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

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Khadiga Ahmed Ismail

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.

2020 ◽  
Vol 14 (4) ◽  
pp. 2453-2465
Author(s):  
Ramadan Yahia ◽  
Shereen M. Mohammed ◽  
Manal M. Hassanien ◽  
Shabaan H. Ahmed ◽  
Helal F. Hetta

Rheumatoid arthritis (RA) is a systemic inflammatory disease with chronic nature of joints related to autoimmunity. Vitamin D was found to modulate cell growth, function of immune cells and anti-inflammatory action. The aims of that study were to investigate serum level of vitamin D and some cytokines and to identify the correlation between vitamin D and these cytokines in RA. Totally 40 RA patients without vitamin D supplement were involved in this study. Serum level of vitamin D, interleukin-6 (IL-6), IL-10, IL-35, C-reactive protein (CRP) and tumor necrosis factor α (TNF-α), all of them were measure in all patients by enzyme-linked immunosorbent assay (ELISA). Patients were classified according to Vitamin D levels into two groups; RA patients with Vit. D deficiency (n=25) and RA patients with Vit. D sufficiency (n=15). IL-6 was lower significantly (P = 0.03) in RA patients with Vit. D sufficiency than RA patients with Vit. D deficiency. IL-10 and IL-35 were higher significantly (P = 0.0234, P = 0.0356 respectively) in RA patients with Vit. D sufficiency than RA patients with Vit. D deficiency. Vit. D was significantly positively correlated with both IL-10 (r = 0.4516, P = 0.0034) and IL-35 (r = 0.3424, P = 0.0329) and negatively correlated with IL-6 (r = -0.3188, P = 0.0479). Sufficient serum level of Vit. D is correlated with higher level of anti-inflammatory cytokines (IL-10 and IL-35) and lower level of IL-6. This support the immunomodulatory effect of Vit. D in RA.


2011 ◽  
Vol 38 (5) ◽  
pp. 821-827 ◽  
Author(s):  
SHI-YAO WANG ◽  
YAN-YING LIU ◽  
HUA YE ◽  
JIAN-PING GUO ◽  
RU LI ◽  
...  

Objective.To explore the potential role of Dickkopf-1 (DKK-1) in rheumatoid arthritis (RA) and to evaluate the effect of a tumor necrosis factor-α (TNF-α) inhibitor (infliximab) and an interleukin 1 receptor antagonist (IL-1Ra; anakinra) on DKK-1 secretion in patients with RA.Methods.Serum samples were collected from 100 patients with RA, 100 patients with other rheumatic diseases (e.g., osteoarthritis and ankylosing spondylitis), and 40 healthy controls. DKK-1 and osteoprotegerin (OPG) levels in serum were detected by ELISA. Serum C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), rheumatoid factor (RF) titers, and anti-cyclic citrullinated peptide antibody were also measured in patients with RA.Results.The serum level of DKK-1 was significantly higher in patients with RA than in healthy controls and those with other rheumatic diseases (p < 0.01); the serum DKK-1 level was correlated with levels of CRP (r = 0.488, p = 0.003) and ESR (r = 0.458, p = 2.4 x 10−4) and the Sharp score of radiologic change (r = 0.449, p = 0.001) in RA. In contrast to the increasing level of OPG, DKK-1 was significantly decreased in RA patients treated with TNF-α inhibitor (p < 0.01). DKK-1 was significantly decreased in RA patients treated with IL-1Ra (p < 0.01).Conclusion.DKK-1, as an important mediator, was correlated with bone erosion and inflammation in RA. The change of DKK-1 level may serve as a biomarker of disease activity and bone erosion.


2020 ◽  
Author(s):  
Jiaojiao Wang ◽  
Chuanxin Wu ◽  
Yunying Wang ◽  
Chongxiang Chen ◽  
Jing Cheng ◽  
...  

