Effects of a 15-month anti-TNF-α treatment on plasma levels of glycosaminoglycans in women with rheumatoid arthritis

Szeremeta, Anna; Jura-Półtorak, Agnieszka; Koźma, Ewa M; Głowacki, Andrzej; Kucharz, Eugene J.; Kopeć-Mędrek, Magdalena; Olczyk, Krystyna

doi:10.1186/s13075-018-1711-z

Cited by 14 publications

(15 citation statements)

References 47 publications

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“…(4) Glycosaminoglycans (GAGs) are major components of joint cartilage and other soft connective tissues. Modification of GAG metabolism may play a crucial role in RA pathogenesis 32. These results suggest that the aforementioned substances in the gut could influence the pathology of RA.…”

Section: Resultsmentioning

confidence: 90%

Metagenome-wide association study of gut microbiome revealed novel aetiology of rheumatoid arthritis in the Japanese population

et al. 2019

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ObjectiveThe causality and pathogenic mechanism of microbiome composition remain elusive in many diseases, including autoimmune diseases such as rheumatoid arthritis (RA). This study aimed to elucidate gut microbiome’s role in RA pathology by a comprehensive metagenome-wide association study (MWAS).MethodsWe conducted MWAS of the RA gut microbiome in the Japanese population (n case=82, n control=42) by using whole-genome shotgun sequencing of high depth (average 13 Gb per sample). Our MWAS consisted of three major bioinformatic analytic pipelines (phylogenetic analysis, functional gene analysis and pathway analysis).ResultsPhylogenetic case–control association tests showed high abundance of multiple species belonging to the genus Prevotella (e.g., Prevotella denticola) in the RA case metagenome. The non-linear machine learning method efficiently deconvoluted the case–control phylogenetic discrepancy. Gene functional assessments showed that the abundance of one redox reaction-related gene (R6FCZ7) was significantly decreased in the RA metagenome compared with controls. A variety of biological pathways including those related to metabolism (e.g., fatty acid biosynthesis and glycosaminoglycan degradation) were enriched in the case–control comparison. A population-specific link between the metagenome and host genome was identified by comparing biological pathway enrichment between the RA metagenome and the RA genome-wide association study results. No apparent discrepancy in alpha or beta diversities of metagenome was found between RA cases and controls.ConclusionOur shotgun sequencing-based MWAS highlights a novel link among the gut microbiome, host genome and pathology of RA, which contributes to our understanding of the microbiome’s role in RA aetiology.

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Section: Resultsmentioning

confidence: 90%

Metagenome-wide association study of gut microbiome revealed novel aetiology of rheumatoid arthritis in the Japanese population

et al. 2019

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“…The mean age of participants was around 50 years in the PE and PE/RA groups, which agrees with some studies describing the presence and progress of PE and RA between the fourth and fifth decade of life. It has also been reported that women and those aged 40–50 are two to three times more likely to suffer from RA than men . Although there is a postulation that genetic and environmental factors favor the development of both diseases, further studies are needed to prove this hypothesis.…”

Section: Frequency Of F Alocis D Pneumosintes and Both Bacteria Imentioning

confidence: 99%

“…It has also been reported that women and those aged 40-50 are two to three times more likely to suffer from RA than men. [15][16][17][18] Although there is a postulation that genetic and environmental factors favor the development of both diseases, further studies are needed to prove this hypothesis. RA was diagnosed by a rheumatologist in accordance with the criteria of the American College of Rheumatology and European League Against Rheumatism established in 2010.…”

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confidence: 99%

Filifactor alocis and Dialister pneumosintes in a Mexican population affected by periodontitis and rheumatoid arthritis: An exploratory study

Áyala-Herrera

Patrón

Martínez

et al. 2019

Microbiology and Immunology

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“…To the best of our knowledge, no data regarding the effects of anti-TNF-α treatment on biochemical markers of aggrecan turnover in patients with RA has been published so far. Moreover, we have expanded our previous results regarding positive changes in extracellular matrix remodeling in RA patients treated with TNFαI [26].…”

Section: Discussionmentioning

confidence: 65%

Aggrecan Turnover in Women with Rheumatoid Arthritis Treated with TNF-α Inhibitors

Szeremeta

Jura-Półtorak

Zoń‐Giebel³

et al. 2020

JCM

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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.

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Effects of a 15-month anti-TNF-α treatment on plasma levels of glycosaminoglycans in women with rheumatoid arthritis

Cited by 14 publications

References 47 publications

Metagenome-wide association study of gut microbiome revealed novel aetiology of rheumatoid arthritis in the Japanese population

Metagenome-wide association study of gut microbiome revealed novel aetiology of rheumatoid arthritis in the Japanese population

Filifactor alocis and Dialister pneumosintes in a Mexican population affected by periodontitis and rheumatoid arthritis: An exploratory study

Aggrecan Turnover in Women with Rheumatoid Arthritis Treated with TNF-α Inhibitors

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