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Cytokines and regulatory T cells in rheumatoid arthritis and their relationship with response to corticoids

Author:
Paz Cazón, Banesa deUniovi authority; Alperi López, MercedesUniovi authority; Ballina García, Francisco JavierUniovi authority; Prado Cueto, CatuxaUniovi authority; Gutiérrez Martín, María del CarmenUniovi authority; Suárez Díaz, Ana MaríaUniovi authority
Subject:

Reumatología

Células T Reguladoras

Inmunología

Inmunogenética

Publication date:
2010
Publisher version:
http://dx.doi.org/10.3899/jrheum.100324
Citación:
Journal of Rheumatology, 37, p. 2502-2510 (2010); doi:10.3899/jrheum.100324
Descripción física:
p. 2502-2510
Abstract:

Objective. To analyze circulating cytokines and regulatory T cells (Treg) in patients with rheumatoid arthritis (RA) of different durations, and their association with functional interleukin 10 (IL-10) and tumor necrosis factor-α (TNF-α) genotypes in patients treated with corticosteroids. Methods. Serum levels of IL-6, IL-10, IL-17, IL-18, TNF-α, and transforming growth factor-ß (TGF-ß) were quantified in 196 patients and 61 healthy controls. Percentage of CD4+CD25high cells was determined by flow cytometry and Foxp3 expression by real-time reverse-transcription polymerase chain reaction. Data were related to clinical measurements and presence of the genotype −1082GG IL-10/−308GG TNF-α, previously associated with good response to corticosteroids. Results. Levels of TNF-α, IL-6, and IL-18 were significantly higher in patients compared to controls, while TGF-ß and IL-10 were lower. Serum samples of patients at disease onset (n = 32) had increased IL-6 and decreased TGF-ß, but there were no differences in other cytokines. These patients also presented a higher percentage of CD4+CD25high cells than those with established disease, although no significant differences were detected in Foxp3. Patients under corticosteroid treatment who were carriers of the good responder genotype had higher levels of TGF-ß, Foxp3, and Treg compared to patients with other genotypes, while relatively lower levels of TNF-α and IL-17 were observed. Conclusion. Patients at onset of RA present fewer alterations in cytokine levels and Treg than those with longer disease duration, supporting the role of disease progression in subsequent changes. The antiinflammatory balance observed in high IL-10/low TNF-α patients treated with prednisone supports the use of these genetic polymorphisms as predictors of response to corticosteroid therapy.

Objective. To analyze circulating cytokines and regulatory T cells (Treg) in patients with rheumatoid arthritis (RA) of different durations, and their association with functional interleukin 10 (IL-10) and tumor necrosis factor-α (TNF-α) genotypes in patients treated with corticosteroids. Methods. Serum levels of IL-6, IL-10, IL-17, IL-18, TNF-α, and transforming growth factor-ß (TGF-ß) were quantified in 196 patients and 61 healthy controls. Percentage of CD4+CD25high cells was determined by flow cytometry and Foxp3 expression by real-time reverse-transcription polymerase chain reaction. Data were related to clinical measurements and presence of the genotype −1082GG IL-10/−308GG TNF-α, previously associated with good response to corticosteroids. Results. Levels of TNF-α, IL-6, and IL-18 were significantly higher in patients compared to controls, while TGF-ß and IL-10 were lower. Serum samples of patients at disease onset (n = 32) had increased IL-6 and decreased TGF-ß, but there were no differences in other cytokines. These patients also presented a higher percentage of CD4+CD25high cells than those with established disease, although no significant differences were detected in Foxp3. Patients under corticosteroid treatment who were carriers of the good responder genotype had higher levels of TGF-ß, Foxp3, and Treg compared to patients with other genotypes, while relatively lower levels of TNF-α and IL-17 were observed. Conclusion. Patients at onset of RA present fewer alterations in cytokine levels and Treg than those with longer disease duration, supporting the role of disease progression in subsequent changes. The antiinflammatory balance observed in high IL-10/low TNF-α patients treated with prednisone supports the use of these genetic polymorphisms as predictors of response to corticosteroid therapy.

URI:
http://www.jrheum.org/content/early/2010/10/13/jrheum.100324
http://hdl.handle.net/10651/10185
ISSN:
0315-162X; 1499-2752
DOI:
10.3899/jrheum.100324
Patrocinado por:

Supported by grants from the Fondo de Investigación Sanitaria (Supported by grants from the Fondo de Investigación Sanitaria (FIS, PI080570) and the Fundación para el Fomento en Asturias de la Investigación Científica Aplicada y la Tecnología (FICYT, IB08-091). B. de Paz was supported by a fellowship from FICYT and C. Prado by a fellowship from FIS.) and the Fundación para el Fomento en Asturias de la Investigación Científica Aplicada y la Tecnología (FICYT, IB08-091). B. de Paz was supported by a fellowship from FICYT and C. Prado by a fellowship from FIS.

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