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Background:Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects synovial joints, leading to inflammation, joint destruction, loss of function, and disability. Although recent pharmaceutical advances have improved treatment of RA, patients with RA often inquire about dietary interventions to improve RA symptoms, as they perceive rapid changes in their symptoms after consumption of certain foods. There is evidence that some ingredients have pro- or anti-inflammatory effects. In addition, recent literature has shown a link between diet and microbiome changes. Both diet and the gut microbiome are linked to circulating metabolites that may modulate inflammation. However, evidence of the effects of an anti-inflammatory and probiotic-rich diet in patients with RA is scarce. There is also a need for biological data to support its anti-inflammatory effects. Methods:The main goal of this study is to delineate the design process for a diet tailored to our RA population. To achieve this goal, we collected information on diet, supplements, cooking methods, and intake of different ingredients for each patient. Different groups were interviewed, and their feedback was assessed to design a diet that incorporates suggested anti-inflammatory ingredients in a manner that was easy for patients to adopt based on their lifestyles and backgrounds. Results:We designed a diet that includes a high intake of potential anti-inflammatory ingredients. Feedback from highly motivated patients was critical in constructing an anti-inflammatory diet (ITIS diet) with elevated adherence. Conclusion:In order to tailor our diet, we surveyed our patients on several different parameters. We obtained important feedback on how feasible our ITIS diet is for RA patients. Using this feedback, we made minor improvements and finalized the design of the ITIS diet. This diet is being used in an on-going pilot study to determine their anti-inflammatory effect in pain and joint swelling in

BackgroundRheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects synovial joints, leading to inflammation, joint destruction, loss of function, and disability. Although recent pharmaceutical advances have improved treatment of RA, patients with RA often inquire about dietary interventions to improve RA symptoms, as they perceive rapid changes in their symptoms after consumption of certain foods. There is evidence that some ingredients have pro- or anti-inflammatory effects. In addition, recent literature has shown a link between diet and microbiome changes. Both diet and the gut microbiome are linked to circulating metabolites that may modulate inflammation. However, evidence of the effects of an anti-inflammatory and probiotic-rich diet in patients with RA is scarce. There is also a need for biological data to support its anti-inflammatory effects.MethodsThe main goal of this study is to delineate the design process for a diet tailored to our RA population. To achieve this goal, we collected information on diet, supplements, cooking methods, and intake of different ingredients for each patient. Different groups were interviewed, and their feedback was assessed to design a diet that incorporates suggested anti-inflammatory ingredients in a manner that was easy for patients to adopt based on their lifestyles and backgrounds.ResultsWe designed a diet that includes a high intake of potential anti-inflammatory ingredients. Feedback from highly motivated patients was critical in constructing an anti-inflammatory diet (ITIS diet) with elevated adherence.ConclusionIn order to tailor our diet, we surveyed our patients on several different parameters. We obtained important feedback on how feasible our ITIS diet is for RA patients. Using this feedback, we made minor improvements and finalized the design of the ITIS diet. This diet is being used in an on-going pilot study to determine their anti-inflammatory effect in pain and joint swelling in RA pati

ObjectivesRecent studies indicate that glucose metabolism is altered in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Hexokinases (HKs) catalyse the first step in glucose metabolism, and HK2 constitutes the principal HK inducible isoform. We hypothesise that HK2 contributes to the synovial lining hypertrophy and plays a critical role in bone and cartilage damage.MethodsHK1 and HK2 expression were determined in RA and osteoarthritis (OA) synovial tissue by immunohistochemistry. RA FLS were transfected with either HK1 or HK2 siRNA, or infected with either adenovirus (ad)-GFP, ad-HK1 or ad-HK2. FLS migration and invasion were assessed. To study the role of HK2 in vivo, 108 particles of ad-HK2 or ad-GFP were injected into the knee of wild-type mice. K/BxN serum transfer arthritis was induced in HK2F/F mice harbouring Col1a1-Cre (HK2Col1), to delete HK2 in non-haematopoietic cells.ResultsHK2 is particular of RA histopathology (9/9 RA; 1/8 OA) and colocalises with FLS markers. Silencing HK2 in RA FLS resulted in a less invasive and migratory phenotype. Consistently, overexpression of HK2 resulted in an increased ability to migrate and invade. It also increased extracellular lactate production. Intra-articular injection of ad-HK2 in normal knees dramatically increased synovial lining thickness, FLS activation and proliferation. HK2 was highly expressed in the synovial lining after K/BxN serum transfer arthritis. HK2Col1 mice significantly showed decreased arthritis severity, bone and cartilage damage.ConclusionHK2 is specifically expressed in RA synovial lining and regulates FLS aggressive functions. HK2 might be an attractive selective metabolic target safer than global glycolysis for RA treatment.

An increasing number of studies show how changes in intracellular metabolic pathways alter tumor and immune cell function. However, little information about metabolic changes in other cell types, including synovial fibroblasts, is available. In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) are the most common cell type at the pannus-cartilage junction and contribute to joint destruction through their production of cytokines, chemokines, and matrix-degrading molecules and by migrating and invading joint cartilage. In this review, we show that these cells differ from healthy synovial fibroblasts, not only in their marker expression, proto-oncogene expression, or their epigenetic changes, but also in their intracellular metabolism. These metabolic changes must occur due to the stressful microenvironment of inflamed tissues, where concentrations of crucial nutrients such as glucose, glutamine, and oxygen are spatially and temporally heterogeneous. In addition, these metabolic changes will increase metabolite exchange between fibroblast and other synovial cells, which can potentially be activated. Glucose and phospholipid metabolism as well as bioactive lipids, including sphingosine-1-phosphate and lysophosphatidic acid, among others, are involved in FLS activation. These metabolic changes likely contribute to FLS involvement in aspects of immune response initiation or abnormal immune responses and strongly contribute to joint destruction.

An increasing number of studies show how changes in intracellular metabolic pathways alter tumor and immune cell function. However, little information about metabolic changes in other cell types, including synovial fibroblasts, is available. In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) are the most common cell type at the pannus-cartilage junction and contribute to joint destruction through their production of cytokines, chemokines, and matrix-degrading molecules and by migrating and invading joint cartilage. In this review, we show that these cells differ from healthy synovial fibroblasts, not only in their marker expression, proto-oncogene expression, or their epigenetic changes, but also in their intracellular metabolism. These metabolic changes must occur due to the stressful microenvironment of inflamed tissues, where concentrations of crucial nutrients such as glucose, glutamine, and oxygen are spatially and temporally heterogeneous. In addition, these metabolic changes will increase metabolite exchange between fibroblast and other synovial cells, which can potentially be activated. Glucose and phospholipid metabolism as well as bioactive lipids, including sphingosine-1-phosphate and lysophosphatidic acid, among others, are involved in FLS activation. These metabolic changes likely contribute to FLS involvement in aspects of immune response initiation or abnormal immune responses and strongly contribute to joint destruction.