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

Abstract

Biological agents have allowed remarkable improvement in controlling autoimmune arthropathies, although none of the numerous biologics readily available represent a universal treatment standard. Moreover, classical and genetic predictors are currently unsatisfactory to predict individual response to a biologic, and the best treatment 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. A 24-year-old woman was diagnosed with active early rheumatoid arthritis. The initial treatment regimen (prednisone, methotrexate, hydroxychloroquine, naproxen) was inefficient, 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 quantification 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 leukocytes 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. An efficient way to effectively 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 exemplified by this case report.