scholarly journals Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260254
Author(s):  
Haruki Matsumoto ◽  
Yuya Fujita ◽  
Tomoyuki Asano ◽  
Naoki Matsuoka ◽  
Jumpei Temmoku ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cytokines ◽  
Immune Checkpoint ◽  
Elevated Serum ◽  
Joint Damage ◽  
Serum Levels ◽  
Immune Checkpoint Molecules ◽  
Tnf Α ◽  
Checkpoint Molecule ◽  
Acpa Status

Background Anti-citrullinated peptide antibodies (ACPA) and inflammatory cytokines play important roles in the development of rheumatoid arthritis (RA). T cell immunoglobulin and mucin–domain containing–3 (TIM–3) is an immune-checkpoint molecule involved in inhibitory signaling. Galectin–9 (Gal–9) mediated ligation of TIM–3 induces the amelioration of autoimmune diseases. TIM–3 is expressed in synovial osteoclasts and involved in the rheumatoid bone destruction. The aim of this study was to investigate the relationships between inflammatory cytokines and immune–checkpoint molecules in RA patients. Methods Serum levels of interleukin–6 (IL–6), tumor necrosis factor–α (TNF–α), soluble TIM–3 (sTIM–3) and Gal–9 were determined by ELISA. Patients were stratified into two groups based on ACPA titers: low-medium ACPA (ACPA <200 U/mL) and high ACPA (ACPA ≥200 U/mL). Serum levels of cytokines or immune-checkpoint molecules were evaluated between RA patients with low-medium ACPA titers and high ACPA titers. Results Elevated serum levels of inflammatory cytokines were correlated with DAS28–ESR in RA patients. Although serum levels of sTIM–3 were elevated in RA patients, significant correlations between sTIM–3 and cytokines (IL–6 or TNF–α) were observed exclusively in RA patients with low-medium ACPA titers (<200 U/mL). Serum levels of IL–6 and TNF–α levels were significantly correlated with elevated Gal–9 levels regardless of ACPA status. A significant correlation between IL–6 and Gal–9 was observed in RA patients without advanced joint damage. Conversely, a significant correlation between TNF–α and Gal–9 was observed in RA patients with advanced joint damage. Conclusions Our data indicated that there are positive correlations between circulating inflammatory cytokines and checkpoint molecules in RA patients and these interactions can be modulated by ACPA status or joint damage stage.

scholarly journals Association Between Inflammatory Cytokines and Immune-Checkpoint Molecule in Rheumatoid Arthritis

2021 ◽  
Author(s):  
Haruki Matsumoto ◽  
Yuya Fujita ◽  
Tomoyuki Asano ◽  
Naoki Matsuoka ◽  
Jumpei Temmoku ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Immune Checkpoint ◽  
Joint Damage ◽  
Japanese Patients ◽  
Serum Levels ◽  
Stage I ◽  
Stage Ii ◽  
Positive Correlation ◽  
Tnf Α ◽  
Acpa Status

Abstract BackgroundRheumatoid arthritis (RA) is a heterogeneous inflammatory disease. Both anti-citrullinated peptide antibodies (ACPA) and inflammatory cytokines play an important role in the development of RA. The aim of this study was to investigate the association between inflammatory cytokines and co-inhibitory checkpoint molecules in patients with RA.MethodsOne hundred and thirty-two Japanese patients with established RA were enrolled. Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α) were determined by ELISA. Patients were stratified into two groups based on ACPA titers: low-medium ACPA (ACPA <200 U/mL) and high ACPA (ACPA ≥200 U/mL). Serum levels of cytokines or co-inhibitory checkpoint molecules were compared according to the status of ACPA titers and joint progression stage.ResultsBaseline serum levels of TNF-α and IL-6 were significantly elevated in RA patients; however, the two cytokines showed no correlation with each other. Serum levels of IL-6 or TNF-α showed a significant correlation with DAS28-CRP, independent of ACPA status. Although serum levels of soluble T-cell immunoglobulin and mucin-domain containing-3 (sTIM-3) were elevated in RA patients, significant correlation of sTIM-3 with IL-6 or TNF-α was only observed in RA patients with low-medium levels of ACPA titers (<200 U/mL). Serum levels of IL-6 and TNF-α were significantly correlated with elevated levels of galectin-9 (Gal-9) independent of ACPA status. Whereas, a significant correlation between IL-6 and Gal-9 was observed only in RA patients without advanced joint damage (Stage I). Conversely, significant correlation between TNF-α and Gal-9 was observed only in RA patients with advanced joint damage (Stage II–IV).ConclusionsRA patients may be differentiated based on the interplay between serum cytokines and co-inhibitory molecules. RA patients with minimal joint damage (Stage I) appear to show positive correlation between Gal-9 and IL-6. Conversely, RA patients with advanced joint damage (Stage II–IV) appear to show positive correlation between Gal-9 and TNF-α. Serum levels of cytokines and immune-checkpoint molecules may be useful markers for predicting the immune phenotype and further personalized treatment of RA.

