Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Methotrexate (MTX) is the most commonly used DMARD in rheumatoid arthritis (RA) patients. Since the first reports of the efficacy of low-dose MTX in RA, several studies have established its central role in the treatment of RA. Activated T CD4+ lymphocytes play a pivotal role secreting cytokines initiating and perpetuating the chronic inflammation characteristic for this disease. The role of circulating CD4+T lymphocytes in early RA is under discussion and is not well understood. The objective is evaluate the number of IFNγ, IL-4, IL-9 and IL-17 producing CD4+ T lymphocytes and in their CD4+ naïve T cells (TN), central memory (TCM), non-terminated effector memory (TNTEM) and terminated effector memory (TTEM) T cells activation/differentiation subsets in a population of recently diagnosed DMARD naïve RA patients along the first 6 months of methotrexate (MTX) treatment.
Methods: The number of IFNγ, IL-4, IL-9 and IL-17 producing CD4+ T lymphocytes, and in their TN, TCM, TNTEM and TTEMsubsets in forty untreated patients with RA before MTX treatment and at 3 and 6 months of treatment were assayed using a multiparametric flow cytometry. We have obtained peripheral blood mononuclear cells (PBMC) from AR patients. PBMC were stimulated during six hour with phorbol-myristate-acetate and ionomycin. To study the intracellular cytokine production of CD4+ T lymphocytes we used the next surface antigens: CD3, CD4, CD45RA, CD27, cells were fixed and permed, and simultaneously stained with the next intracellular cytokines: IFNγ, IL-4, IL-9 and IL-17. We acquired in a FacsAria-II flow cytometer and analyzed in Diva and Flow-Jo software. We also studied twenty-five age and sex-matched healthy subjects as controls.
Results: MTX treatment provoke a significant decrease of the IFNγ CM, NTEM and TEM effector producing T CD4 lymphocytes but not in naïve T CD4+ cells at 3 and 6 months of MTX treatment. However, the IL-17 naïve producing T CD4 lymphocytes were significant expanded along the 6 months of MTX treatment. In other hand, IL-17 CM and NTEM producing T CD4 lymphocytes were significant decreased at 6 months of MTX treatment. The intracellular expression of IL-4 and IL-9 do not shown alterations in RA naïve patients along the MTX treatment.
Conclusion: MTX treatment show immunomodulatory effects on circulating IFNγ and IL-17 producing T CD4 lymphocytes activation/differentiation stage subsets along the first 6 months of MTX treatment. Therefore, MTX are able to reduce the inflammation produce by Th1 effector T CD4 lymphocytes at 6 months. However, MTX are able to reduce Th17 in central memory but not in naive T CD4 lymphocytes, that appear increased, at 6 months of treatment.
To cite this abstract in AMA style:Monserrat Sanz J, Gómez Lahoz AM, Sosa Reina MD, Bohórquez Heras C, Movasat A, Pérez Gómez A, Ruiz Gutiérrez L, Sánchez Atrio A, Cuende Quintana E, León MJ, Diaz D, Albarrán Hernández F, Alvarez-Mon M. Metrotexate Treatment Inmunomodulate the Abnormal Cytokine Expression Present in NaïVe Rheumatoid Arthritis Patients [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/metrotexate-treatment-inmunomodulate-the-abnormal-cytokine-expression-present-in-naive-rheumatoid-arthritis-patients/. Accessed May 15, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/metrotexate-treatment-inmunomodulate-the-abnormal-cytokine-expression-present-in-naive-rheumatoid-arthritis-patients/