Serum Tumor Necrosis Factor-Alpha as a Competent Biomarker for Evaluation of Disease Activity in Early Rheumatoid Arthritis

Illahi, Mehreen Inam Illahi Inam; Amjad, Sofia; Alam, Syed Mehfooz; Ahmed, Syed Tousif; Fatima, Murk; Shahid, Muhammad Furqan

doi:10.7759/cureus.15314

Cited by 17 publications

(17 citation statements)

References 27 publications

(40 reference statements)

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“…Studies have shown increased serum level of BAFF/BLyS in RA patients (compared to healthy patients) despite long term intake of anti-inflammatory medications [ 27 ]. It seems that the TNF-α biomarker family may contribute to greater disease activity [ 21 , 28 ]. The results of this study are in agreement with previous clinical and experimental studies showing increased expression of lymphocyte B stimulatory cytokines (BAFF/BLyS) in sites with inflammatory periodontal and peri-implant bone destruction [ 21 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Biomarkers in Peri-Implant Health and Disease: A Cross-Sectional Pilot Study

Chaparro

Beltrán

Betancur

et al. 2022

IJMS

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Background: The aim of this feasibility study was to investigate the concentration level of CCL-20/MIP-3α, BAFF/BLyS, IL-23, RANKL, and Osteoprotegerin in the Peri-Implant Crevicular Fluid (PICF), from patients diagnosed with peri-implant mucositis and peri-implantitis, and to compare them with PICF from patients with healthy implants. Methods: Participants with at least one dental implant with healthy peri-implant tissues, peri-implant mucositis, or peri-implantitis were included. PICF was collected using paper strips from healthy and diseased peri-implant sites (n = 19). Biomarker levels were analyzed using a custom Multiplex ELISA Assay Kit. Results: In comparison to peri-implant health, the peri-implant mucositis group showed an increased concentration of CCL-20 MIP-3α, BAFF/BLyS, IL-23, RANKL, and Osteoprotegerin. The peri-implantitis group had the lowest median concentration of Osteoprotegerin (1963 ng/mL); this group had a similar concentration of RANKL (640.84 ng/mL) when compared to the peri-implant health group. BAFF/BLyS (17.06 ng/mL) showed the highest concentration in the peri-implantitis group. Conclusions: This feasibility study suggests that IL-23 and RANKL may help to elucidate the pathogenesis during the conversion from peri-implant health to peri-implantitis. Further research is required in BAFF/BLyS for the early diagnosis of peri-implantitis.

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Section: Discussionmentioning

confidence: 99%

Molecular Biomarkers in Peri-Implant Health and Disease: A Cross-Sectional Pilot Study

Chaparro

Beltrán

Betancur

et al. 2022

IJMS

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“…Furthermore, our in vitro experiments showed that the proinflammatory cytokine TNF‐α plays a key role in the PAD‐mediated citrullination of proteins in cardiomyocytes. These novel findings suggest that TNF‐α is not only a valuable predictive biomarker of disease activity in RA patients, 48 , 49 , 50 but it is also involved in modulating excitation‐contraction coupling in cardiomyocytes through PAD‐dependent signaling.…”

Section: Discussionmentioning

confidence: 91%

Citrullination is linked to reduced Ca²⁺ sensitivity in hearts of a murine model of rheumatoid arthritis

