis in synovial tissue.Methods. Twenty-four rheumatoid arthritis patients with active disease were randomized to receive either infliximab (3 mg/kg) (n ‫؍‬ 12) or placebo (n ‫؍‬ 12) intravenously. All patients were subjected to arthroscopic synovial biopsy directly before initiation of treatment. A second arthroscopic synovial biopsy of the same index joint was performed 48 hours after the first arthroscopy. After the second arthroscopy, the patients who had initially received placebo were also treated with infliximab in an extension study. A third arthroscopy was performed in all patients on day 28. Immunohistologic analysis was performed to characterize the cell infiltrate. In situ detection of apoptotic cells was performed by TUNEL assay and electron microscopy.Results. At 48 hours after initiation of infliximab treatment, there was a significant reduction in the number of intimal macrophages; this was not observed in the placebo group. The number of sublining macrophages, T cells, and plasma cells also tended to be decreased in infliximab-treated patients, but not in the placebo group. Of interest, we did not detect any increase in the number of apoptotic cells after infliximab treatment.Conclusion. Infliximab therapy may reduce the number of inflammatory cells in rheumatoid synovial tissue as soon as 48 hours after initiation of treatment, but apparently not by induction of apoptosis. Conceivably, decreased cell infiltration primarily results from early inhibition of cell migration.

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Section: Discussionsupporting

confidence: 90%

Tumor necrosis factor α blockade reduces the synovial cell infiltrate early after initiation of treatment, but apparently not by induction of apoptosis in synovial tissue

Smeets

Kraan

Loon

et al. 2003

Arthritis & Rheumatism

201

141

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“…115 A significant reduction in macrophages in the synovial sublining region following treatment with disease-modifying antirheumatic drugs (DMARDs), mostly methotrexate and gold, was demonstrated in another study. 116 This was particularly pronounced in those who were responding clinically by ACR criteria. Although a significant reduction in memory T cells was observed, (and this was interestingly associated with CRP reduction), memory T-cells could still be found in the synovium of patients who attained remission.…”

Section: Cellular Compositionmentioning

confidence: 99%

Synovial tissue research: a state-of-the-art review

et al. 2017

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The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis (RA). The study of synovial tissue has advanced significantly over a number of decades from arthroplasty, blind needle biopsy and more recently facilitated by arthroscopic and ultrasonographic technology that allows easier visualisation and improves the reliability of obtaining synovial biopsies. The potential for study of pathogenesis, patient stratification, discovery of biomarkers and novel targets, as well as validation of therapy, have all been progressed rapidly in the last decade, facilitated by increasingly diverse and sophisticated analytical and technological approaches. In this review we describe clinical and translational developments in the field of synovial tissue research, outlining current and novel investigative technologies, and highlight their application to advance our understanding of the aforegoing imperatives.3

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“…There is evidence of heterogeneity in RA synovial macrophages, as judged by marker expression (146)(147)(148)(149). One interpretation of the biopsy findings mentioned above (145) is that, as proposed earlier, intimal macrophages are long-lived and possibly derive from the more transient sublining population. However, it is also possible that they are independent of each other.…”

Section: Macrophage Lineage Heterogeneitymentioning

confidence: 72%

“…Interestingly, one long-term study, in which RA patients were followed up through remission and the macrophage content of synovial biopsy specimens was observed over time, showed that DMARDs reduced the numbers of both sublining and intimal macrophages (145). There is evidence of heterogeneity in RA synovial macrophages, as judged by marker expression (146)(147)(148)(149).…”

Section: Macrophage Lineage Heterogeneitymentioning

confidence: 99%

The dynamics of macrophage lineage populations in inflammatory and autoimmune diseases

Hamilton¹,

Tak²

2009

Arthritis & Rheumatism

197

183

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Treatment-induced remission in rheumatoid arthritis patients is characterized by a reduction in macrophage content of synovial biopsies

Abstract: Remission in RA patients is characterized by a predominant reduction in macrophage content of the synovial membrane, suggesting that current DMARDs may target this cell and its inflammatory mediators.

Cited by 52 publications

References 8 publications

Tumor necrosis factor α blockade reduces the synovial cell infiltrate early after initiation of treatment, but apparently not by induction of apoptosis in synovial tissue

Tumor necrosis factor α blockade reduces the synovial cell infiltrate early after initiation of treatment, but apparently not by induction of apoptosis in synovial tissue

Synovial tissue research: a state-of-the-art review

The dynamics of macrophage lineage populations in inflammatory and autoimmune diseases

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