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Circulating calprotectin (S100A8/A9) is higher in rheumatoid arthritis patients that relapse within 12 months of tapering anti-rheumatic drugs.

ABSTRACT: OBJECTIVE:To investigate whether calprotectin (S100A8/A9 or MRP8/14), an inflammatory complex released by monocytes, could indicate residual subclinical inflammation in rheumatoid arthritis (RA) patients who are in stable remission on disease-modifying anti-rheumatic drugs (DMARDs) and serve as a marker for disease flare after DMARD tapering. METHODS:We used data from two trials. Patients from the IMPROVED study had early (< 2 years) RA, and when they achieved disease activity score remission (DAS44 < 1.6), they stopped methotrexate to attempt drug-free remission. Patients from the RETRO study had established RA in stable remission (DAS28 < 2.6) and either tapered by 50% or stopped (biological or conventional) DMARDs. Circulating calprotectin at the tapering time point was determined by ELISA, and its predictive value for flare (loss of remission) within 12 months of DMARD tapering/stopping was determined. RESULTS:In both IMPROVED (n = 104) and RETRO (n = 57), patients that flared within 12 months had higher calprotectin at the moment of DMARD tapering/stopping. Twofold higher calprotectin at the moment of DMARD tapering/stopping was associated with an increased risk (odds ratio) of flare of 1.07 (95% CI 0.98-1.18, p = 0.14) in the IMPROVED and 3.62 (95% CI 1.76-7.46, p < 0.001) in the RETRO. Correcting for clinical predictors of flare (DAS at study inclusion, anti-CCP2 positivity, gender) did not change these estimates. The area under the receiver operating curve of calprotectin levels for predicting flare within 12 months was 0.63 (95% CIs 0.51-0.76) in the IMPROVED study and 0.80 (95% CIs 0.69 to 0.92) in the RETRO study. CONCLUSION:Circulating calprotectin levels in RA patients in remission on DMARDs are higher in patients that will flare upon DMARD tapering/stopping. Since the differences between the cohorts precluded definitive conclusions, more research is needed to determine whether calprotectin has prognostic value in predicting flare after attempting drug tapering in RA. TRIAL REGISTRATION:IMPROVED, ISRCTN11916566. RETRO, 2009-015740-42.

SUBMITTER: de Moel EC

PROVIDER: S-EPMC6894482 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Circulating calprotectin (S100A8/A9) is higher in rheumatoid arthritis patients that relapse within 12 months of tapering anti-rheumatic drugs.

de Moel Emma C EC Rech Jürgen J Mahler Michael M Roth Johannes J Vogl Thomas T Schouffoer Anne A Goekoop Robbert J RJ Huizinga Tom W J TWJ Allaart Cornelia F CF Toes René E M REM Schett Georg G van der Woude Diane D

Arthritis research & therapy 20191205 1

<h4>Objective</h4>To investigate whether calprotectin (S100A8/A9 or MRP8/14), an inflammatory complex released by monocytes, could indicate residual subclinical inflammation in rheumatoid arthritis (RA) patients who are in stable remission on disease-modifying anti-rheumatic drugs (DMARDs) and serve as a marker for disease flare after DMARD tapering.<h4>Methods</h4>We used data from two trials. Patients from the IMPROVED study had early (< 2 years) RA, and when they achieved disease activity sco ...[more]

PMID: 31805992

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Project description:BackgroundTyphoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8) and S100A9 (MRP14) form bioactive antimicrobial heterodimers (calprotectin) that can activate Toll-like receptor 4, promoting lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize the expression and function of S100A8/A9 in patients with typhoid fever and in a murine invasive Salmonella model.Methods and principal findingsS100A8/A9 protein levels were determined in acute phase plasma or feces from 28 Bangladeshi patients, and convalescent phase plasma from 60 Indonesian patients with blood culture or PCR-confirmed typhoid fever, and compared to 98 healthy control subjects. To functionally characterize the role of S100A8/A9, we challenged wildtype (WT) and S100A9-/- mice with S. Typhimurium and determined bacterial loads and inflammation 2- and 5- days post infection. We further assessed the antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi replication in vitro. Typhoid fever patients demonstrated a marked increase of S100A8/A9 in acute phase plasma and feces and this increases correlated with duration of fever prior to admission. S100A8/A9 directly inhibited the growth of S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both the liver and the systemic compartment but S100A9-/- mice were indistinguishable from WT mice with respect to bacterial growth, survival, and inflammatory responses, as determined by cytokine release, histopathology and organ injury.ConclusionS100A8/A9 is markedly elevated in human typhoid, correlates with duration of fever prior to admission and directly inhibits the growth of S. Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive Salmonella model, S100A8/A9 does not contribute to an effective host response against S. Typhimurium in mice.

Dataset Information

Circulating calprotectin (S100A8/A9) is higher in rheumatoid arthritis patients that relapse within 12 months of tapering anti-rheumatic drugs.

Publications

Circulating calprotectin (S100A8/A9) is higher in rheumatoid arthritis patients that relapse within 12 months of tapering anti-rheumatic drugs.

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