scholarly journals Association between a low baseline level of gene expression of energy metabolism in the blood and the development of clinical remission in response to tofacitinib therapy in patients with rheumatoid arthritis

2021 ◽  
Vol 15 (3) ◽  
pp. 20-26
Author(s):  
E. V. Chetina ◽  
A. M. Satybaldyev ◽  
G. A. Markova ◽  
E. Yu. Samarkina ◽  
M. V. Cherkasova
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Disease Activity ◽  
Peripheral Blood ◽  
Clinical Remission ◽  
Energy Generation ◽  
Janus Kinase ◽  
Control Subjects ◽  
Expression Of Genes ◽  
Lower Baseline

Background. Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, characterized by erosive arthritis (synovitis) and systemic inflammation. Janus kinase (JAK) inhibitors (JAKi) are small molecules that block major signal pathways of many cytokines a growth factors, associated with RA. Identification of patients sensitive to JAKi before treatment could significantly improve therapy outcomes. Currently it is not possible to predict JAKi efficacy in every patient, while some patients are non-responsive to the drug, other develop adverse effects. JAKi effect in RA patients has been recently associated with alterations in mitochondrial function and ATP production. Therefore, we hypothesized that baseline metabolic status of RA patients prior to drug administration can predict the therapeutic outcome.Objective: to investigate the predictive value of baseline expression of genes involved in energy generation in the blood of RA patients, for treatment response to JAKi.Patients and methods. We examined peripheral blood of 28 RA patients aged 52.2±15.6 years, average disease duration 3.5 years (range 0.6–19), treated with Tofacitinib (TOFA, 5–10 mg twice a day) during three months and 26 healthy age-matched control subjects. Clinical response was assessed by disease activity score (DAS28-ESR), immunological status by measurements of serum levels of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), and C-reactive protein (CRP). Gene expression was assessed in peripheral blood cells by realtime reverse-transcription polymerase chain reaction (RT-PCR). At baseline all patients had Steinbrocker radiographic stage II–III. Most patients (85.7%) were ACPA and RF positive. Thirteen patients had medium, others – high RA activity.Results and discussion. JAKi treatment significantly decreased the inflammatory disease activity according to DAS28. At the end of the study 17 patients demonstrated moderate disease activity (3.2<DAS28<5.1), 4 patients retained high disease activity while 7, attained remission (DAS28 <2.6). Disease remission, achieved on TOFA treatment, was accompanied by significant decrease in CRP and the number of swollen and tender joints. ESR values were not changed significantly. Gene expression analysis revealed that RA patients, which attained clinical remission after TOFA treatment, demonstrated significantly lower baseline expression of genes associated with glycolysis (pyruvate kinase, PKM2) and oxidative phosphorylation (succinate dehydrogenase, SDHB) compared to other examined RA patients, but higher expression of the abovementioned genes compared to control subjects. Moreover, RA patients who attained clinical remission demonstrated a trend to increase of these gene expressions within follow-up period, while in the rest of patients these gene expression was tending to downregulate.Conclusion. Clinical remission in RA patients treated with JAKi is associated with significantly lower baseline expression of genes associated with energy generation pathways (PKM2 and SDHB) compared to other examined subjects.

scholarly journals Putative Association between Low Baseline Gene Expression in the Peripheral Blood and Clinical Remission in Rheumatoid Arthritis Patients Treated with Tofacitinib

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1385
Author(s):  
Elena V. Tchetina ◽  
Azamat M. Satybaldyev ◽  
Galina A. Markova ◽  
Elena Yu. Samarkina ◽  
Aleksandr M. Lila
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Disease Activity ◽  
Peripheral Blood ◽  
Clinical Remission ◽  
Energy Generation ◽  
Serum Levels ◽  
Das28 Score ◽  
Expression Of Genes ◽  
Before And After

