Effects of pulse methylprednisolone on inflammatory mediators in peripheral blood, synovial fluid, and synovial membrane in rheumatoid arthritis

Youssef, Peter; Haynes, David R.; Triantafillou, Sophie; Parker, Angela; Gamble, Jennifer R.; Roberts‐Thomson, Peter; Ahern, Michael; Smith, Malcolm D.

doi:10.1002/art.1780400807

Cited by 105 publications

(50 citation statements)

References 35 publications

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“…However, the current study is limited in its capacity to evaluate the complete implication of DCs in the pathogenesis of RA: the small number of patients, variability in patient's factors at study entry (disease duration, previous DMARD treatment [46,47]). It has to be continued in order to allow statistical correlations and to prove the importance of adhesion and co-stimulatory molecules expression on DCs as targets for future immunotherapies.…”

Section: Discussionmentioning

confidence: 99%

Co‐stimulatory and adhesion molecules of dendritic cells in rheumatoid arthritis

Bălănescu

Radu

Nat

et al. 2002

J Cellular Molecular Medi

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Dendritic cells (DCs) in the rheumatoid arthritis (RA) joint mediate the immunopathological process and act as a potent antigen presenting cell. We compared the expression of co‐stimulatory and adhesion molecules on DCs in RA patients versus controls with traumatic joint lesions and evalulated the correlation between the immunophenotypical presentation of DCs and the clinical status of the disease. Samples of peripheral venous blood, synovial fluid (SF) and synovial tissue (ST) were obtained from 10 patients with RA at the time of hip or knee replacement and from 9 control patients with knee arthroscopy for traumatic lesions. Clinical status was appreciated using the DAS28 score. Blood, SF and dissociated ST cell populations were separated by centrifugation and analyzed by flow cytometry. Cells phenotypes were identified using three‐color flow cytometry analysis for the following receptors HLA‐DR, CD80, CD83, CD86, CD11c, CD18, CD54, CD58, CD3, CD4, CD8, CD19, CD20, CD14, CD16, CD56. HLA‐DR molecules, co‐stimulatory receptors CD80, CD86, CD83 and adhesion molecules CD18, CD11c, CD54, CD58, were analyzed by two‐color immunofluorescence microscopy on ST serial sections. In patients with active RA (DAS28>5.1) we found a highly differentiated subpopulation of DCs in the ST and SF that expressed an activated phenotype (HLA‐DR, CD86+, CD80+, CD83+, CD11c+, CD54+, CD58+). No differences were found between circulating DCs from RA patients and control patients. Our data suggest an interrelationship between clinical outcome and the immunophenotypical presentation of DCs. Clinical active RA (DAS28>5.1) is associated with high incidence of activated DCs population in the ST and SF as demonstrated by expression of adhesion and co‐stimulatory molecules.

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Section: Discussionmentioning

confidence: 99%

Co‐stimulatory and adhesion molecules of dendritic cells in rheumatoid arthritis

Bălănescu

Radu

Nat

et al. 2002

J Cellular Molecular Medi

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“…Sections (7 m) were mounted on Superfrost slides, and immunohistochemistry and scoring of the staining were performed as described previously (35,36).…”

Section: Methodsmentioning

confidence: 99%

“…Annealing temperatures were 55°C for Fc␥RI and GAPDH, 60°C for Fc␥RIIa and Fc␥RIIb, and 62°C for Fc␥RIII. The PCR reaction was stopped after 20,23,26,29,32,35,38,41, and 44 cycles at the very end of the extension phase (72°C), and 5-l samples were obtained.…”

Section: Methodsmentioning

confidence: 99%

Increased expression of Fcγ receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor α and matrix metalloproteinase

