TLR4 endogenous ligand MRP8/14 level in enthesitis-related arthritis and its association with disease activity and TLR4 expression

Rahman, Mujeeb T; Myles, Arpita; Gaur, Priyanka; Misra, Ramnath; Aggarwal, Amita

doi:10.1093/rheumatology/ket375

Cited by 31 publications

(24 citation statements)

References 20 publications

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“…Hammer et al 18 showed a strong correlation between plasma levels of calprotectin and joint damage in patients with rheumatoid arthritis. Rahman et al 22 reported elevated plasma levels of calprotectin in patients with enthesitis-related arthritis. They suggested that patients with an active disease had higher plasma levels of calprotectin compared with those of control subjects.…”

Section: Discussionmentioning

confidence: 99%

Elevated Serum Levels of Calprotectin (Myeloid-Related Protein 8/14) in Patients with Ankylosing Spondylitis and Its Association with Disease Activity and Quality of Life

Oktayoğlu

Bozkurt

Mete

et al. 2014

Journal of Investigative Medicine

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Our results suggest that calprotectin might play an important role in the pathogenetic mechanisms of AS; however, the calprotectin levels did not correlate with the measurements of disease activity, functional abilities, radiological damage, and the quality of life in these patients. Further insight into this area of research might provide opportunities to develop novel treatment strategies, which take into account the role of these peptides in the pathogenetic mechanisms of AS.

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Section: Discussionmentioning

confidence: 99%

Elevated Serum Levels of Calprotectin (Myeloid-Related Protein 8/14) in Patients with Ankylosing Spondylitis and Its Association with Disease Activity and Quality of Life

Oktayoğlu

Bozkurt

Mete

et al. 2014

Journal of Investigative Medicine

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“…We have shown that endogenous ligands induce proinflammatory response from monocytes in patients and it has been reported that both MRP8/14 and TNC levels are elevated in patients with ERA and AS (12,13,18,21). We studied the production of these ligands on stimulation of monocytes and found that indeed, patients cells produced higher levels of TNC & MRP8/14 as compared to HC.…”

Section: Discussionmentioning

confidence: 91%

“…ERA patients also show gut dysbiosis and presence of autoantibodies associated with inflammation of gastrointestinal mucosa like antibodies to tissue transglutaminase or anti-Saccharomyces cerevisiae antibodies (17). They have elevated fecal calprotectin, high pro-inflammatory cytokines (TNF and IL-6) in synovial fluid (SF) and TLR4 endogenous ligands (TNC and MRP8/14) in serum (18)(19)(20)(21)(22). In addition, they also have increased TLR2 and 4 expression on monocytes in blood and SF (8).…”

Section: Introductionmentioning

confidence: 99%

Patients with enthesitis related arthritis show similar monocyte function pattern as seen in adult axial spondyloarthropathy

2020

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Background: Axial SpA and Enthesitis related arthritis (ERA) patients show strong HLA-B27 association, gut dysbiosis, high toll like receptor (TLR)2 and 4 expression on monocytes, pro-inflammatory cytokine production and elevated levels of TLR4 endogenous ligands [tenascin-c (TNC) and myeloid related protein (MRP)8/14] in serum. Hence, we aimed to understand if these diseases have similar or different monocyte response. Methods: Fifty adult axial SpA, 52 ERA patients and 25 healthy controls (HC) were enrolled. Cytokine-producing monocyte frequency before and after stimulation with lipopolysaccharide (LPS), peptidoglycan (PG), TNC or MRP8 were measured in whole blood (WB) and synovial fluid mononuclear cells (SFMC) by flow cytometry. Also, IL-6, TNF, MMP3, TNC and MRP8/14 levels were measured in unstimulated and TLR ligand stimulated WB cultures supernatant by ELISA. Finally, the mRNA expression levels of TNF and IL-6 were measured post stimulation with LPS, TNC and MRP8. Results: At baseline, ERA and axial SpA patients showed similar TNF-α producing monocyte frequency which was higher than HC. MRP8 simulation led to increased TNF-α producing monocyte frequency in ERA than axial SpA. TNC and MRP8 stimulation led to similar IL-6 producing monocyte frequency in axial SpA and ERA patients. Baseline TNF and IL-6 producing monocyte frequency also modestly correlated with disease activity scores. TNF and IL-6 producing monocyte frequency increased in response to TLR stimulation in SFMC from both patients. In culture supernatants, axial SpA and ERA patients showed similar TNF production at baseline. MRP8 and TNC stimulation led to higher TNF production from ERA. Baseline IL-6 and MMP3 production was higher in ERA while TLR stimulation led to similar IL-6 and MMP3 production from axial SpA and ERA. TNC stimulation led to higher MMP3 production in ERA. mRNA expression in response to TLR stimulation was observed to be similar in axial SpA and ERA. TNC production was higher in ERA at baseline, while MRP8/14 production was higher in axial SpA than ERA post stimulation. Conclusion: ERA patients have similar monocyte response to exogenous and endogenous TLR ligands as patients with axial SpA. This suggests that differences between pediatric and adult-onset SpA are minimal and they may have a common pathogenesis.

