Date: Sunday, November 13, 2016
Session Title: Muscle Biology, Myositis and Myopathies
Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Idiopathic inflammatory myopathies (IIM) are a group of rare, heterogeneous autoimmune diseases of unknown etiology. Different physiopathogenic mechanisms have been proposed, including the production of autoantibodies and pathogenic cytokines. Ro52/TRIM21 is a ubiquitin ligase, and antibodies against this molecule have been described in different autoimmune diseases, including IIM. The aim of this study was to assess if there is a differential production of cytokines, associated with Ro52/TRIM 21 levels, in patients with recent-onset IIM.
Methods: We included patients within the first month of IIM diagnosis according to Bohan and Peter’s criteria. They all had active disease, had no treatment, and were seen at a tertiary care center between 2013 and 2015. Patients with diagnosis of dermatomyositis (DM), polymyositis and antisynthetase syndrome, as well as age and gender-matched healthy donors were recruited. PBMCs were isolated by Ficoll-Hypaque. CD4+ T cells and monocytes (CD14+) were purified by magnetic selection. Effector T cells were stimulated with PMA plus ionomycin and monocytes with LPS. Supernatants were collected and cytokine levels were measured. Levels of IFN-α were determined by ELISA, and the other cytokines were assessed by cytometric bead array. The expression of TRIM21 in different PBMC subsets was evaluated by Western Blot.
Results: We included 15 patients with IIM and 15 healthy controls. DM was the most prevalent IIM (73.3%). Most patients were female (66%), with a mean age of 43 ± 15 years. After stimulation, T cells from IIM patients had a higher production of IL-17 (80.22 ± 28.57 vs 14.7 ± 5.47, p=0.017) and TNF-α (2325.1 ± 405.14 vs 1055.62 ± 235.21, p=0.005) than healthy controls. After being stimulated with LPS, monocytes from IIM patients produced more IL-6 (8441.2 ± 1801.03 vs 1996.6 ± 650.58, p=0.003) and IFN-α (85.27 ± 13.78 vs 13.3 ± 0.87, p=0.002) than control monocytes. Also, patients with IIM showed a decreased protein expression of TRIM21 in comparison to healthy controls in different PBMC subsets: total PBMC (0.971 ± 0.603 vs 1.849 ± 0.927 p=0.016), CD4+ lymphocytes (0.797 ± 0.54 vs 2.413 ±0.786, p=0.017), and monocytes (0.875 ± 0.358 vs1.89 ±0.209, p<0.001).
Conclusion: Our findings suggest that patients with IIM are characterized by a higher production of proinflammatory cytokines, associated with decreased levels of TRIM21. The deficiency in TRIM21 could potentially lead to decreased IRF ubiquitination and degradation, enhancing type-1 IFN signaling. Along with the higher IFN-α production, this could contribute to the IFN signature found in IIM patients. Also, the specific cytokine profile could represent a potential biomarker for IIM, particularly DM patients.
To cite this abstract in AMA style:Barrera-Vargas A, Galindo-Feria AS, Gómez-Martín D, Merayo-Chalico J, Alcocer-Varela J. Pro-Inflammatory Cytokines Produced By Different Subsets of Peripheral Blood Mononuclear Cells Are Associated with Ro52/TRIM21 Deficiency in Patients with Inflammatory Myopathies [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/pro-inflammatory-cytokines-produced-by-different-subsets-of-peripheral-blood-mononuclear-cells-are-associated-with-ro52trim21-deficiency-in-patients-with-inflammatory-myopathies/. Accessed June 1, 2023.
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