scholarly journals Modular Analysis of Peripheral Blood Gene Expression in Rheumatoid Arthritis Captures Reproducible Gene Expression Changes in Tumor Necrosis Factor Responders

2015 ◽  
Vol 67 (2) ◽  
pp. 344-351 ◽  
Author(s):  
Michaela Oswald ◽  
Mark E. Curran ◽  
Sarah L. Lamberth ◽  
Robert M. Townsend ◽  
Jennifer D. Hamilton ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Peripheral Blood ◽  
Tumor Necrosis ◽  
Blood Gene Expression ◽  
Peripheral Blood Gene Expression ◽  
Modular Analysis ◽  
Necrosis Factor

scholarly journals Peripheral blood gene expression profiling in rheumatoid arthritis

2005 ◽  
Vol 6 (5) ◽  
pp. 388-397 ◽  
Author(s):  
F M Batliwalla ◽  
E C Baechler ◽  
X Xiao ◽  
W Li ◽  
S Balasubramanian ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Gene Expression Profiling ◽  
Peripheral Blood ◽  
Expression Profiling ◽  
Blood Gene Expression ◽  
Peripheral Blood Gene Expression

Differential Gene Expression Profiles May Differentiate Responder and Nonresponder Patients with Rheumatoid Arthritis for Methotrexate (MTX) Monotherapy and MTX plus Tumor Necrosis Factor Inhibitor Combined Therapy

2012 ◽  
Vol 39 (8) ◽  
pp. 1524-1532 ◽  
Author(s):  
RENÊ DONIZETI RIBEIRO OLIVEIRA ◽  
VANESSA FONTANA ◽  
CRISTINA MORAES JUNTA ◽  
MÁRCIA MARIA CHIQUITELLI MARQUES ◽  
CLÁUDIA MACEDO ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Differential Gene Expression ◽  
Tumor Necrosis ◽  
Expression Profiles ◽  
Combined Therapy ◽  
Gene Expression Profiles ◽  
Differential Gene ◽  
Necrosis Factor

Objective.We aimed to evaluate whether the differential gene expression profiles of patients with rheumatoid arthritis (RA) could distinguish responders from nonresponders to methotrexate (MTX) and, in the case of MTX nonresponders, responsiveness to MTX plus anti-tumor necrosis factor-α (anti-TNF) combined therapy.Methods.We evaluated 25 patients with RA taking MTX 15–20 mg/week as a monotherapy (8 responders and 17 nonresponders). All MTX nonresponders received infliximab and were reassessed after 20 weeks to evaluate their anti-TNF responsiveness using the European League Against Rheumatism response criteria. A differential gene expression analysis from peripheral blood mononuclear cells was performed in terms of hierarchical gene clustering, and an evaluation of differentially expressed genes was performed using the significance analysis of microarrays program.Results.Hierarchical gene expression clustering discriminated MTX responders from nonresponders, and MTX plus anti-TNF responders from nonresponders. The evaluation of only highly modulated genes (fold change > 1.3 or < 0.7) yielded 5 induced (4 antiapoptotic and CCL4) and 4 repressed (4 proapoptotic) genes in MTX nonresponders compared to responders. In MTX plus anti-TNF non-responders, the CCL4, CD83, and BCL2A1 genes were induced in relation to responders.Conclusion.Study of the gene expression profiles of RA peripheral blood cells permitted differentiation of responders from nonresponders to MTX and anti-TNF. Several candidate genes in MTX non-responders (CCL4, HTRA2, PRKCD, BCL2A1, CAV1, TNIP1, CASP8AP2, MXD1, and BTG2) and 3 genes in MTX plus anti-TNF nonresponders (CCL4, CD83, and BCL2A1) were identified for further study.