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“…Similarly, others have reported increased concentrations of endogenous ligand MRP18/4 in plasma and reduced TLR4 expression (Rahman et al. 2014). The fact we detected soluble forms of TLR2 and TLR4, with the latter being differentially regulated, is further evidence of the importance of TLR4 in inflammatory components/mechanisms associated with OA, which shape the OA disease concept (Houard et al.…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptors and their soluble forms differ in the knee and thumb basal osteoarthritic joints

et al. 2017

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Background and purposeAlthough the pathogenesis of osteoarthritis (OA) is not well understood, chondrocyte-mediated inflammatory responses (triggered by the activation of innate immune receptors by damage-associated molecules) are thought to be involved. We examined the relationship between Toll-like receptors (TLRs) and OA in cartilage from 2 joints differing in size and mechanical loading: the first carpometacarpal (CMC-I) and the knee.Patients and methodsSamples of human cartilage obtained from OA CMC-I and knee joints were immunostained for TLRs (1–9) and analyzed using histomorphometry and principal component analysis (PCA). mRNA expression levels were analyzed with RT-PCR. Collected synovial fluid (SF) samples were screened for the presence of soluble forms of TLR2 and TLR4 by enzyme-linked immunosorbent assay (ELISA).ResultsIn contrast to knee OA, TLR expression in CMC-I OA did not show grade-dependent overall profile changes, but PCA revealed that TLR expression profiles clustered according to their cellular compartment organization. Protein levels of TLR4 were substantially higher in knee OA than in CMC-I OA, while the opposite was the case at the mRNA level. ELISA assays confirmed the presence of soluble forms of TLR2 and TLR4 in SF, with sTLR4 being considerably higher in CMC-I OA than in knee OA.InterpretationWe observed that TLRs are differentially expressed in OA cartilage, depending on the joint. Soluble forms of TLR2 and TLR4 were detected for the first time in SF of osteoarthritic joints, with soluble TLR4 being differentially expressed. Together, our results suggest that negative regulatory mechanisms of innate immunity may be involved in the pathomolecular mechanisms of osteoarthritis.

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TLR4 endogenous ligand MRP8/14 level in enthesitis-related arthritis and its association with disease activity and TLR4 expression

Abstract: MRP8/14 levels are increased in the plasma of ERA patients and are higher in those with active disease and the levels decrease in patients who respond to treatment, suggesting that it may be a good biomarker during follow-up.

Cited by 31 publications

References 20 publications

Elevated Serum Levels of Calprotectin (Myeloid-Related Protein 8/14) in Patients with Ankylosing Spondylitis and Its Association with Disease Activity and Quality of Life

Elevated Serum Levels of Calprotectin (Myeloid-Related Protein 8/14) in Patients with Ankylosing Spondylitis and Its Association with Disease Activity and Quality of Life

Patients with enthesitis related arthritis show similar monocyte function pattern as seen in adult axial spondyloarthropathy

Toll-like receptors and their soluble forms differ in the knee and thumb basal osteoarthritic joints

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