AbstractBackgroundHigh mobility group box 1 (HMGB1) is an important “late” inflammatory mediator in bacterial sepsis. Ethyl pyruvate (EP), an inhibitor of HMGB1, can prevent bacterial sepsis by decreasing HMGB1 levels. However, the role of HMGB1 in fungal sepsis is still unclear. Therefore, we investigated the role of HMGB1 and EP in invasive C. albicans infection.MethodsWe measured serum HMGB1 levels in patients with sepsis with C. albicans infection and without fungal infection, and control subjects. We collected clinical indices to estimate correlations between HMGB1 levels and disease severity. Furthermore, we experimentally stimulated mice with C. albicans and C. albicans + EP. Then, we examined HMGB1 levels from serum and tissue, investigated serum levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), determined pathological changes in tissues, and assessed mortality.ResultsSerum HMGB1 levels in patients with severe sepsis with C. albicans infection were elevated. Increased HMGB1 levels were correlated with procalcitonin (PCT), C-reactive protein (CRP), 1,3-β-D-Glucan (BDG) and C. albicans sepsis severity. HMGB1 levels in serum and tissues were significantly increased within seven days after mice were infected with C. albicans. The administration of EP inhibited HMGB1 levels, decreased tissue damage, increased survival rates and inhibited the release of TNF-α and IL-6.ConclusionsHMGB1 levels were significantly increased in invasive C. albicans infections. EP prevented C. albicans lethality by decreasing HMGB1 expression and release. HMGB1 may provide an effective diagnostic and therapeutic target for invasive C. albicans infections.


2020 ◽  
Vol 9 (5) ◽  
pp. 1377
Author(s):  
Anna Szeremeta ◽  
Agnieszka Jura-Półtorak ◽  
Aleksandra Zoń-Giebel ◽  
Magdalena Kopeć-Mędrek ◽  
Eugeniusz Józef Kucharz ◽  
...  

This study was performed to evaluate the effects of 15-month anti-tumor necrosis factor α (anti-TNF-α) therapy on the aggrecan turnover of female rheumatoid arthritis (RA) patients. Serum was obtained from healthy subjects and female RA patients treated with TNF-α inhibitors (TNFαI) in combination with methotrexate. We measured serum levels of aggrecan chondroitin sulfate 846 epitope (CS846), aggrecan fragments (AGC), disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and 5 (ADAMTS-5), as well as their natural inhibitor, known as tissue inhibitor of matrix metalloproteinase-3 (TIMP-3), using immunoassay methods. Serum levels of CS846, AGC, ADAMTS-4, ADAMTS-5 and TIMP-3 were higher in female patients with RA before the treatment in comparison to healthy subjects. Ratio of ADAMTS-5 to TIMP-3 was significantly higher in RA women than in controls, whereas ADAMTS-4/TIMP-3 ratio did not differ from that in controls. During the anti-TNF-α therapy, the serum levels of 846 epitope increased, whereas levels of AGC decreased in female RA patients. Furthermore, 15 months of treatment with TNFαI downregulated serum levels of both ADAMTS, without any effect on TIMP-3 levels. These changes were accompanied by significantly reduced ratios of ADAMTS to TIMP-3. According to our results, anti-TNF-α therapy has a beneficial impact on aggrecan remodeling during RA.


Author(s):  
Sisi Yan ◽  
Jinli Ding ◽  
Yi Zhang ◽  
Jiayu Wang ◽  
Sainan Zhang ◽  
...  

Abstract Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease. It has been reported that chronic low-grade inflammation might participate in its pathogenesis. C1q and TNF related 6 (C1QTNF6) is a newly identified adiponectin paralog associated with inflammation. The aim of the present study was to investigate the role of C1QTNF6 in the development of chronic inflammation in PCOS and the underlying molecular mechanism. After analyzing the expression of C1QTNF6 in the serum and granulosa cells (GCs) of PCOS patients and healthy controls, we verified the roles of C1QTNF6 in inflammation through dehydroepiandrosterone-induced PCOS mouse models and cell models of lipopolysaccharide (LPS)-induced inflammation. The results demonstrated that C1QTNF6 expression in the serum and GCs of patients with PCOS was significantly elevated compared with those of the controls, and similar results were observed in the serum and ovary of PCOS mouse models. In PCOS mice and C1QTNF6-overexpressing PCOS mice, serum levels of pro-inflammatory factors including C-reactive protein (CRP), interleukin 6 (IL6) and tumor necrosis factor-α (TNFα) were increased, while the opposite effects were observed when C1QTNF6 was downregulated in PCOS mice. Furthermore, C1QTNF6 overexpression upregulated the levels of TNFα, IL6, and CRP and activated the AKT/NF-κB pathway in LPS-treated KGN cells, whereas C1QTNF6 knockdown and BAY-117082 (an NF-κB inhibitor) treatment resulted in the opposite effects. Taken together, our results indicate that C1QTNF6 is involved in the pathogenesis of PCOS by affecting the inflammatory response via the AKT/NF-κB signaling pathway.


