Session Type: Poster Session A
Session Time: 8:30AM-10:30AM
Background/Purpose: NAD+ is a key cofactor and second messenger for multiple cellular processes that exhibits antioxidant, anti-apoptotic, and anti-inflammatory properties. Numerous publications and clinical trials have shown the beneficial effects of NAD+ boosters in different diseases. However, to date no studies have evaluated the NAD+ metabolism and the therapeutic effects of NAD+ boosters in RA patients.
Aims: 1- To study the NAD+ metabolism in RA patients and its association with key clinical features; 2-To evaluate the effect of anti-TNF therapy in the NAD+ metabolism; 3- To analyze the beneficial effects of NAD+ boosters in leukocytes from active RA patients.
Methods: Plasma and PBMCs were purified from 100 RA patients and 50 healthy donors (HDs). NAD+ levels were determined by using the NAD/NADH-Glo Assay. Gene expression analysis of markers related to the synthesis (NAMPT, NMNAT2, NRK1), transport (Cx43) and consumption of NAD+ (PARP-1, Sirtuin-1, CD157, CD38 y CD73) were performed in PBMCs by RT-PCR.
Moreover, in a second cohort of 50 RA patients treated with anti-TNF therapy, changes in the levels of NAD+ were analyzed before and after 6 months of treatment.
In parallel, PBMCs from a third cohort of 10 active RA patients were treated ex vivo with 1 mM of NAD+ boosters including nicotinamide (NAM), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN). After 24 hours, intracellular reactive oxygen species (ROS) levels and the % of apoptotic PBMCs were assessed by flow cytometry. Finally, a panel of key pro-inflammatory genes was evaluated by RT-PCR.
Results: NAD+ levels were significantly reduced in plasma of RA patients compared with HDs, and directly related to disease activity. Accordingly, the expression levels of genes involved in the consumption of NAD+ such as SIRT-1, CD38 and PARP-1 were found up-regulated in PBMCs from RA patients. The levels of NAMPT and Cx43 were found increased suggesting a compensatory response of the organism against the depletion of NAD+ levels. The altered metabolism of NAD+ was associated with the increased expression of several cytokines such as TNF, IL6, IL1, IL8 and CCL2 highlighting the role of inflammation in the altered NAD+ metabolism.
Anti-TNF therapy restored the altered NAD+ levels towards those showed by HDs. Furthermore, the clinical response promoted by anti-TNF therapy correlated with changes in NAD+ levels.
In vitro treatments of PBMCs isolated from active RA patients with NAD+ boosters significantly increased the NAD+ levels and promoted a deep reduction of intracellular ROS levels, the percentage of apoptotic cells and the expression levels of key inflammatory mediators, such as IL-6, IL-8, IL-1b, TNF-α, CCL2, IL-23, and STAT-3.
Conclusion: 1. NAD+ metabolism is altered and associated with the disease activity and the pro-inflammatory status of RA patients. 2. Anti-TNF therapy restored NAD+ levels, which was directly linked to the clinical effectiveness. 3. NAD+ boosters reduced the oxidative, apoptotic, and inflammatory profile of RA leukocytes through the parallel increase of intracellular NAD+ levels. Thus, NAD+ boosters might be considered novel therapeutic tools for RA patients.
Supported by: FIS18/0837,RTI2018-100695-B-I00,P18-RT-4264,CVI276
To cite this abstract in AMA style:Pérez-Sánchez C, Sanchez-Mendoza L, Barbarroja N, Abalos-Aguilera M, Luque-Tevar M, Patiño-Trives A, Arias de la Rosa I, Román-Rodriguez C, Moreno J, Buron M, Gonzalez-Reyes J, Rojas-Gimenez M, Collantes-Estevez E, Escudero a, Villalba J, lopez-pedrera C. The NAD+ Metabolism Is Altered in Rheumatoid Arthritis and Its Modulation with NAD+ Boosters Exhibits Key Anti-Inflammatory and Anti-Oxidant Effects [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/the-nad-metabolism-is-altered-in-rheumatoid-arthritis-and-its-modulation-with-nad-boosters-exhibits-key-anti-inflammatory-and-anti-oxidant-effects/. Accessed January 30, 2023.
« Back to ACR Convergence 2021
ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-nad-metabolism-is-altered-in-rheumatoid-arthritis-and-its-modulation-with-nad-boosters-exhibits-key-anti-inflammatory-and-anti-oxidant-effects/