We investigated the importance of the baseline expression of genes involved in energy generation, as prognostic biomarkers of the treatment response to tofacitinib in patients with rheumatoid arthritis (RA). Peripheral blood samples were obtained from 28 patients with RA who received 3 months of tofacitinib therapy from 26 healthy controls. Clinical response was evaluated based on the disease activity score, the erythrocyte sedimentation rate (DAS28-ESR), and the serum levels of ACPA, RF, CRP, and ESR. Clinical remission was assessed based on DAS28 score <2.6. Protein concentrations were measured using ELISA. Total RNA isolated from whole blood was used for gene expression analysis using quantitative RT-PCR. All patients were diagnosed with Steinbrocker’s radiographic stage II-III at baseline, and most showed erosive arthritis with ACPA and RF positivity. Tofacitinib treatment significantly decreased the disease activity. Upon study completion, seven patients showed remission. Before and after TOFA therapy, a significantly higher expression of succinate dehydrogenase and pyruvate kinase genes was observed in all the examined patients compared to healthy subjects. However, the pre-therapy expression of these genes and corresponding proteins was significantly (p ≤ 0.05) lower in patients who showed remission than in other patients with RA. Moreover, we observed that, during follow-up, patients who developed remission showed an increasing trend in the expression of the examined genes, whereas the others showed some decreases in gene expression, although this was not statistically significant. We concluded that, compared with RA patients maintaining persistent moderate or high disease activity, those with clinical remission following tofacitinib treatment showed a significantly lower baseline expression of genes involved in energy generation.

scholarly journals POS0099 CLINICAL REMISSION IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TOFACITINIB IS ASSOCIATED WITH LOW BASELINE EXPRESSION OF GENES RELATED TO ENERGY METABOLISM AND WITH CELLULAR CAPACITY OF THEIR UPREGULATION DURING FOLLOW-UP

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 259.3-260
Author(s):  
E. Tchetina ◽  
A. Satybaldyev ◽  
G. Markova
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Phosphorylation ◽  
Disease Activity ◽  
Mitochondrial Function ◽  
Clinical Remission ◽  
Gene Expressions ◽  
Erosive Arthritis ◽  
Expression Of Genes ◽  
Lower Baseline

Background:Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, which is characterized by erosive arthritis (synovitis) and systemic inflammation. Tofacitinib (TFCN) is a small molecule Janus kinase (JAK) inhibitor that targets JAK1/JAK3. Identification of patients sensitive to TFCN before treatment could significantly improve therapy outcome. Presently it is not possible to predict TFCN efficacy in every patient while some patients are non-responsive to the drug that may produce adverse effects. TFCN function in RA patients has been recently associated with alterations in bioenergetics, mitochondrial function, and ATP production [1]. Therefore, we hypothesized that baseline metabolic status of RA patients prior to drug administration can predict the therapeutic outcome.Objectives:To investigate the importance of baseline expression of genes involved in energy generation in RA patients, which could serve prognostic biomarkers for treatment response to tofacitinib.Methods:Peripheral blood of 28 RA patients aged 52.2±15.6 years old, average disease duration 3.5 years (range 0.6-19) treated with TFCN (5-10 mg twice a day) during three months and 26 healthy age-matched control subjects were examined. Clinical response was assessed by disease activity score (DAS28-ESR), serum levels of ACPA antibodies, rheumatoid factor (RF), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Clinical remission was assessed according to ACR criteria and DAS28 (DAS28 <2.6). Protein concentrations were measured using ELISA. Total RNA was isolated and used in gene expression studies performed with quantitative real-time RT-PCR.Results:All of the patients were Steinbrocker’s radiographic stage II-III at baseline. The majority of patients demonstrated erosive arthritis (23 out of 28), they were ACPA- (25 out of 28) and RF- (24 out of 28) positive. TFCN treatment significantly decreased the disease activity according to DAS28. At the end of the study the majority of patients demonstrated moderate disease activity (3.2< DAS28 <5.1), four patients retained high disease activity while 8, attained remission (DAS28 <2.6). This was accompanied by significant decrease in CRP and the number of swollen and tender joints. ESR values were not changed significantly. Gene and protein expression analysis revealed that RA patients, which attained clinical remission after TFCN treatment demonstrated significantly lower baseline expression of genes associated with glycolysis (pyruvate kinase), oxidative phosphorylation (succinate dehydrogenase and uncoupling protein (UCP) 2) compared to other examined RA patients and control subjects. Moreover, these gene expressions increased in RA patients who attained clinical remission in the course of follow-up while in refractory for TFCN treatment patients these gene expressions were tending to downregulate.Conclusion:Clinical remission attainment in RA patients treated with tofacitinib is associated with lower baseline expression of genes associated with energy generation pathways (pyruvate kinase, succinate dehydrogenase, and UCP2) compared to other examined subjects. Non-responsiveness to tofacitinib is accompanied by high baseline expression of genes related to glycolysis and oxidative phosphorylation compared to controls.References:[1]McGarry et al. JAK/STAT Blockade Alters Synovial Bioenergetics, Mitochondrial Function, and Proinflammatory Mediators in Rheumatoid Arthritis. Arthritis Rheumatol, 2018; 70:1959.Acknowledgements:Russian Ministry of Education and Science (Project No. AAAA-A19-11-9021190145-2 to EVT).Disclosure of Interests:None declared

