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

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, 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. Case presentation 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. Conclusions 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.

Ex vivo cytokine production in psoriatic disease: Towards specific signatures in cutaneous psoriasis and peripheral psoriatic arthritis

“…Comparison of the cytokine profiles of the different clinical phenotypes of PsD patients demonstrated features distinctive to each subtype. In PsO patients, our results confirm previous studies highlighting the pivotal role of monocytes and their cytokines (IL-1α, IL-1β, and IL-6) ( 42 – 44 ). Likewise, clinical improvement of PsO with biological therapies has been associated with decreased monocyte activity ( 45 ).…”

The evaluation of cytokines to help establish diagnosis and guide treatment of autoinflammatory and autoimmune diseases

“…Our recently published case report highlights the autoinflammatory component of an autoimmune disease, that is, PsA, as well as the difficulty of selecting an appropriate therapeutic option. After several unsuccessful treatments with classical disease‐modifying anti‐rheumatic drugs (DMARDs) and biologics, the patient greatly benefited from a prospective investigation of the cytokine secretome.…”

“…Our recently published case report 91 Although IL-6 has been reported to be involved in PsA, the treatment with the biologics tocilizumab (anti-IL-6R) or clazakizumab (anti-IL-6) is not necessarily recommended. 93,94 In light of the overproduction of IL-6 by the patient's blood leukocytes, tocilizumab treatment was readily administered with a notable improvement of about 60% of her overall condition and the normalization of the inflammatory biologic parameters.…”

Risk stratification by 30-day prognostic factors of clinical outcomes after granulocyte transfusion in acute myeloid leukemia: A single-center retrospective study

“…The secretome of neutrophils is not fully understood, but the secretion of inflammatory mediators, granules, vesicles, and neutrophil extracellular traps contributes to immune function [26,27]. The role of these mediators or the measurement of their function awaits Transfusion of RBCs included filtered or non-filtered RBCs.…”