2021 ◽  
Vol 11 (4) ◽  
pp. 309
Author(s):  
Vincenzo Di Leo ◽  
Patrick J. Gleeson ◽  
Fabio Sallustio ◽  
Carine Bounaix ◽  
Jennifer Da Silva ◽  
...  

IgA Nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by the mesangial deposition of abnormally glycosylated IgA1 (Gd-IgA). The production of Gd-IgA occurs in mucose-associated lymphoid tissue (MALT). The microbiota plays a role in MALT modulation. Rifaximin (NORMIX®), a non-absorbable oral antibiotic, induces positive modulation of the gut microbiota, favoring the growth of bacteria beneficial to the host. Here, we evaluate the effect of rifaximin on a humanized mice model of IgAN (α1KI-CD89Tg). Methods: The α1KI-CD89Tg mice were treated by the vehicle (olive oil) or rifaximin (NORMIX®). Serum levels of hIgA, hIgA1–sCD89, and mIgG–hIgA1 immune complexes were determined. Glomerular hIgA1 deposit and CD11b+ cells recruitment were revealed using confocal microscopy. Furthermore, the mRNA of the B-Cell Activating Factor (BAFF), polymeric immunoglobulin receptor (pIgR), and Tumor Necrosing Factor-α (TNF-α) in gut samples were detected by qPCR. Results: Rifaximin treatment decreased the urinary protein-to-creatinine ratio, serum levels of hIgA1–sCD89 and mIgG–hIgA1 complexes, hIgA1 glomerular deposition, and CD11b+ cell infiltration. Moreover, rifaximin treatment decreased significantly BAFF, pIgR, and TNF-α mRNA expression. Conclusions: Rifaximin decreased the IgAN symptoms observed in α1KI-CD89Tg mice, suggesting a possible role for it in the treatment of the disease.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Joanna Salomon ◽  
Łukasz Matusiak ◽  
Danuta Nowicka-Suszko ◽  
Jacek C Szepietowski

Chitinase-3-like protein 1 (YKL-40) is suggested to be associated with type 2 T helper response and atopy. The aim of the study was the evaluation of serum YKL-40 level in atopic dermatitis. The study was performed on 59 patients: 27 males and 32 females, aged from 18 to 64 years. The severity of the disease was assessed by the SCORAD and objective SCORAD indexes. The severity of pruritus was measured by the visual analogue scale. Blood samples were taken to examine serum level of YKL-40, total IgE level, C-reactive protein level, white blood cell count, and neutrophil count. YKL-40 serum levels were significantly higher in patients with atopic dermatitis compared to the controls. There was a positive correlation between YKL-40 concentration and SCORAD, objective SCORAD, and pruritus. This study has shown that YKL-40 serum level is increased in patients with atopic dermatitis and reflects the severity of symptoms.


Bionatura ◽  
2021 ◽  
Vol 6 (4) ◽  
pp. 2228-2232
Author(s):  
Wedad Mahmood Lahmood Al-obaidi ◽  
Mohanad Hasan Mahmood Al-Izzi ◽  
Aya Saad yaseen

Carrot juice is a critical source of vitamins, selenium, and β-carotene, which is suggested to protect from Rheumatoid Arthritis (RA). The present study aimed to show the effect of carrot juice supplementation compared to selenium tablet supplementation, so our study includes (44) blood samples belonging to young men with RA. All patients aged (20-45) years, 44 blood samples were obtained before treatment at week (0), twenty-four men with RA were supplied with fresh carrot juice. The other group of 20 patients was given an artificial selenium supplement for 21 days as well, and the results were analyzed.The samples were collected from Kirkuk hospital, and external specialized clinical from October/2019 to September /2020; experimental groups were divided into three groups: Group 1 : (44) men Rheumatoid arthritis (RA) before treatment, Group 2: (24) men with RA+ Carrot juice, Group 3: (20) men with RA +Selenium Tab, We reach to following results: the patients who have RA consumption Carrot juice and patients take up Se tab. show significant decrease respectively in RBCs, WBCs, ERS, and RF compared with the Rheumatoid arthritis group, so as the results show a significant decrease in Leptin, IL-6, C-Reactive Protein, and TNF-α concentrations in comparison with the Rheumatoid arthritis group. In contrast, we found a significant increase in GSH, Selenium concentrations, and VD3 in men with RA administration carrot juice and patients' consumption Se tab. Respectively compared with the RA group and, finally, our finding shows no difference in Ceruloplasmin in experimental groups.


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