Tumor necrosis factor priming of peripheral blood neutrophils from rheumatoid arthritis patients

1996 ◽  
Vol 16 (4) ◽  
pp. 216-221 ◽  
Author(s):  
I. C. Kowanko ◽  
A. Ferrante ◽  
G. Clemente ◽  
P. P. Youssef ◽  
M. Smith
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Peripheral Blood ◽  
Tumor Necrosis ◽  
Blood Neutrophils ◽  
Necrosis Factor

scholarly journals Distinct single cell gene expression in peripheral blood monocytes correlates with tumor necrosis factor inhibitor treatment response groups defined by type I interferon in rheumatoid arthritis

2019 ◽  
Author(s):  
Theresa L. Wampler Muskardin ◽  
Wei Fan ◽  
Zhongbo Jin ◽  
Mark A. Jensen ◽  
Jessica M. Dorschner ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Type I ◽  
Cell Gene Expression ◽  
Response Group ◽  
Cell Gene ◽  
Α Activity ◽  
Necrosis Factor

AbstractPreviously, we demonstrated that type I IFN (IFNβ/α) activity can predict non-response to tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). In this study, we examine the biology of TNFi non-response in monocytes from RA patients. We compared single cell gene expression in purified classical (CL, n=342) and non-classical (NC, n=359) monocytes. RA patients were grouped according to their pre-TNFi IFNβ/α activity: those likely to have EULAR no response (non-response group, IFNβ/α 0 or >1.3, n=9) and those likely to have EULAR moderate or good response (response group, IFNβ/α > 0 and ≤1.3, n=6). Major differences in gene expression were apparent in principal component and unsupervised cluster analyses. CL monocytes from the non-response group were unlikely to express JAK1 and IFI27 (p <0.0001 and p 0.0005, respectively). In NC monocytes from the same group, expression of IFNAR1, IRF1, TNFA, TLR4 (p ≤0.0001 for each) and others was enriched. Interestingly, JAK1 expression was absent in CL and NC monocytes from 9 patients. This pattern strongly associated with the non-response IFNβ/α group, suggesting a major biological difference between JAK1 expressors and non-expressors. The type I IFN activity that was previously found to predict TNFi response associated with changes in gene expression in monocytes that suggest differential IFN pathway activation in RA patients who are either likely to respond or to have no response to TNFi. This work could suggest mechanisms for TNFi non-response, and potential therapeutic strategies for those patients unlikely to respond to TNFi.

Peripheral Blood Expression Profiles of Bone Morphogenetic Proteins, Tumor Necrosis Factor-superfamily Molecules, and Transcription Factor Runx2 Could Be Used as Markers of the Form of Arthritis, Disease Activity, and Therapeutic Responsiveness

2009 ◽  
Vol 37 (2) ◽  
pp. 246-256 ◽  
Author(s):  
DANKA GRCEVIC ◽  
ZRINKA JAJIC ◽  
NATAŠA KOVACIC ◽  
IVAN KREŠIMIR LUKIC ◽  
VEDRAN VELAGIC ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Peripheral Blood ◽  
Tumor Necrosis ◽  
Fas Ligand ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Roc Curve Analysis ◽  
Necrosis Factor

