Background/Purpose: Calprotectin is a protein highly expressed in myeloid cells and its elevated presence in blood, and the GI tract is associated with immune mediated inflammatory diseases. In autoimmune diseases such as rheumatoid arthritis (RA), elevated levels of calprotectin have been previously reported in patient serum. Furthermore, calprotectin is often associated with neutrophil-mediated inflammation, and in RA disproportionate neutrophil activation exacerbates disease progression with associated elevated calprotectin levels in affected patients. This study aimed to evaluate the utility of calprotectin as a biomarker for monitoring response to different treatments in two longitudinal cohorts of RA patients.

Methods: Serum samples stored at -80°C were obtained from the biobanks of Reade and Radboud University Medical Centre (RUMC). A total of 231 RA serum samples from 33 participants across seven time points over a one-year follow-up period were collected from Reade, while 153 RA samples from 36 participants at various time points over a similar period were obtained from RUMC. At baseline, all samples in the Reade cohort were from treatment-naïve participants, whereas in the RUMC cohort two participants had prior treatment. Throughout consecutive sampling, patients underwent various DMARD treatments. Calprotectin levels were measured using the R&D Biosystems S100A8/A9 ELISA kit following the manufacturer’s protocol. Data analysis was performed using Prism 10 and Spotfire Desktop Analyst software, and statistical analysis was performed using the Friedman test.

Results: Baseline calprotectin levels showed a gradual decline following the introduction of treatment. In both cohorts, stratification based on treatment response revealed a significantly greater reduction in calprotectin levels among responders compared to non-responders. In the Reade cohort, the median calprotectin level decreased from 4270 ng/ml at baseline to 1812 ng/ml after one year (p < 0.01), while in the RUMC cohort, it dropped from 5498 to 2021 ng/ml over a similar period (p < 0.01). In contrast, non-responders exhibited minimal changes, with median values shifting from 2920 to 2822 ng/ml in the Reade cohort and from 2413 to 2670 ng/ml in the RUMC cohort over one year. Furthermore, the change or delta calprotectin showed a positive correlation with delta CRP (R=0.55), delta ESR (R=0.61) and delta DAS28-CRP (R=0.37).

Conclusion: Our data obtained from the analyses of two longitudinal RA cohorts demonstrate that serum calprotectin and its change can be used as a biomarker for disease activity and response to treatment. Citryll is developing a novel antibody therapeutic mAb (CIT-013) that targets release of extracellular traps from neutrophils. It is our intention to further probe the utility of calprotectin, along with other conventionally used endpoints, as a marker of response to therapy in an RA phase 2a proof of concept study which will begin in 2025.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/calprotectin-serum-levels-a-potential-neutrophil-activation-biomarker-to-monitor-treatment-response-in-rheumatoid-arthritis/