Hospital Universitario Of La Princesa Iis Princesa

Madrid, Spain

Hospital Universitario Of La Princesa Iis Princesa

Madrid, Spain
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Lopez-Santalla M.,CSIC - National Center for Biotechnology | Salvador-Bernaldez M.,CSIC - National Center for Biotechnology | Gonzalez-Alvaro I.,Hospital Universitario Of La Princesa Iis Princesa | Castaneda S.,Hospital Universitario Of La Princesa Iis Princesa | And 7 more authors.
Arthritis and Rheumatism | Year: 2011

Objective The p38 MAPK is important in the pathogenic immune response in rheumatoid arthritis (RA). The p38 molecule can be activated through phosphorylation on Thr180-Tyr182 by upstream MAPK kinases and via an alternative pathway through phosphorylation on Tyr323. We undertook this study to quantify the phosphorylation of Tyr323 p38 and of Thr180-Tyr182 p38 on T cells from healthy controls and patients with RA or ankylosing spondylitis (AS) to identify variables associated with p38 phosphorylation and disease activity. Methods We measured p38 phosphorylation on Tyr323 and Thr180-Tyr182 by flow cytometry and Western blotting on T cells from 30 control subjects, 33 AS patients, 30 patients with RA in remission, and 79 patients with active RA. We collected the clinical characteristics and analyzed correlations between clinical variables, the Disease Activity Score in 28 joints (DAS28), and p38 phosphorylation levels. Multivariate regression analysis was performed to identify variables associated with p38 phosphorylation on Tyr323 and Thr180-Tyr182. Results Phosphorylation of p38 on Tyr 323 was higher in T cells from patients with active RA (P = 0.008 versus healthy controls) than in patients with RA in remission or in patients with AS. Tyr323 p38 phosphorylation was associated with disease activity determined by the DAS28 (P = 0.017). Enhanced p38 phosphorylation was linked to Lck-mediated activation of the Tyr323-dependent pathway in the absence of upstream MAPKK activation. Conclusion Our results indicate that phosphorylation status on Tyr323 p38 correlates with RA disease activity and suggest that the Tyr323-dependent pathway is an attractive target for down-regulation of p38 activity in RA patients. Copyright © 2011 by the American College of Rheumatology.


Gonzalez-Alvaro I.,Hospital Universitario Of La Princesa Iis Princesa | Ortiz A.M.,Hospital Universitario Of La Princesa Iis Princesa | Alvaro-Gracia J.M.,Hospital Universitario Of La Princesa Iis Princesa | Castaneda S.,Hospital Universitario Of La Princesa Iis Princesa | And 10 more authors.
PLoS ONE | Year: 2011

Background: Interleukin-15 (IL-15) is thought to be involved in the physiopathological mechanisms of RA and it can be detected in the serum and the synovial fluid of inflamed joints in patients with RA but not in patients with osteoarthritis or other inflammatory joint diseases. Therefore, the objective of this work is to analyse whether serum IL-15 (sIL-15) levels serve as a biomarker of disease severity in patients with early arthritis (EA). Methodology and Results: Data from 190 patients in an EA register were analysed (77.2% female; median age 53 years; 6-month median disease duration at entry). Clinical and treatment information was recorded systematically, especially the prescription of disease modifying anti-rheumatic drugs. Two multivariate longitudinal analyses were performed with different dependent variables: 1) DAS28 and 2) a variable reflecting intensive treatment. Both included sIL-15 as predictive variable and other variables associated with disease severity, including rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). Of the 171 patients (638 visits analysed) completing the follow-up, 71% suffered rheumatoid arthritis and 29% were considered as undifferentiated arthritis. Elevated sIL-15 was detected in 29% of this population and this biomarker did not overlap extensively with RF or ACPA. High sIL-15 levels (β Coefficient [95% confidence interval]: 0.12 [0.06-0.18]; p&0.001) or ACPA (0.34 [0.01-0.67]; p = 0.044) were significantly and independently associated with a higher DAS28 during follow-up, after adjusting for confounding variables such as gender, age and treatment. In addition, those patients with elevated sIL-15 had a significantly higher risk of receiving intensive treatment (RR 1.78, 95% confidence interval 1.18-2.7; p = 0.007). Conclusions: Patients with EA displaying high baseline sIL-15 suffered a more severe disease and received more intensive treatment. Thus, sIL-15 may be a biomarker for patients that are candidates for early and more intensive treatment. © 2011 González-Álvaro et al.

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