Genetic Variation in TNF-α, its Relation with Inflammatory Biomarkers and Susceptibility to Rheumatoid Arthritis

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Khadiga Ahmed Ismail
Keyword(s):  
Rheumatoid Arthritis ◽  
Serum Level ◽  
Functional Disability ◽  
Serum Levels ◽  
Amplification Refractory Mutation System ◽  
Reactive Protein ◽  
Tnf Α ◽  
Mutation System ◽  
Potential Factor ◽  
Factor Α

Background: Tumor necrosis Factor-α (TNF-α) is encoded and controlled by TNF-α gene, which is involved in rheumatoid arthritis (RA) susceptibility. This research aimed to identify genetic variations of TNF-α (G308A) and to establish its association with inflammatory markers in Rheumatoid Arthritis predisposition. Methods: In the present study, fifty RA patients and fifty volunteers were involved and evaluated for the C-reactive protein, rheumatoid factor, and TNF-α were estimated by ELISA, Erythrocyte Sedimentation Rate (ESR) by Wintergreen method and for TNF-α-308 G>A polymorphism by polymerase chain reaction with amplification refractory mutation system (PCR-ARMS). Results: The CRP, RF, ESR and TNF-α were significantly elevated in RA patients relative to controls. The serum level TNF-α was also significantly elevated in female patients and in patients ≥50 years. Analysis of TNF-308 gene polymorphism revealed that GG genotypes were more prevalent in RA patients than in the healthy individuals and that GG genotype may be a potential factor to RA. The G allele was more common in RA than in the control. Elevated TNF-α serum levels were significantly associated the GG genotype and functional disability in RA patients. Conclusion: TNF-α promoter 308polymorphism GG genotype may be considered as a risk factor for RA and the TNF-α serum level was significantly related to the functional disability in the disease.

Evaluating the efficacy of intra-articular injections of platelet rich plasma (PRP) in rheumatoid arthritis patients and its impact on inflammatory cytokines, disease activity and quality of life.

2020 ◽  
Vol 16 ◽  
Author(s):  
Dalia S. Saif ◽  
Nagwa N. Hegazy ◽  
Enas S. Zahran
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Cytokines ◽  
Platelet Rich Plasma ◽  
Joint Inflammation ◽  
Monthly Interval ◽  
Post Injection ◽  
Tnf Α

Background: Among rheumatoid arthritis patients (RA), general disease activity is well regulated by diseasemodifying anti-rheumatic medications (DMARDS), but sometimes local inflammation still persists among a few joints. Adjuvant modern molecular interventions as Platelet Rich Plasma (PRP) with a suggested down regulating effect on inflammatory mediators has a proven effect in management of RA. We aim to evaluate the therapeutic effect of intra-articular PRP versus steroid in RA patients and their impact on inflammatory cytokines IL1B , TNF α, local joint inflammation, disease activity and quality of life (QL). Methods: Open labeled parallel randomized control clinical trial was carried out on 60 RA patients randomly divided into 2 groups, Group 1: included 30 patients received 3 intra-articular injections of PRP at monthly interval, Group 2: included 30 patients received single intra-articular injection of steroid. They were subjected to clinical, laboratory, serum IL1B and TNF α assessment at baseline and at 3, 6 months post injection. Results: Patients of both groups showed improvements in their scores of evaluating tools at 3months post injection and this improvement was persistent in the PRP group up to 6 months post injection while it was continued only for 3 months in the steroid group. Conclusions: PRP is a safe, effective and useful therapy in treating RA patients who had insufficient response and persistent pain and inflammation in just one or two joints through its down regulating effect on inflammatory cytokines IL1B, TNF α with subsequent improvement of local joint inflammation, disease activity and QL.

