Direct recognition of LPS drive TLR4 expressing CD8+ T cell activation in patients with rheumatoid arthritis

Tripathy, Arun Kumar; Khanna, S. N.; Padhan, Prasanta; Smita, Shuchi; Raghav, Sunil K.; Gupta, Bhawna

doi:10.1038/s41598-017-01033-7

Cited by 44 publications

(29 citation statements)

References 50 publications

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“…In RA patients, CD4+ T-cell activation with subsequent differentiation into Th1 and Th17 has been suggested to be responsible for RA progression [156]. Furthermore, expression of TLR4 on CD8+ T cells was correlated woth RA severity [157]. Interestingly, a seven day fasting regimen resulted in a decrease in CD4+ and CD8+ lymphocyte levels and an increase in IL-4, which is known to have anti-inflammatory effects [158,159].…”

Section: Fasting Paradigmsmentioning

confidence: 99%

Human Postprandial Nutrient Metabolism and Low-Grade Inflammation: A Narrative Review

et al. 2019

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The importance of the postprandial state has been acknowledged, since hyperglycemia and hyperlipidemia are linked with several chronic systemic low-grade inflammation conditions. Humans spend more than 16 h per day in the postprandial state and the postprandial state is acknowledged as a complex interplay between nutrients, hormones and diet-derived metabolites. The purpose of this review is to provide insight into the physiology of the postprandial inflammatory response, the role of different nutrients, the pro-inflammatory effects of metabolic endotoxemia and the anti-inflammatory effects of bile acids. Moreover, we discuss nutritional strategies that may be linked to the described pathways to modulate the inflammatory component of the postprandial response.

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Section: Fasting Paradigmsmentioning

confidence: 99%

Human Postprandial Nutrient Metabolism and Low-Grade Inflammation: A Narrative Review

et al. 2019

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“…Fraser et al ( 74 ) observed that subtotal fasting where patients were allowed to have limited amount of vitamin and mineral supplementation, carbohydrate, and energy in form of vegetable juice decreased CD4 + lymphocyte activation and numbers. Activation of CD4 + T cell and further differentiation to Th1 and Th17 lineages are shown to be responsible for progression of RA ( 75 ). Thus, decreased T cell activation owing to 7–10 day fasting suggests a transient immunosuppression, thereby suppressing RA ( 74 ).…”

Section: Seven Days Fasting Followed By Vegan Dietmentioning

confidence: 99%

Managing Rheumatoid Arthritis with Dietary Interventions

2017

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Self-help by means of dietary interventions can help in management of various disorders including rheumatoid arthritis (RA), a debilitating autoimmune disease. Dietary interventions necessitate a widespread appeal for both patients as well as clinicians due to factors including affordability, accessibility, and presence of scientific evidences that demonstrate substantial benefits in reducing disease symptoms such as pain, joint stiffness, swelling, tenderness and associated disability with disease progression. However, there is still an uncertainty among the community about the therapeutic benefits of dietary manipulations for RA. In the present review, we provide an account of different diets and their possible molecular mechanism of actions inducing observed therapeutic benefits for remission and management of RA. We further indicate food that can be a potential aggravating factor for the disease or may help in symptomatic relief. We thereafter summarize and thereby discuss various diets and food which help in reducing levels of inflammatory cytokines in RA patients that may play an effective role in management of RA following proper patient awareness. We thus would like to promote diet management as a tool that can both supplement and complement present treatment strategies for a better patient health and recovery.

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“…These molecules are upregulated in some patients with RA and are expressed in the synovium 14. Numerous preclinical mechanistic studies have shown the potential role for TLR4 and its ligands in RA 15–24…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of NI-0101, an anti-toll-like receptor 4 monoclonal antibody, in patients with rheumatoid arthritis after inadequate response to methotrexate: a phase II study

Monnet¹,

Choy

McInnes

et al. 2019

Ann Rheum Dis

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ObjectivesAnti-citrullinated protein antibodies (ACPAs) form immune complexes with citrullinated proteins binding toll-like receptor (TLR) 4, which has been proposed as a mediator of rheumatoid arthritis (RA). NI-0101 is a first-in-class humanised monoclonal antibody blocking TLR4, as confirmed by inhibition of in vivo lipopolysaccharide-induced cytokine release in healthy volunteers. This study was design to confirm preclinical investigations supporting a biomarker-driven approach for treatment of patients with RA who present positive for these immune complexes.MethodsPlacebo-controlled, double-blind, randomised (2:1) trial of the tolerability and efficacy of NI-0101 (5 mg/kg, every 2 weeks for 12 weeks) versus placebo in ACPA-positive RA patients with inadequate response to methotrexate. Efficacy measures included Disease Activity Score (28-joint count) with C reactive protein (DAS28-CRP), European League Against Rheumatism (EULAR) good and moderate responses, and American College of Rheumatology (ACR) 20, ACR50 and ACR70 responses. Subgroup analyses defined on biomarkers were conducted. Pharmacokinetics, pharmacodynamics and safety were reported.Results90 patients were randomised (NI-0101 (61) and placebo (29)); 86 completed the study. No significant between-group difference was observed for any of the efficacy endpoints. Subgroup analyses using baseline parameters as covariants did not reveal any population responding to NI-0101. Treatment-emergent adverse events occurred in 51.7% of patients who received placebo versus 52.5% for NI-0101.ConclusionsWe demonstrate for the first time that in RA, a human immune-mediated inflammatory disease, blocking the TLR4 pathway alone does not improve disease parameters. Successful targeting of innate immune pathways in RA may require broader and/or earlier inhibitory approaches.

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Direct recognition of LPS drive TLR4 expressing CD8+ T cell activation in patients with rheumatoid arthritis

Cited by 44 publications

References 50 publications

Human Postprandial Nutrient Metabolism and Low-Grade Inflammation: A Narrative Review

Human Postprandial Nutrient Metabolism and Low-Grade Inflammation: A Narrative Review

Managing Rheumatoid Arthritis with Dietary Interventions

Efficacy and safety of NI-0101, an anti-toll-like receptor 4 monoclonal antibody, in patients with rheumatoid arthritis after inadequate response to methotrexate: a phase II study

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