Objective.To assess whether different forms of arthritis and disease activity could be distinguished by peripheral blood expression profiles of bone-regulatory factors including tumor necrosis factor (TNF)-superfamily [TNF-related apoptosis-inducing ligand (TRAIL), the Fas ligand (FasL), and the ligand for herpesvirus entry mediator (LIGHT)] and bone morphogenetic protein (BMP)-family members (BMP-2, BMP-4, BMP-6) as well as osteoblast differentiation gene Runx2.Methods.Blood cells from healthy controls (n = 25) and patients at different disease stages with rheumatoid arthritis (RA; n = 49), osteoarthritis (OA; n = 17), or spondyloarthritis, including ankylosing spondylitis (AS; n = 27) or psoriatic arthritis (PsA; n = 23), were processed for quantitative polymerase chain reaction. Gene expression was assessed in comparison with control samples, correlated with clinical data of different forms of arthritis, and analyzed for discriminative efficacy between groups by receiver-operation characteristic (ROC) curves. Results were confirmed on diagnostic RA (n = 5) and AS (n = 8) samples.Results.BMP-4, BMP-6, and Runx2 expressions were significantly decreased in patients with RA and OA versus controls. Patients with RA also had decreased FasL and LIGHT expression, while patients with AS had increased Runx2 expression. Negative correlation with disease activity was found for BMP-4, FasL, and Runx2 in RA and for Runx2 in PsA, while positive correlation was found for BMP-4 in PsA. Gene expression was higher in the therapy-resistant form of AS (for BMP-4, LIGHT, and Runx2) and in methotrexate-treated patients in RA (for BMP-2 and LIGHT). ROC curve analysis confirmed discrimination between groups, particularly decreased LIGHT and Runx2 for RA and increased Runx2 for AS.Conclusion.Our study identified BMP and Runx2 as possible biomarkers of bone metabolism in several forms of arthritis, while lower FasL and LIGHT were associated with RA. Correlation between gene expression and disease activity may be clinically useful in assessing therapeutic effectiveness and disease monitoring.

scholarly journals Evaluation of Th9 lymphocytes in peripheral blood of rheumatoid arthritis patients and correlation with anti-tumor necrosis factor therapy: results from an in vitro pivotal study

Reumatismo ◽  
2016 ◽  
Vol 68 (2) ◽  
pp. 83 ◽  
Author(s):  
R. Talotta ◽  
A. Berzi ◽  
F. Atzeni ◽  
D. Dell'Acqua ◽  
P. Sarzi Puttini ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Peripheral Blood ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
T Helper ◽  
Th9 Cells ◽  
Necrosis Factor

The aim of this study was to determine the prevalence of T helper 9 (Th9) lymphocytes in rheumatoid arthritis (RA) patients and to identify a possible association between the percentage of Th9 and the discontinuation of a biological treatment with an anti-tumor necrosis factor (TNF) (infliximab). We collected peripheral blood mononuclear cells (PBMCs) from 55 consecutive RA outpatients and 10 healthy controls. Among RA patients, 15 were not receiving any immunosuppressive drug, 20 were successfully treated with infliximab and 20 discontinued infliximab because of adverse events or inefficacy and were treated with other biological agents. PBMCs were cultured with/without infliximab 50 mg/L for 18 h, and the percentage of Th9 cells was assessed by means of flow cytometry. Th9 lymphocytes were identified as interferon gamma, interleukin (IL)4-, IL17-, IL9-secreting cluster of differentiation 4 (CD4)+ T cells. Cytometric analysis revealed no significant decrease in the percentage of Th9 cells after infliximab exposure in any of the groups, although it was lower in healthy controls than RA patients either before and after the infliximab stimulation assay. Th9 cells are IL-9-secreting T helper lymphocytes whose role in RA is still poorly known. IL-9 levels are increased in RA patients, in whom this cytokine plays a crucial role. Th9 cells are the major producers of IL-9, and their prevalence is higher in RA patients than in healthy subjects; however our experiment <em>in vitro</em> does not demonstrate an association between Th9 lymphocytes and the response to infliximab. Further studies are required to evaluate the real involvement of Th9 population in the immunogenicity of anti-TNF agents.

Treatment with monoclonal anti-tumor necrosis factor ? antibody results in an accumulation of Th1 CD4+ T cells in the peripheral blood of patients with rheumatoid arthritis

1999 ◽  
Vol 42 (10) ◽  
pp. 2166-2173 ◽  
Author(s):  
Madelon M. Maurice ◽  
Wiebo L. Van Der Graaff ◽  
Angela Leow ◽  
Ferdinand C. Breedveld ◽  
Ren� A. W. Van Lier ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Tumor Necrosis Factor ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Tumor Necrosis ◽  
Necrosis Factor
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