Increased Serum Interleukin 22 in Patients with Rheumatoid Arthritis and Correlation with Disease Activity

2012 ◽  
Vol 39 (7) ◽  
pp. 1320-1325 ◽  
Author(s):  
LAURINDO FERREIRA da ROCHA ◽  
ÂNGELA LUZIA BRANCO PINTO DUARTE ◽  
ANDRÉA TAVARES DANTAS ◽  
HENRIQUE ATAÍDE MARIZ ◽  
IVAN da ROCHA PITTA ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Mononuclear Cells ◽  
Activity Index ◽  
Elevated Serum ◽  
Serum Levels ◽  
Peripheral Blood Mononuclear ◽  
Additional Tool ◽  
Bone Erosions ◽  
Interleukin 22

Objective.To analyze the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA).Methods.IL-22 serum levels were measured in 83 patients with established RA under treatment with disease-modifying antirheumatic drugs and in 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of IL-22 serum levels with disease activity measures [Clinical Disease Activity Index (CDAI) and Disease Activity Score for 28 joints (DAS28)], serological markers, bone erosions, and demographic factors were assessed. Peripheral blood mononuclear cells (PBMC) from 30 patients with RA and 14 controls were purified and stimulatedin vitrowith phorbol myristate acetate (PMA)/ionomycin. IL-22 production by PBMC and in serum was investigated by ELISA.Results.IL-22 levels were increased in patients with RA compared with controls (mean 432.37 pg/ml and 67.45 pg/ml, respectively; p < 0.001). Levels of IL-22 correlated with DAS28 and CDAI measures. Rheumatoid factor (RF) positivity was correlated with higher levels of IL-22 in patients with RA (mean 575.08 pg/ml; p = 0.001). The presence of bone erosions was associated with high IL-22 levels (p = 0.0001). PBMC stimulated with PMA/ionomycin expressed higher levels of IL-22 in patients with RA than controls but this was not significant (mean 584.75 pg/ml and 295.57 pg/ml; p = 0.553).Conclusion.IL-22 is elevated in the serum of patients with established RA. Elevated serum IL-22 allows discrimination between patients with different clinical and laboratory measures and indicates the potential of IL-22 as an additional tool for assessment of activity in RA, particularly in patients with RF antibodies and longterm disease. IL-22 is associated with bone-destructive disease.

OP0049 A Genetic Variant in the Region of MMP-9 is Associated with Serum Levels and Progression of Joint Damage in Rheumatoid Arthritis

2013 ◽  
Vol 72 (Suppl 3) ◽  
pp. A66.2-A66 ◽  
Author(s):  
D. De Rooy ◽  
A. Zhernakova ◽  
R. Tsonaka ◽  
A. Willemze ◽  
F. Kurreeman ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Genetic Variant ◽  
Joint Damage ◽  
Serum Levels

scholarly journals Are Leptin and Cytokines Involved in Body Weight Gain during Treatment with Antipsychotic Drugs?

2002 ◽  
Vol 47 (8) ◽  
pp. 742-749 ◽  
Author(s):  
Trino Baptista ◽  
Serge Beaulieu
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Antipsychotic Drugs ◽  
Causal Relation ◽  
Body Weight Gain ◽  
Serum Insulin ◽  
Elevated Serum ◽  
Serum Levels ◽  
Metabolism Regulation ◽  
Tnf Α

Objective: To critically review published literature on the causal association between leptin, cytokines, and excessive body weight gain (BWG) induced by antipsychotic drugs (APs). Methods: We completed a Medline search using the words leptin, cytokines, antipsychotic drugs, neuroleptics, psychotropic drugs, weight gain, and obesity. We also included our empirical research on this topic in the discussion. We examined the relation between leptin, cytokines (mainly tumour necrosis factor alpha [TNF-α] and its soluble receptors), and AP-induced BWG, using the biological sciences' current theories of causality. Results: In the general field of weight regulation, there is scarce experimental evidence that leptin or TNF-α by themselves can induce obesity. Serum levels of leptin and TNF-α rather increase simultaneously as BWG occurs. This has also been reported during AP-induced BWG, with the equivocal exception of a study with clozapine. Some researchers have suggested that the absence of the expected correlation between leptin and body mass index (BMI) or serum insulin levels, and the lack of sex-related differences in leptin levels in AP-treated patients, may point to a causal relation. This contention requires more experimental support. In addition, future clinical studies must carefully control for sex and BMI. Conclusions: No conclusive evidence has been provided that leptin or TNF-α may induce obesity either in drug-free subjects or in AP-treated patients. In most cases, the elevated serum levels of these hormones appear to be a consequence rather than a cause of obesity. That does not mean that such an elevation is innocuous, since it may impair blood pressure and also carbohydrate and lipid metabolism regulation. Hence, all efforts should be made to prevent or attenuate BWG during treatment with APs.

