Serum Calprotectin Discriminates Subclinical Disease Activity from Ultrasound-Defined Remission in Patients with Rheumatoid Arthritis in Clinical Remission

Jana Hurnakova, Hana Hulejova, Jakub Zavada, Martin Komarc, Petra Hanova, Martin Klein, Herman Mann, Olga Sleglova, Marta Olejarova, Sarka Forejtova, Olga Ruzickova, Jiri Vencovsky, Karel Pavelka, Ladislav Senolt, Jana Hurnakova, Hana Hulejova, Jakub Zavada, Martin Komarc, Petra Hanova, Martin Klein, Herman Mann, Olga Sleglova, Marta Olejarova, Sarka Forejtova, Olga Ruzickova, Jiri Vencovsky, Karel Pavelka, Ladislav Senolt

Abstract

Objective: Clinical remission in some patients with rheumatoid arthritis (RA) may be associated with ongoing synovial inflammation that is not always detectable on clinical examination or reflected by laboratory tests but can be visualized by musculoskeletal ultrasound. The goal of our study was to determine the levels of serum calprotectin, a major leukocyte protein, in patients with RA in clinical remission and to investigate the ability of serum calprotectin levels to distinguish patients in ultrasound-defined remission from those with residual ultrasound subclinical inflammation.

Methods: Seventy RA patients in clinical remission underwent clinical and ultrasound examination. Ultrasound examination was performed according to the German US7 score. Ultrasound remission was defined as grey scale (GS) range 0-1 and power Doppler (PD) range 0. The levels of serum calprotectin and C-reactive protein (CRP) were determined. The discriminatory capacity of calprotectin and CRP in detecting residual ultrasound inflammation was assessed using ROC curves.

Results: The total number of patients fulfilling the DAS28-ESR, DAS28-CRP, SDAI and CDAI remission criteria was 58, 67, 32 and 31, respectively. Residual synovial inflammation was found in 58-67% of the patients who fulfilled at least one set of clinical remission criteria. Calprotectin levels were significantly higher in patients with residual synovial inflammation than in those with ultrasound-defined remission (mean 2.5±1.3 vs. 1.7±0.8 μg/mL, p<0.005). Using ultrasound-defined remission criteria, calprotectin had an AUC of 0.692, p<0.05 using DAS28-ESR remission criteria and an AUC of 0.712, p<0.005 using DAS28-CRP remission criteria. Calprotectin correctly distinguished ultrasound remission from subclinical activity in 70% of patients. CRP (AUC DAS28-ESR = 0.494, p = NS; AUC DAS28-CRP = 0.498, p = NS) had lower and insignificant discriminatory capacity.

Conclusion: The present study demonstrates the potential of calprotectin to distinguish RA patients in both clinical and ultrasound-defined remission from patients in clinical remission but with residual subclinical disease activity.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Presence of ultrasound findings in…
Fig 1. Presence of ultrasound findings in RA patients in clinical remission.
(A) Percentage of patients fulfilling the ultrasound remission criteria. (B) Presence of positive GS and PD ultrasound findings.
Fig 2. Box-plots showing levels of serum…
Fig 2. Box-plots showing levels of serum calprotectin and CRP in patients who achieved clinical remission according to a) DAS28-ESR and b) DAS28-CRP.
Fig 3. Receiver-operator characteristic curves of serum…
Fig 3. Receiver-operator characteristic curves of serum calprotectin and CRP for distinguishing patients with ultrasound remission from those with subclinical ultrasound activity.
All the patients achieved clinical remission according to a) DAS28-ESR, b) DAS28-CRP, c) SDAI and d) CDAI criteria.

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