Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Auto-inflammatory syndromes are inherited conditions characterized by recurrent inflammation (fever, abdominal pain, dermatitis, arthritis). Diagnosis and treatments are challenging as detection rate of mutations in patients with high suspicions for auto-inflammatory syndromes is low, symptoms are reminiscent of other autoimmune diseases, especially Systemic Autoimmune Rheumatic Diseases (SARD), and the cytokines abnormally secreted are unknown. As a consequence, patients can be misdiagnosed, leading to inappropriate treatment, severe complications and substantial socio-economic costs. We hypothesized that the secretion of cytokines by peripheral blood mononuclear cells (PBMC) is an indicator of the disease and could guide the treatment to the most suitable anti-cytokine.
Methods: Plasma and peripheral blood mononuclear cells (PBMCs) were obtained from healthy controls, suspected auto-inflammatory patients, and rheumatoid arthritis and systemic lupus erythematosus patients from the CHU de Québec SARD Biobank Repository Database (SBRD). PBMC were stimulated with inflammatory and immune stimuli, and cytokines in the supernatant were analyzed by multiplex assays.
Results: The cytokines found in the plasma were similar between healthy donors, SARD patients and suspected auto-inflammatory patients. In contrast, PBMC had a distinct profile of cytokine secretion. Stimulation of PBMCs with IL-15 or anti-Ig (Figure 1) led to differential secretion of members of IL-1 cytokine family, IL-12 and IFNγ in autoimmune, but not auto-inflammatory patients. In contrast, stimulation with inflammasome activators or pro-inflammatory cytokines led to selective secretion of IL-1α, IL-1β, IL-1RA, IL-18 (Figure 2), IFNγ or IL-12 in suspected auto-inflammatory patients, but not in autoimmune patients.
Conclusion: This study demonstrates that analysis of leukocytes’ secretome is reliably more sensitive than serum to reveal cytokine signatures and to predict treatment options in patients with suspected chronic auto-inflammatory syndromes.
Acknowledgement: This work was partly funded by the Fondation du Grand défi Pierre Lavoie. We thank Pfizer, Amgen, BMS, Abbvie, Roche, Sanofi-Genzyme and Merck & Co. for their unrestricted financial support of the SBRD.
Figure 1: Stimulation of PBMCs with anti-immunoglobulins to activate B cells reveals different cytokine signatures between autoimmune and auto-inflammatory patients
Figure 2: Stimulation of PBMCs with inflammasome activators or pro-inflammatory cytokines uncovers abnormal over-secretion of the IL-1 cytokine family member IL-18 by auto-inflammatory patients
To cite this abstract in AMA style:Tessier PA, Longchamps MP, Amiable N, Pagé N, Michou L, Bessette L, Fortin PR, Albert A, Chetaille AL, Pelletier M. Quantification of Leukocytes’ Secretome to Guide Diagnosis and Treatment Options in Patients with Suspected Chronic Auto-Inflammatory Syndromes [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/quantification-of-leukocytes-secretome-to-guide-diagnosis-and-treatment-options-in-patients-with-suspected-chronic-auto-inflammatory-syndromes/. Accessed August 3, 2021.
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