Correlation of a multi-cytokine panel with clinical disease activity in patients with rheumatoid arthritis

Milman, Nataliya; Karsh, Jacob; Booth, Ronald A.

doi:10.1016/j.clinbiochem.2010.07.012

Cited by 51 publications

(35 citation statements)

References 32 publications

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“…Both DAS28 score and ESR have been previously correlated with the serum levels of pro-inflammatory cytokine IL-6. 31 Moreover, IL-6 has been shown to induce expression of miR-451 in dendritic cells. 32 To test whether an increased expression of miR-451 in T cells could be related to an increased presence of IL-6, we measured IL-6 levels in the sera of RA patients.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive analysis of miRNA expression in T-cell subsets of rheumatoid arthritis patients reveals defined signatures of naive and memory Tregs

et al. 2014

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Disturbed expression of microRNAs (miRNAs) in regulatory T cells (Tregs) leads to development of autoimmunity in experimental mouse models. However, the miRNA expression signature characterizing Tregs of autoimmune diseases, such as rheumatoid arthritis (RA) has not been determined yet. In this study, we have used a microarray approach to comprehensively analyze miRNA expression signatures of both naive Tregs (CD4+CD45RO-CD25++) and memory Tregs (CD4+CD45RO+CD25+++), as well as conventional naive (CD4+CD45RO−CD25−) and memory (CD4+CD45RO+CD25−) T cells (Tconvs) derived from peripheral blood of RA patients and matched healthy controls. Differential expression of selected miRNAs was validated by TaqMan-based quantitative reverse transcription-PCR. We found a positive correlation between increased expression of miR-451 in T cells of RA patients and disease activity score (DAS28), erythrocyte sedimentation rate levels and serum levels of interleukin-6. Moreover, we found characteristic, disease- and treatment-independent, global miRNA expression signatures defining naive Tregs, memory Tregs, naive Tconvs and memory Tconvs. The analysis allowed us to define miRNAs characteristic for a general naive phenotype (for example, miR-92a) and a general memory phenotype (for example, miR-21, miR-155). Importantly, the analysis allowed us to define miRNAs that are specifically expressed in both naive and memory Tregs, defining as such miRNA signature characterizing the Treg phenotype (that is, miR-146a, miR-3162, miR-1202, miR-1246 and miR-4281).

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Section: Resultsmentioning

confidence: 99%

Comprehensive analysis of miRNA expression in T-cell subsets of rheumatoid arthritis patients reveals defined signatures of naive and memory Tregs

et al. 2014

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“…Markers such as CRP [16], haptoglobin, apolipoprotein C3 [17], and ENRAGE [18] have been associated with the early, acute phase responses that occur in RA. Additionally, Charles-Schoeman and colleagues [17] showed that patients with RA with proinflammatory high-density lipoprotein (HDL) exhibit increases in haptoglobin and apolipoprotein levels as compared with patients with anti-inflammatory HDL.…”

Section: Discussionmentioning

confidence: 99%

Association of serum markers with improvement in clinical response measures after treatment with golimumab in patients with active rheumatoid arthritis despite receiving methotrexate: results from the GO-FORWARD study

et al. 2010

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IntroductionThe goal of this study was to identify serum markers that are modulated by treatment with golimumab with or without methotrexate (MTX) and are associated with clinical response.MethodsSera were collected at weeks 0 and 4 from a total of 336 patients (training dataset, n = 100; test dataset, n = 236) from the GO-FORWARD study of patients with active rheumatoid arthritis despite MTX. Patients were randomly assigned to receive placebo plus MTX; golimumab, 100 mg plus placebo; golimumab, 50 mg plus MTX; or golimumab, 100 mg plus MTX. Subcutaneous injections were administered every 4 weeks. Samples were tested for select inflammatory, bone, and cartilage markers and for protein profiling using multianalyte profiles.ResultsTreatment with golimumab with or without MTX resulted in significant decreases in a variety of serum proteins at week 4 as compared with placebo plus MTX. The American College of Rheumatology (ACR) 20, ACR 50, and Disease Activity Score (DAS) 28 responders showed a distinct biomarker profile compared with nonresponding patients.ConclusionsACR 20 and ACR 50 responders among the golimumab/golimumab + MTX-treated patients had a distinct change from baseline to week 4 in serum protein profile as compared with nonresponders. Some of these changed markers were also associated with multiple clinical response measures and improvement in outcome measures in golimumab/golimumab + MTX-treated patients. Although the positive and negative predictive values of the panel of markers were modest, they were stronger than C-reactive protein alone in predicting clinical response to golimumab.Trial registrationhttp://ClinicalTrials.gov identification number: NCT00264550.

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“…The M1 Mɸ phenotype is induced by interferon-γ (IFNγ) in combination with either lipopolysaccharide (LPS) or TNFα. IFNγ is highly expressed in RA synovial tissue and its levels significantly correlate with disease severity (Milman et al, 2010). Exposure to INFγ increases the response of Mɸ exposed to other stimuli by either upregulating pro-inflammatory cytokines, like TNFα, or downregulating anti-inflammatory cytokines, like IL-10 (Erwig et al, 1998; Wallet et al, 2010).…”

Section: What Regulators In Synovial Inflammation Could Potentially Imentioning

confidence: 99%

Macrophages in Synovial Inflammation

Kennedy¹,

Fearon²,

Veale³

et al. 2011

Front. Immun.

156

123

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Synovial macrophages are one of the resident cell types in synovial tissue and while they remain relatively quiescent in the healthy joint, they become activated in the inflamed joint and, along with infiltrating monocytes/macrophages, regulate secretion of pro-inflammatory cytokines and enzymes involved in driving the inflammatory response and joint destruction. Synovial macrophages are positioned throughout the sub-lining layer and lining layer at the cartilage–pannus junction and mediate articular destruction. Sub-lining macrophages are now also considered as the most reliable biomarker for disease severity and response to therapy in rheumatoid arthritis (RA). There is a growing understanding of the molecular drivers of inflammation and an appreciation that the resolution of inflammation is an active process rather than a passive return to homeostasis, and this has implications for our understanding of the role of macrophages in inflammation. Macrophage phenotype determines the cytokine secretion profile and tissue destruction capabilities of these cells. Whereas inflammatory synovial macrophages have not yet been classified into one phenotype or another it is widely known that TNFα and IL-l, characteristically released by M1 macrophages, are abundant in RA while IL-10 activity, characteristic of M2 macrophages, is somewhat diminished. Here we will briefly review our current understanding of macrophages and macrophage polarization in RA as well as the elements implicated in controlling polarization, such as cytokines and transcription factors like NFκB, IRFs and NR4A, and pro-resolving factors, such as LXA4 and other lipid mediators which may promote a non-inflammatory, pro-resolving phenotype, and may represent a novel therapeutic paradigm.

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Correlation of a multi-cytokine panel with clinical disease activity in patients with rheumatoid arthritis

Cited by 51 publications

References 32 publications

Comprehensive analysis of miRNA expression in T-cell subsets of rheumatoid arthritis patients reveals defined signatures of naive and memory Tregs

Comprehensive analysis of miRNA expression in T-cell subsets of rheumatoid arthritis patients reveals defined signatures of naive and memory Tregs

Association of serum markers with improvement in clinical response measures after treatment with golimumab in patients with active rheumatoid arthritis despite receiving methotrexate: results from the GO-FORWARD study

Macrophages in Synovial Inflammation

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