Date: Monday, November 6, 2017
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: NLRP3 inflammasome is an intracellular protein complex involved in the production of pro-inflammatory cytokines as IL-1β and IL-18, which has been reported to have a role in the pathogenesis of RA. Since CCH is a potent inhibitor of NLRP3, we hypothesized that it may significantly modify the expression and function of this molecular complex, reducing the inflammatory phenomenon in RA. Accordingly, the aim of this study was to evaluate the possible effect of CCH administration on the expression and activity of NLRP3 in patients with early RA.
Methods: We selected consecutive patients with RA according to the ACR/EULAR 2010 criteria with ≤12 months of evolution and were randomly assigned to 2 groups: MTX (15 mg/week); or MTX (15 mg/week) plus CCH (1.5 mg/day). Inflammasome expression by monocytes was assessed by two-color flow cytometry (CD14+NLRP3+ cells), and its function was estimated through the analysis of Caspase-1 activity (colorimetric assay). Clinical activity was assessed by HAQ-DI, CDAI, SDAI and DAS28-ESR at 0, 1 and 3 months.
Results : Twenty DMARD naive patients have been recruited, their main characteristics are shown in table 1. In a preliminary analysis of 7 patients in the MTX group and 6 patients in the MTX+CCH group after 1 month of treatment, and 3 patients in the MTX group and 4 patients in the MTX+CCH group after 3 months of treatment, all patients had increased levels of caspase-1 activity and NLRP3; patients in the MTX group had a significant change in its expression at 1 month (Table 2), however that difference was not subsequently detected at month 3. In contrast, patients in the MTX+CCH group showed a significant decrease in the expression and activity of NLRP3 at 1 and 3 months (p<0.05). Moreover, a significant improvement in clinical parameters was observed in both at months 1 and 3. We will present follow-up all patients.
Conclusion: Our preliminary data suggest that CCH administration is associated with sustained decrease in the expression and activity of the NLRP3 inflammasome. This phenomenon might contribute to decrease inflammation and may help to achieve low disease activity.
To cite this abstract in AMA style:Ramos-Bello D, Alvarez-Quiroga C, Aguilera Barragán-Pickens G, Pedro Martínez AJ, Luna-Zúñiga TA, Martínez-Flores G, Acevedo-Castañeda ES, López-Ferretis H, Cuevas-Orta E, Santillan-Guerrero E, Moreno-Valdez R, Saldaña-Baarnard M, Martinez-Martinez MU, Herrera Van Oostdam D, González-Amaro R, Abud-Mendoza C. Effect of Methotrexate (MTX), and MTX Plus Colchicine (CCH) on the Expression and Activity of NLRP3 Inflammasome in Patients with Early Rheumatoid Arthritis (RA) [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/effect-of-methotrexate-mtx-and-mtx-plus-colchicine-cch-on-the-expression-and-activity-of-nlrp3-inflammasome-in-patients-with-early-rheumatoid-arthritis-ra/. Accessed October 25, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-methotrexate-mtx-and-mtx-plus-colchicine-cch-on-the-expression-and-activity-of-nlrp3-inflammasome-in-patients-with-early-rheumatoid-arthritis-ra/