Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 May 30;15(11):2984.
doi: 10.3390/cancers15112984.

Calprotectin in Patients with Rheumatic Immunomediated Adverse Effects Induced by Checkpoints Inhibitors

Beatriz Frade-Sosa  1 , Chafik Alejandro Chacur  1 , Josep M Augé  2 , Andrés Ponce  1 , Juan C Sarmiento-Monroy  1 , Ana Belén Azuaga  1 , Nuria Sapena  1 , Julio Ramírez  1 , Virginia Ruiz-Esquide  1 , Rosa Morlà  1 , Sandra Farietta  1 , Patricia Corzo  1 , Juan D Cañete  1 , Raimon Sanmartí  1 , José A Gómez-Puerta  1
Affiliations

Calprotectin in Patients with Rheumatic Immunomediated Adverse Effects Induced by Checkpoints Inhibitors

Beatriz Frade-Sosa et al. Cancers (Basel). .

Abstract

Background: this is an exploratory study to evaluate calprotectin serum levels in patients with rheumatic immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) treatment.

Methods: this is a retrospective observational study including patients with irAEs rheumatic syndromes. We compared the calprotectin levels to those in a control group of patients with RA and with a control group of healthy individuals. Additionally, we included a control group of patients treated with ICI but without irAEs to check calprotectin levels. We also analysed the performance of calprotectin for the identification of active rheumatic disease using receiver operating characteristic curves (ROC).

Results: 18 patients with rheumatic irAEs were compared to a control group of 128 RA patients and another group of 29 healthy donors. The mean calprotectin level in the irAE group was 5.15 μg/mL, which was higher than the levels in both the RA group (3.19 μg/mL) and the healthy group (3.81 μg/mL) (cut-off 2 μg/mL). Additionally, 8 oncology patients without irAEs were included. In this group, calprotectin levels were similar to those of the healthy controls. In patients with active inflammation, the calprotectin levels in the irAE group were significantly higher (8.43 μg/mL) compared to the RA group (3.94 μg/mL). ROC curve analysis showed that calprotectin had a very good discriminatory capacity to identify inflammatory activity in patients with rheumatic irAEs (AUC of 0.864).

Conclusions: the results suggest that calprotectin may serve as a marker of inflammatory activity in patients with rheumatic irAEs induced by treatment with ICIs.

Keywords: calprotectin; immune checkpoint inhibitors; immune-related adverse events; rheumatoid arthritis.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Diagram representing calprotectin levels in the groups. Rhombus represent ICI + irAEs: immune checkpoint inhibitors with rheumatic immune-related adverse event; circles represent RA: rheumatoid arthritis. Square represents ICI without irAEs: immune checkpoint inhibitor control group. Triangle represents control: healthy donors. Calprotectin levels (μg/mL). Statistical significance was reached when comparing the calprotectin levels between the main group (ICI + irAEs) and the control group of oncologic patients without irAEs (p-value 0.49, calculated with the Mann–Whitney test).
Figure 2
Figure 2
Calprotectin levels in relation to inflammatory arthritis at the time of determination. Circles represent RA: rheumatoid arthritis. Squares represent ICI + irAEs: immune checkpoint inhibitors plus irAEs. Calprotectin levels (μg/mL).
Figure 3
Figure 3
ROC curves of blood biomarkers for inflammatory activity in patients with rheumatic irAEs. (a) ROC curve of ESR, (b) ROC curve of CRP, (c) ROC curve of serum calprotectin. AUC: area under the curve. ESR: erythrocyte sedimentation rate, CRP: C-reactive protein.
Figure 4
Figure 4
ROC curves of combined calprotectin, CRP, and ESR for inflammatory activity in patients with musculoskeletal irAEs. AUC: area under the curve. ESR: erythrocyte sedimentation rate. CRP: C-reactive protein.
See this image and copyright information in PMC

References

    1. Rotte A., Jin J.Y., Lemaire V. Mechanistic Overview of Immune Checkpoints to Support the Rational Design of Their Combinations in Cancer Immunotherapy. Ann. Oncol. 2018;29:71–83. doi: 10.1093/annonc/mdx686. - DOI - PubMed
    1. Richter M.D., Crowson C., Kottschade L.A., Finnes H.D., Markovic S.N., Thanarajasingam U. Rheumatic Syndromes Associated With Immune Checkpoint Inhibitors: A Single-Center Cohort of Sixty-One Patients. Arthritis Rheumatol. 2019;71:468–475. doi: 10.1002/art.40745. - DOI - PubMed
    1. Calabrese C., Kirchner E., Kontzias A., Velcheti V., Calabrese L.H. Correction: Rheumatic Immune-Related Adverse Events of Checkpoint Therapy for Cancer: Case Series of a New Nosological Entity. RMD Open. 2017;3:e000412corr1. doi: 10.1136/rmdopen-2016-000412. - DOI - PMC - PubMed
    1. Kostine M., Rouxel L., Barnetche T., Veillon R., Martin F., Dutriaux C., Dousset L., Pham-Ledard A., Prey S., Beylot-Barry M., et al. Rheumatic Disorders Associated with Immune Checkpoint Inhibitors in Patients with Cancer-Clinical Aspects and Relationship with Tumour Response: A Single-Centre Prospective Cohort Study. Ann. Rheum. Dis. 2018;77:393–398. doi: 10.1136/annrheumdis-2017-212257. - DOI - PubMed
    1. Mooradian M.J., Nasrallah M., Gainor J.F., Reynolds K.L., Cohen J.V., Lawrence D.P., Miloslavsky E.M., Kohler M.J., Sullivan R.J., Schoenfeld S.R. Musculoskeletal Rheumatic Complications of Immune Checkpoint Inhibitor Therapy: A Single Center Experience. Semin. Arthritis Rheum. 2019;48:1127–1132. doi: 10.1016/j.semarthrit.2018.10.012. - DOI - PubMed

LinkOut - more resources