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Inciarte-Mundo, JoseAuthorRamirez, JulioAuthorRuiz-Esquide, VirginiaAuthorCuervo, AndreaAuthorPascal, MarionaAuthorYaguee, JordiAuthorCanete, Juan DAuthorSanmarti, RaimonCorresponding Author

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March 5, 2025
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Calprotectin and TNF trough serum levels identify power Doppler ultrasound synovitis in rheumatoid arthritis and psoriatic arthritis patients in remission or with low disease activity

Publicated to: ARTHRITIS RESEARCH & THERAPY. 18 160- - 2016-07-08 18(), DOI: 10.1186/s13075-016-1032-z

Authors:

Inciarte-Mundo, Jose; Ramirez, Julio; Victoria Hernandez, Maria; Ruiz-Esquide, Virginia; Cuervo, Andrea; Raquel Cabrera-Villalba, Sonia; Pascal, Mariona; Yaguee, Jordi; Canete, Juan D; Sanmarti, Raimon
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Affiliations

Univ Barcelona, Hosp Clin, Dept Immunol, E-08036 Barcelona, Spain - Author
Univ Barcelona, Hosp Clin, Dept Rheumatol, Carrer Villarroel 170, E-08036 Barcelona, Spain - Author

Abstract

Background: Serum levels of calprotectin, a major S100 leucocyte protein, are associated with disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients. Higher drug trough serum levels are associated with good response in patients treated with tumour necrosis factor inhibitors (TNFi). Power Doppler ultrasound (PDUS) synovitis is predictive of flare and progression of structural damage in patients in clinical remission. The purpose of this study was to analyse the accuracy of calprotectin and TNFi trough serum levels in detecting PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity who were receiving TNFi. Methods: We conducted a cross-sectional study of 92 patients (42 with RA, 50 with PsA) receiving adalimumab (ADA), etanercept (ETN) or infliximab who were in remission or had low disease activity (28-joint Disease Activity Score based on erythrocyte sedimentation rate < 3.2). Associations of calprotectin, TNFi trough serum levels and acute phase reactants with PDUS synovitis were assessed using correlation and linear regression analyses. The accuracy and discriminatory capacity in detecting PDUS synovitis was assessed using ROC curves. Results: PDUS synovitis was found in 62.4 % of RA patients and 32 % of PsA patients. Both RA and PsA patients with PDUS synovitis had higher calprotectin levels and lower TNFi trough serum levels. Calprotectin positively correlated with ultrasound scores (all r coefficients > 0.50 in RA). Calprotectin correlated with the PDUS synovitis score in patients treated with ADA and ETN. Using PDUS synovitis (yes or no) as the reference variable, calprotectin had an AUC of 0.826. The best cut-off was >= 1.66 mu g/ml, with a likelihood ratio of 2.77. C-reactive protein (AUC 0.673) and erythrocyte sedimentation rate (AUC 0.731) had a lower discriminatory capacity. TNFi trough serum levels were significantly associated with PDUS synovitis (OR 0.67, 95 % CI 0.52-0.85, p < 0.001) but their accuracy (AUC < 0.5) was less than that of calprotectin. TNFi trough serum levels were inversely correlated with calprotectin and PDUS synovitis in RA and PsA patients receiving ADA and ETN. Conclusions: Calprotectin and TNFi trough serum levels may help identify PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity.
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Keywords

calprotectindisease activitypsoriatic arthritisrheumatoid arthritistnfi trough serum levelsAcute-phase reactantsAdalimumabAdultAgedAged, 80 and overAntibodieAntirheumatic agentsArthritis, psoriaticArthritis, rheumatoidAssociationBiomarkersCalprotectinClinical remissionClinical-responseCross-sectional studiesDisease activityEnzyme-linked immunosorbent assayEtanerceptFemaleHumansInfliximabJoint inflammationLeukocyte l1 antigen complexMaleMiddle agedMusculoskeletal ultrasoundProgressionProteinPsoriatic arthritiPsoriatic arthritisRheumatoid arthritisSynovitisTask-forceTnfi trough serum levelsTumor necrosis factor-alphaUltrasonographyUltrasonography, dopplerUltrasoundValidation

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal ARTHRITIS RESEARCH & THERAPY due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2016, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Rheumatology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.39. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2026-04-03, the following number of citations:

  • WoS: 46
  • Scopus: 24
  • Europe PMC: 26
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-03:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 102.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 106 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 3.
  • The number of mentions on the social network Facebook: 2 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 3 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
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Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Inciarte Mundo, Jose Esteban) and Last Author (Sanmartí Sala, Raimon).

the author responsible for correspondence tasks has been Sanmartí Sala, Raimon.

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Awards linked to the item

This work was supported by the Hospital Clinic of Barcelona (grant "Emili Letang 2013") and the Catalan Society of Rheumatology (research grant 2013).
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