The use of leukocytes’ secretome to individually target biological therapy in autoimmune arthritis : a case report

Authors: Poubelle, PatricePagé, NathalieLongchamps, Marie-Pier; Sampaio Moura, Natalia; Beck, David B.; Aksentijevich, Ivona; Tessier, PhilippePelletier, Martin
Abstract: Background: Biological agents have allowed remarkable improvement in controlling autoimmune arthropathies, although none of the numerous biologics readily available represent a universal treatment standard. Moreover, classi‑ cal and genetic predictors are currently unsatisfactory to predict individual response to a biologic, and the best treat‑ ment selection is still based on a trial-and-error approach. Here, we report a clinical case demonstrating the usefulness of examining the leukocytes’ secretome of patients. We set up and standardized a protocol that examines a patient’s immune responses to establish the secretome of the blood mononuclear leukocytes and personalize the biotherapy. Case presentation: A 24-year-old woman was diagnosed with active early rheumatoid arthritis. The initial treat‑ ment regimen (prednisone, methotrexate, hydroxychloroquine, naproxen) was inefcient, as well as the anti-TNF adalimumab. The diagnosis was revised as possible rheumatoid arthritis-like psoriatic arthritis and adalimumab was replaced by abatacept (IgG1 Fc-CTLA-4) to no avail. Five years later, abatacept was replaced by the anti-IL-12/ IL-23 ustekinumab with no objective control over the symptoms. The patient was thus enrolled in a prospective study based on the quantifcation of cytokines secreted by peripheral blood leukocytes stimulated with well-known immune activators of pattern recognition receptors and cytokine signalling. The results of this study revealed that plasma concentrations of cytokines were similar between the patient and healthy donors. In comparison to leuko‑ cytes from healthy donors, the patient’s secretome showed a unique overproduction of IL-6. The anti-IL-6 receptor tocilizumab was, therefore, administered with a rapid improvement of her active psoriatic arthritis that remained dependent on low prednisone dosage. Clinical parameters progressively returned to normal levels and her quality of life was greatly improved, despite the major delay to begin the present personalized treatment. Conclusions: An efcient way to efectively treat patients with complex autoimmune arthropathies, and avoid irreversible disability, is to know their leukocytes’ secretome to identify abnormally secreted cytokines and personalize their biotherapy, as exemplifed by this case report.
Document Type: Article de recherche
Issue Date: 5 June 2019
Open Access Date: 7 June 2019
Document version: VoR
Creative Commons Licence:
This document was published in: Clinical and Translational Medicine, 8:19 (2019)
Alternative version: 10.1186/s40169-019-0236-7
Collection:Articles publiés dans des revues avec comité de lecture

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