scholarly journals Metabolic aspects of clinical remission prediction from baseline blood gene expression in patients with rheumatoid arthritis treated with methotrexate

2019 ◽  
Vol 13 (2) ◽  
pp. 47-54
Author(s):  
E. V. Chetina ◽  
N. V. Demidova ◽  
G. A. Markova
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Disease Activity ◽  
Clinical Remission ◽  
Structural Changes ◽  
Caspase 3 ◽  
Unknown Etiology ◽  
Control Group ◽  
Healthy Individuals ◽  
Number Of Patients

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, which is characterized by chronic erosive arthritis (synovitis) and systemic inflammation of the viscera. Methotrexate (MTX) is the drug of choice for RA treatment. However, it is currently impossible to predict the efficacy of MTX in a particular patient; the drug fails to produce the desired effect or causes adverse reactions in a considerable number of patients. The identification of patients who are responsive to MTX could significantly improve the results of therapy.Objective: to investigate the specific features of baseline (pretreatment) expression of genes responsible for major metabolic and energy production pathways in RA patients with different disease activity and to identify the genes, the baseline expression of which could serve as a predictor for remission attainment.Patients and methods. Blood from 40 RA patients (mean age 47.5 years; mean disease duration 7.9 weeks) who had not previously received MTX and 26 healthy donors (mean age 45.1 years). All the patients had used MTX (15 mg/week) for 2 years. Clinical response was evaluated by DAS28 and the serum levels of anti-cyclic citrullinated peptide antibodies, C-reactive protein, and rheumatoid factor. Remission was diagnosed according to ACR/EULAR and DAS28 (DAS28 <2.6). Joint structural changes were radiographically evaluated. Gene expression was determined in peripheral blood cells by real-time reverse transcriptase-polymerase chain reaction. A control group consisted of 26 randomly recruited gender- and sex-matched patients without autoimmune diseases and a family history.Results and discussion. MTX treatment significantly decreased disease activity according to DAS28. At the end of the investigation, the majority of patients had moderate disease activity (3.2≤ DAS28 ≤5.1), 4 had high disease activity, while 12 attained remission (DAS28 <2.6). Gene expression analysis showed that RA patients who had achieved clinical remission after MTX therapy displayed higher baseline expression of the genes associated with glycolysis (Glut1, PKM), inflammation (TNF-α), autophagy (ULK1), apoptosis (caspase 3, p21), and hypoxia (HIF1α), compared with patients who had not attained remission and with healthy individuals. In addition, in patients who had achieved remission, the baseline expression of the CD1 gene was significantly higher than in healthy individuals, while in the remaining patients the expression of this gene was significantly lower than in the controls. While the disease activity remained high, the baseline expression of the p21, caspase 3, TGFβ1, and RUNX2 genes was significantly lower than in healthy individuals and other patients with RA.Conclusion. Remission achievement in RA patients who had not previously received MTX was associated with higher baseline (pretreatment) gene expression associated with glycolytic activity, inflammation, autophagy, apoptosis, and hypoxia compared with patients who failed to attain remission. Elevated baseline expression of the CD1 gene compared with that in healthy individuals may serve as a predictor of sensitivity to MT therapy. 

