Influence of HLA DRB1 alleles in the susceptibility of rheumatoid arthritis and the regulation of antibodies against citrullinated proteins and rheumatoid factor

25 pages, 2 figures, 5 tables.-- Provisional PDF.[Introduction] To investigate the association between HLA-DRB1 alleles with susceptibility to rheumatoid arthritis (RA) and production of antibodies against citrullinated proteins (ACPA) and rheumatoid factor (RF).[Methods] We studied 408 patients (235 with RA, 173 non-RA) and 269 controls. ACPA, RF and HLA-DR typing were determined.[Results] We found an increased frequency of HLA DRB1 alleles with the shared epitope (SE) in ACPA-positive RA. Inversely, HLA DRB1 alleles encoding DERAA sequences were more frequent in controls than in ACPA-positive RA, and a similar trend was found for HLA DR3. However these results could not be confirmed after stratification for the presence of the SE, probably due to the relatively low number of patients. These data may suggest that the presence of these alleles may confer a protective role for ACPA-positive RA. In RA patients we observed association between SE alleles and ACPA titers in a dose-dependent effect. The presence of HLA DR3 or DERAA-encoding alleles was associated with markedly reduced ACPA levels. No association between RF titers and HLA DR3 or DERAA-encoding alleles was found.[Conclusions] HLA DRB1 alleles with the SE are associated with production of ACPA. DERAA-encoding HLA-DR alleles and HLA DR3 may be protective for ACPA-positive RA.Supported by Fundacion Mutua Madrileña PI-668 and Beca FER-Abbott 2004.Peer reviewe

Patients' and rheumatologists' preferences for the attributes of biological agents used in the treatment of rheumatic diseases in Spain

Purpose: To define importance values assigned to attributes of biological agents (BAs) by Spanish patients with rheumatic diseases (rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis) and rheumatologists. Patients and methods: This was an observational, cross-sectional design based upon a rank-based full-profile conjoint analysis. A literature review and four focus groups were undertaken to identify attributes and levels. An orthogonal matrix, combining the selected levels of attributes, was used to define scenarios. Participants ranked eight scenarios from 1 (most preferred) to 8 (least preferred). The relative importance (RI) of attributes was calculated. Multivariate regression analysis was performed to identify the characteristics that influenced the values of RI. A total of 488 patients (male 50.9%, mean age 50.6 [standard deviation {SD} 12.06] years, rheumatoid arthritis 33.8%, ankylosing spondylitis 32.4%, psoriatic arthritis 33.8%; mean time since diagnosis 12.6 [SD 8.2] years) and 136 rheumatologists (male 50.4%, mean age 46.4 [SD 9.1] years, mean time of practice 16.7 [SD 8.8] years) participated. Results: The ideal BAs for patients and physicians, respectively, should allow pain relief and improvement of functional capacity (RI 39% and 44.7%), with low risk of adverse events (RI 24.9% and 30.5%), a long time prior to perceiving the need for a new dose (RI 16.4% and 12.4%), and self-administration at home (RI 19.7% and 12.5%), as identified through their preferences. Conclusion: Although efficacy and safety are paramount for patients and rheumatologists to make a choice regarding BAs, the need for a low frequency of administration and the administration method also play a role as preference attributes for BAs

Decreased Th17 and Th1 cells in the peripheral blood of patients with early non-radiographic axial spondyloarthritis: a marker of disease activity in HLA-B27 + patients

Abstract Objective. To examine the frequency and phenotype of Th17 cells in the peripheral blood of patients with early non-radiographic axial SpA (early nrSpA). Methods. CD4 + T cells were isolated from the peripheral blood of 30 early nrSpA patients, 11 AS patients and 41 age-and sex-matched healthy controls by FicollHypaque gradient and magnetic negative selection. After polyclonal stimulation, the frequency of Th17 and Th1 cells and of cells producing TNF-a or IL-10 was determined by cytometry and concentrations of IL-17, IL-22, IFN-g, TNF-a, IL-10 and IL-4 were measured by ELISA

Early changes in biochemical markers of bone formation during teriparatide therapy correlate with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis

Summary: Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. Introduction: To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. Methods: A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. Results: PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. Conclusions: Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients

Pasados y presente. Estudios para el profesor Ricardo García Cárcel

Ricardo García Cárcel (Requena, 1948) estudió Historia en Valencia bajo el magisterio de Joan Reglà, con quien formó parte del primer profesorado de historia moderna en la Universidad Autónoma de Barcelona. En esta universidad, desde hace prácticamente cincuenta años, ha desarrollado una extraordinaria labor docente y de investigación marcada por un sagaz instinto histórico, que le ha convertido en pionero de casi todo lo que ha estudiado: las Germanías, la historia de la Cataluña moderna, la Inquisición, las culturas del Siglo de Oro, la Leyenda Negra, Felipe II, Felipe V, Austrias y Borbones, la guerra de la Independencia, la historia cultural, los mitos de la historia de España... Muy pocos tienen su capacidad para reflexionar, ordenar, analizar, conceptualizar y proponer una visión amplia y llena de matices sobre el pasado y las interpretaciones historiográficas. A su laboriosidad inimitable se añade una dedicación sin límites en el asesoramiento de alumnos e investigadores e impulsando revistas, dosieres, seminarios o publicaciones colectivas. Una mínima correspondencia a su generosidad lo constituye este volumen a manera de ineludible agradecimiento