et al. 2022

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Aims Cardiac contractile dysfunction is prevalent in rheumatoid arthritis (RA), with an increased risk for heart failure. A hallmark of RA has increased levels of peptidyl arginine deaminases (PAD) that convert arginine to citrulline leading to ubiquitous citrullination, including in the heart. We aimed to investigate whether PAD‐dependent citrullination in the heart was linked to contractile function in a mouse model of RA during the acute inflammatory phase. Methods We used hearts from the collagen‐induced arthritis (CIA) mice, with overt arthritis, and control mice to analyze cardiomyocyte Ca2+ handling and fractional shortening, the force‐Ca2+ relationship in isolated myofibrils, the levels of PAD, protein post‐translational modifications, and Ca2+ handling protein. Then, we used an in vitro model to investigate the role of TNF‐α in the PAD‐mediated citrullination of proteins in cardiomyocytes. Results Cardiomyocytes from CIA mice displayed larger Ca2+ transients than controls, whereas cell shortening was similar in the two groups. Myofibrils from CIA hearts required higher [Ca2+] to reach 50% of maximum shortening, ie Ca2+ sensitivity was lower. This was associated with increased PAD2 expression and α‐actin citrullination. TNF‐α increased PAD‐mediated citrullination which was blocked by pre‐treatment with the PAD inhibitor 2‐chloroacetamide. Conclusion Using a mouse RA model we found evidence of impaired cardiac contractile function linked to reduced Ca2+ sensitivity, increased expression of PAD2, and citrullination of α‐actin, which was triggered by TNF‐α. This provides molecular and physiological evidence for acquired cardiomyopathy and a potential mechanism for RA‐associated heart failure.

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“…Some studies suggested that the release of metalloproteinase and pro-inflammatory cytokines can be considered among the causes of RA which are related to environmental factors such as smoking, genetic (via epigenetics), microbiome culture, and also presence of periodontitis and can cause the destruction of cartilage and bone finally [28]. Some studies have shown that an increase in proinflammatory cytokines is directly related to the disease activity score in RA [8,29].…”

Section: Discussionmentioning

confidence: 99%

Effects of Melatonin on Sleep Quality and Disease Activity in Patients With Rheumatoid Arthritis

et al. 2022

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Background and Objective In rheumatoid arthritis (RA) patients sleep disturbance is one of serious and prevalent problems. Considering the known effects of melatonin on sleep quality and inflammation, this study aimed to investigate melatonin supplementation effect on quality of sleep and disease activity in patients with RA.Methods In this randomized, placebo-controlled trial (double-blind), 64 RA patients were selected and divided into experimental and placebo groups randomly; experimental group received 3 mg/d of melatonin and another group consumed placebo for 60 days. Before and after the investigation, assessment of the quality of sleep determined using the Pittsburgh Sleep Quality Index (PSQI). Disease Activity Score-28 (DAS28) and the Visual Analogue Scale (VAS) questionnaires were used for evaluation of disease activity and pain intensity, respectively.Results Melatonin significantly reduced PSQI, DAS28 and VAS scores, when values compared with baseline. In contrast to placebo group, good sleep quality within the melatonin group increased significantly compared to baseline and this improvement in sleep quality was significant when compared between groups. The scores of DAS28 and pain VAS at the end of trial were significantly reduced compared to the baseline in both groups. However, reduction in the DAS28 and VAS scores of the melatonin group were stronger than reductions in the placebo receiving group.Conclusions This study results revealed that melatonin was safe and effective in improving sleep quality and reducing DAS28 and pain VAS scores in RA patients.

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Serum Tumor Necrosis Factor-Alpha as a Competent Biomarker for Evaluation of Disease Activity in Early Rheumatoid Arthritis

Abstract: Inam illahi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cited by 17 publications

References 27 publications

Molecular Biomarkers in Peri-Implant Health and Disease: A Cross-Sectional Pilot Study

Molecular Biomarkers in Peri-Implant Health and Disease: A Cross-Sectional Pilot Study

Citrullination is linked to reduced Ca²⁺ sensitivity in hearts of a murine model of rheumatoid arthritis

Effects of Melatonin on Sleep Quality and Disease Activity in Patients With Rheumatoid Arthritis

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Serum Tumor Necrosis Factor-Alpha as a Competent Biomarker for Evaluation of Disease Activity in Early Rheumatoid Arthritis

Abstract: Inam illahi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cited by 17 publications

References 27 publications

Molecular Biomarkers in Peri-Implant Health and Disease: A Cross-Sectional Pilot Study

Molecular Biomarkers in Peri-Implant Health and Disease: A Cross-Sectional Pilot Study

Citrullination is linked to reduced Ca2+ sensitivity in hearts of a murine model of rheumatoid arthritis

Effects of Melatonin on Sleep Quality and Disease Activity in Patients With Rheumatoid Arthritis

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Citrullination is linked to reduced Ca²⁺ sensitivity in hearts of a murine model of rheumatoid arthritis