Evaluation of Toll-like Receptor 2 Gene Expression in Rheumatoid Arthritis and Correlation with the Disease Activity

2019 ◽  
Vol 13 (2) ◽  
pp. 140-148
Author(s):  
Mai Nasser ◽  
Noha M. Hazem ◽  
Amany Atwa ◽  
Amina Baiomy
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
Mrna Expression ◽  
Disease Activity Score ◽  
Activity Score ◽  
Tlr2 Expression ◽  
Positive Correlation ◽  
Tlr2 Mrna

Background: Rheumatoid Arthritis (RA) is an autoimmune, chronic, and systematic disease. It affects joints and bones. The exact etiology of RA is still unclear. Varied genetic and environmental factors have been associated with the increased risk for RA. Overactivation of Toll-Like Receptors (TLRs) could initiate the development of autoimmune diseases including RA. Objective: The aim of the study was to evaluate TLR2 gene expression in rheumatoid arthritis patients and investigate its correlation with the disease activity. Materials and Methods: This study included 60 patients and 20 healthy individuals. The patients were diagnosed with RA according to the 2010 American College of Rheumatology/ European League Against Rheumatism criteria (ACR/EULAR). All included subjects did not have any joint disorders and /or autoimmune diseases. RA disease activity was determined by the disease activity score of 28 joints. Whole blood was collected from all participants. Total RNA extraction was done. TLR2 mRNA expression was assessed by reverse transcription-PCR (RT-PCR). Results: TLR2 mRNA expression was found to be significantly higher in RA patients compared to healthy controls. Also, a strong positive correlation was found between TLR2 expression level and the disease activity score. A non significant positive correlation was found between TLR2 expression and serum Rheumatoid Factor (RF) level. Conclusion: TLR2 pathway may have an important role in RA pathogenesis and could be a new biomarker for diagnosis and monitoring disease activity.

scholarly journals Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression

2021 ◽  
Vol 22 (3) ◽  
pp. 1022
Author(s):  
Tatyana P. Makalish ◽  
Ilya O. Golovkin ◽  
Volodymyr V. Oberemok ◽  
Kateryna V. Laikova ◽  
Zenure Z. Temirova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Rat Model ◽  
Peripheral Blood ◽  
Antisense Oligonucleotide ◽  
Joint Inflammation ◽  
Blood Concentrations ◽  
Tnf Α ◽  
Effective Drugs ◽  
First Time

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund’s adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.

scholarly journals AB0337 TOFACITINIB MONOTHERAPY OR COMBINED WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS SHOW SIMILAR RETENTION OVER FOUR YEARS. REPORT FROM RHUMADATA ®

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1467.1-1467
Author(s):  
D. Choquette ◽  
L. Bessette ◽  
L. Choquette Sauvageau ◽  
I. Ferdinand ◽  
B. Haraoui ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Real World ◽  
Treatment Initiation ◽  
Retention Rate ◽  
Janus Kinase ◽  
P Value ◽  
Research Support ◽  
Medication Discontinuation ◽  
Kaplan Meier