scholarly journals Elevated Serum Levels of Resistin, Leptin, and Adiponectin are Associated with C-reactive Protein and also Other Clinical Conditions in Rheumatoid Arthritis

2011 ◽  
Vol 50 (4) ◽  
pp. 269-275 ◽  
Author(s):  
Takumi Yoshino ◽  
Natsuko Kusunoki ◽  
Nahoko Tanaka ◽  
Kaichi Kaneko ◽  
Yoshie Kusunoki ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Elevated Serum ◽  
Serum Levels ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Clinical Conditions

Interleukin-6, Hepcidin, and Other Biomarkers in Anemia of Chronic Disease (ACD) and Chemotherapy-Induced Anemia (CIA): Potential Therapeutic Targets.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2086-2086 ◽  
Author(s):  
Saroj Vadhan-Raj ◽  
Xiao Zhou ◽  
Carlos E. Bueso-Ramos ◽  
Shreyaskumar Patel ◽  
Robert S Benjamin ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Inflammatory Cytokines ◽  
Linear Regression Analysis ◽  
Transferrin Saturation ◽  
Serum Levels ◽  
Serum Samples ◽  
Anemia Of Chronic Disease ◽  
Baseline Serum ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract Abstract 2086 Background: Anemia in patients with malignancies can be multifactorial including anemia of chronic disease (ACD), also known as anemia of inflammation (AI), and chemotherapy (CT)-induced anemia (CIA) from myelosuppression. Although, exact mechanism for ACD is not known, induction of hepcidin, a key iron-regulatory hormone, by Interleukin (IL)-6 and other pro-inflammatory cytokines with resulting hypoferremia and limitation of iron supply to the bone marrow appear to be major contributors to pathogenesis of anemia. Hepcidin reduces iron levels by inducing degradation of the cellular iron exporter, ferroportin. The objective of this study was to examine the levels of various cytokines/regulators that may play role in ACD. Methods: Chemo-naïve patients with sarcoma scheduled to initiate first-line doxorubicin-based chemotherapy had blood samples drawn at baseline, and following chemotherapy (post cycles1, 3 and 6) for analysis of pro-inflammatory cytokines/other biomarkers of anemia. Serum samples were analyzed for IL-1β, IL-6, TNF-α, Hepcidin, hemojuvelin, ferroportin, soluble transferrin receptor (sTFR), and C-reactive protein (CRP) using ELISA techniques (R&D Diagnostics, Uscn Life Science Inc, or Abnova). Correlations between these biomarkers and Hgb levels at baseline and during the study period were calculated by linear regression analysis (SAS 9.2). Results: Of the 49 patients enrolled on to the clinical trial, there were 26 (53%) women and 23 (47%) men, with median age 45 years (range 19–65 years). Twenty-five percent of the patients had Hgb less than 12g/dL (range, 8.9–15.9 g/dL) prior to CT. At baseline, 50% of the pts had hypoferremia with low serum iron and transferrin saturation <20%. Baseline serum levels of IL-6 (r= −0.73, p<0.0001), hepcidin (r= −0.46, p=0.005), CRP (r= −0.46, p=0.003), sTFR (r= −0.32, p=0.064) inversely correlated with hemoglobin levels prior to CT, supporting their role in ACD. During CT (median 4, range; 1–6 cycles), Hgb declined in all pts with 55% requiring PRBC transfusions (77% of pts starting with baseline Hgb < 12 g/dL vs 47% of pts with baseline Hgb > 12 g/dL). Interestingly, as shown below, Hepcidin, IL-6, and sTFR all significantly negatively correlated with Hgb levels during CT. No significant correlation was found for IL-1β, TNF-α, ferroportin, or hemojuvelin levels with Hgb. Conclusions: IL-6 and Hepcidin pathway appears to play an important role in anemia in cancer patients before and during CT. Treatment with novel agents targeting this pathway may provide effective strategies for prevention and treatment of ACD and CIA. Disclosures: Vadhan-Raj: JNJ: Research Funding.

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