Blom¹,

Radstake²,

Holthuysen³

et al. 2003

Arthritis & Rheumatism

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Objective. To evaluate Fc␥ receptor (Fc␥R) expression on synovial macrophages from rheumatoid arthritis (RA) patients and to determine whether this expression correlates with the production of the proinflammatory cytokines tumor necrosis factor ␣ (TNF␣), interleukin-1␤ (IL-1␤), IL-12, and matrix metalloproteinase 1 (MMP-1). We also sought to determine whether mature macrophages from RA patients express aberrant levels of Fc␥RI, Fc␥RII, and Fc␥RIII, and to determine the production of inflammatory mediators after immune complex (IC) stimulation.Methods. Immunohistochemistry was performed on cryostat sections of synovial biopsy specimens obtained from 27 RA patients and 5 controls. Fc␥R I, II, and III were detected, as well as the proinflammatory mediators IL-1, TNF␣, IL-12, and MMP-1. Monocytes were isolated from the blood of 10 RA patients and 10 healthy controls and cultured for 7 days with macrophage colony-stimulating factor to obtain macrophages. Using fluorescence-activated cell sorting, the expression of Fc␥RI, Fc␥RII, and Fc␥RIII was determined. On day 7, macrophages were stimulated with heat-aggregated gamma globulins (HAGGs) for 24 hours. Production of cytokines was measured using enzyme-linked immunosorbent assay, and production of gelatinases/ collagenases was measured by degradation of fluorescent gelatin.Results. Immunohistochemistry showed higher Fc␥RII and Fc␥RIII expression in RA synovium than in controls. Fc␥RII and Fc␥RIII, but not Fc␥RI, were highly correlated with the number of synovial macrophages. Consistent with this, TNF␣ expression correlated positively with Fc␥RIII expression. Moreover, MMP-1 expression strongly correlated with Fc␥R I, II, and III expression. Mature macrophages from RA patients showed significantly enhanced expression of Fc␥RII and Fc␥RIII compared with controls. Twentyfour hours after stimulation of RA macrophages with HAGGs, significantly higher production of TNF␣ and gelatinase/collagenase was measured.Conclusion. RA synovium and mature RA macrophages express significantly elevated levels of Fc␥RII and Fc␥RIII, resulting in much higher production of TNF␣ and gelatinase/collagenase after IC stimulation. These data suggest that disturbed expression of Fc␥R on mature synovial macrophages is involved in the pathology of RA.

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“…Sixty-one outpatients presented for management of RA to a specialist clinic. Of these, 20 had a flare of their disease, as previously defined (40), upon study entry. The Health Assessment Questionnaire (HAQ) (41) was administered to these 20 patients and to the HSCT group before treatment.…”

Section: Patient Cohort Characteristicsmentioning

confidence: 99%

Serum macrophage inhibitory cytokine 1 in rheumatoid arthritis: A potential marker of erosive joint destruction

Brown

Moore

Johnen

et al. 2007

Arthritis & Rheumatism

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Objective. The transforming growth factor ␤ superfamily member macrophage inhibitory cytokine 1 (MIC-1) is expressed upon macrophage activation, regulated by the p53 pathway, and linked to clinical events in atherosclerosis and cancer. Since rheumatoid arthritis (RA) shares similar etiopathologic mechanisms with the above diseases, we sought to determine the clinical utility of determining MIC-1 serum levels and MIC-1 genotype in the management of RA.Methods. Ninety-one RA patients were recruited. Serum was collected from 83 of these patients and synovial biopsy samples were collected from the remaining 8 patients. Of the 83 patients from whom serum was collected, 61 were treated on an outpatient basis (defined as having nonsevere disease), and 22 patients went on to undergo hemopoietic stem cell transplantation (HSCT) (defined as having severe disease).Results. Serum levels of MIC-1 were higher in RA patients and reflected disease severity independently of classic disease markers. MIC-1 was detected in rheumatoid synovial specimens, and allelic variation of MIC-1 was associated with earlier erosive disease and severe treatment-resistant chronic RA. Additionally, algorithms including serum and/or allelic variation in MIC-1 predicted response to HSCT, the presence of severe disease, and joint erosions.Conclusion. Determination of serum levels of MIC-1 and MIC-1 genotype may be clinically useful in the management of RA as well as in selection of patients for HSCT, since they predict disease course and response to therapy. The data indicate a potential role for MIC-1 in RA pathogenesis. These results warrant larger prospective studies to fully delineate and confirm a role for MIC-1 genotyping and serum estimation in patient selection for HSCT and in the management of RA.

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Effects of pulse methylprednisolone on inflammatory mediators in peripheral blood, synovial fluid, and synovial membrane in rheumatoid arthritis

Cited by 105 publications

References 35 publications

Co‐stimulatory and adhesion molecules of dendritic cells in rheumatoid arthritis

Co‐stimulatory and adhesion molecules of dendritic cells in rheumatoid arthritis

Increased expression of Fcγ receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor α and matrix metalloproteinase

Serum macrophage inhibitory cytokine 1 in rheumatoid arthritis: A potential marker of erosive joint destruction

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