Background:Since the introduction of biologic agents around the turn of the century, the scientific evidence shows that the majority of agents, independent of the therapeutic target, have a better outcome when used in combination with methotrexate (MTX). In 2014, tofacitinib (TOFA), an agent targeting Janus kinase 1 and 3, has reached the Canadian market with data showing that the combination with MTX may not be necessary [1,2].Objectives:To evaluate the efficacy and retention rate of TOFA in real-world patients with rheumatoid arthritis (RA).Methods:Two cohorts of patients prescribed TOFA was created. The first cohort was formed of patients who were receiving MTX concomitantly with TOFA (COMBO) and the other of patients using TOFA in monotherapy (MONO). MONO patients either never use MTX or were prescribed MTX post-TOFA initiation for at most 20% of the time they were on TOFA. COMBO patients received MTX at the time of TOFA initiation or were prescribed MTX post-TOFA initiation for at least 80% of the time. For all those patients, baseline demographic data definitions. Disease activity score and HAQ-DI were compared from the initiation of TOFA to the last visit. Time to medication discontinuation was extracted, and survival was estimated using Kaplan-Meier calculation for MONO and COMBO cohorts.Results:Overall, 194 patients were selected. Most were women (83%) on average younger than the men (men: 62.6 ± 11.0 years vs. women: 56.9 ± 12.1 years, p-value=0.0130). The patient’s assessments of global disease activity, pain and fatigue were respectively 5.0 ± 2.7, 5.2 ± 2.9, 5.1 ± 3.1 in the COMBO group and 6.2 ± 2.5, 6.5 ± 2.6, 6.3 ± 2.8 in the MONO group all differences being significant across groups. HAQ-DI at treatment initiation was 1.3 ± 0.7 and 1.5 ± 0.7 in the COMBO and MONO groups, respectively, p-value=0.0858. Similarly, the SDAI score at treatment initiation was 23.9 ± 9.4 and 25.2 ± 11.5, p-value=0.5546. Average changes in SDAI were -13.4 ± 15.5 (COMBO) and -8.9 ± 13.5 (MONO), p-value=0.1515, and changes in HAQ -0.21 ± 0.63 and -0.26 ± 0.74, p-value 0.6112. At treatment initiation, DAS28(4)ESR were 4.4 ± 1.4 (COMBO) and 4.6 ± 1.3 (MONO), p-value 0.5815, with respective average changes of -1.06 ± 2.07 and -0.70 ± 1.96, p-value=0.2852. The Kaplan-Meier analysis demonstrated that the COMBO and MONO retention curves were not statistically different (log-rank p-value=0.9318).Conclusion:Sustainability of TOFA in MONO or COMBO are not statistically different as are the changes in DAS28(4)ESR and SDAI. Despite this result, some patients may still benefit from combination with MTX.References:[1]Product Monograph - XELJANZ ® (tofacitinib) tablets for oral administration Initial U.S. Approval: 2012.[2] Reed GW, Gerber RA, Shan Y, et al. Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors as Monotherapy and Combination Therapy for Treatment of Rheumatoid Arthritis [published online ahead of print, 2019 Nov 9].Rheumatol Ther. 2019;6(4):573–586. doi:10.1007/s40744-019-00177-4.Disclosure of Interests:Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Loïc Choquette Sauvageau: None declared, Isabelle Ferdinand Consultant of: Pfizer, Abbvie, Amgen, Novartis, Speakers bureau: Pfizer, Amgen, Boulos Haraoui Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, and UCB, Consultant of: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Merck, Pfizer, Roche, and UCB, Speakers bureau: Pfizer, Speakers bureau: Amgen, BMS, Janssen, Pfizer, and UCB, Frédéric Massicotte Consultant of: Abbvie, Janssen, Lilly, Pfizer, Speakers bureau: Janssen, Jean-Pierre Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica, Speakers bureau: TRB Chemedica and Mylan, Jean-Pierre Raynauld Consultant of: ArthroLab Inc., Marie-Anaïs Rémillard Consultant of: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Paid instructor for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Diane Sauvageau: None declared, Édith Villeneuve Consultant of: Abbvie, Amgen, BMS, Celgene, Pfizer, Roche, Sanofi-Genzyme,UCB, Paid instructor for: Abbvie, Speakers bureau: AbbVie, BMS, Pfizer, Roche, Louis Coupal: None declared

Patients with Rheumatoid Arthritis in Clinical Remission Manifest Persistent Joint Inflammation on Histology and Imaging Studies

2014 ◽  
Vol 41 (11) ◽  
pp. 2153-2160 ◽  
Author(s):  
Allen Anandarajah ◽  
Ralf Thiele ◽  
Ellen Giampoli ◽  
Johnny Monu ◽  
Gwy-Suk Seo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Clinical Remission ◽  
Severe Disease ◽  
Joint Inflammation ◽  
Imaging Studies ◽  
American College Of Rheumatology ◽  
Remission Criteria ◽  
Magnetic Resonance Imaging Mri ◽  
Active Inflammation

Objective.The purpose of our study was to test the hypothesis that synovitis on magnetic resonance imaging (MRI) and ultrasound (US) observed in patients with rheumatoid arthritis (RA) who meet remission criteria reflects active inflammation on histopathology.Methods.We analyzed 15 synovial specimens obtained during surgical procedures from 14 patients with RA in clinical remission as defined by the American College of Rheumatology criteria. Histological specimens were scored for hyperplasia of synovial lining and synovial stroma, inflammation, lymphoid follicles, and vascularity. The histology scores were classified as minimal, mild, moderate, or severe disease activity. US and MRI performed within a 4-month period of surgery were scored for disease activity. The correlation between histology and imaging scores was examined.Results.Four of 14 patients were receiving anti-tumor necrosis factor (TNF) therapy, 4 were receiving methotrexate (MTX) alone, 4 were taking MTX and hydroxychloroquine (HCQ), and 1 was taking HCQ and sulfasalazine. Four specimens had severe, 6 moderate, 3 mild, and 2 minimal disease activity on histology. Three of 4 specimens with minimal and mild histology were observed in subjects receiving anti-TNF therapy. Synovitis was noted on greyscale in 80% of joints and Doppler signal in 60%. MRI demonstrated synovitis and bone marrow edema in 86% of images. Positive but not significant correlations were noted between histology and synovitis scores on US.Conclusion.Despite clinical remission, histology and imaging studies documented a persistently active disease state that may explain the mechanism for radiographic progression.

scholarly journals Peripheral Blood Gene Expression and IgG Glycosylation Profiles as Markers of Tocilizumab Treatment in Rheumatoid Arthritis

2012 ◽  
Vol 39 (5) ◽  
pp. 916-928 ◽  
Author(s):  
BERTALAN MESKO ◽  
SZILARD POLISKA ◽  
SZILVIA SZAMOSI ◽  
ZOLTAN SZEKANECZ ◽  
JANOS PODANI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Peripheral Blood ◽  
Multiple Testing ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Response To Treatment ◽  
Peripheral Blood Mononuclear ◽  
Gene Sets

Objective.Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has recently been approved as a biological therapy for rheumatoid arthritis (RA) and other diseases. It is not known if there are characteristic changes in gene expression and immunoglobulin G glycosylation during therapy or in response to treatment.Methods.Global gene expression profiles from peripheral blood mononuclear cells of 13 patients with RA and active disease at Week 0 (baseline) and Week 4 following treatment were obtained together with clinical measures, serum cytokine levels using ELISA, and the degree of galactosylation of the IgG N-glycan chains. Gene sets separating responders and nonresponders were tested using canonical variates analysis. This approach also revealed important gene groups and pathways that differentiate responders from nonresponders.Results.Fifty-nine genes showed significant differences between baseline and Week 4 and thus correlated with treatment. Significantly, 4 genes determined responders after correction for multiple testing. Ten of the 12 genes with the most significant changes were validated using real-time quantitative polymerase chain reaction. An increase in the terminal galactose content of N-linked glycans of IgG was observed in responders versus nonresponders, as well as in treated samples versus samples obtained at baseline.Conclusion.As a preliminary report, gene expression changes as a result of tocilizumab therapy in RA were examined, and gene sets discriminating between responders and nonresponders were found and validated. A significant increase in the degree of galactosylation of IgG N-glycans in patients with RA treated with tocilizumab was documented.

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