Rheumatoid Arthritis: Gonzalez-Alvaro I

Castrejón I, Ortiz AM, García-Vicuña R, Lopez-Bote JP, Humbría A, Carmona L, Gonzalez-Alvaro I. · Rheumatology Service, Hospital Universitario de la Princesa, Madrid, Spain. · Clin Exp Rheumatol. · Pubmed #19032807 No free full text.

Abstract: A formula for calculating disease activity score with 28 joint counts (DAS28) with C-reactive protein (CRP) instead of the erythrocyte sedimentation rate (ESR) has been proposed. OBJECTIVE: Here we analyze the factors that contribute to the differences in the DAS28 when calculated using either the ESR (DAS28-ESR) or the CRP values (DAS28-CRP). METHODS: We analyzed the data from 587 visits made by 220 patients with early arthritis. The age at the onset of the disease was 51+/-16 years old and 76.3% of the patients were women. The disease evolution at the first visit was 5 months and at each visit information related to several variables was collected, including that necessary to calculate the DAS28-ESR and DAS28-CRP. We defined a new variable DIFDAS=DAS28-ESR-DAS28-CRP to analyze which independent variables account for differences between the two indexes. RESULTS: There was a correlation between the two indexes of 0.91 (p<0.0001), although the DAS28-ESR value obtained was higher than that of DAS28-CRP at approximately 90% of the visits. Significantly, the difference between both indexes was higher than 0.6 in 44% of the visits studied. A multivariate analysis showed that female gender and disease duration were associated with the higher values obtained for DAS28-ESR when compared to those of DAS28-CRP. CONCLUSION: Our data show that DAS28-ESR and DAS28-CRP are not fully equivalent, because the former usually produces higher values. This finding is particularly relevant in females and patients with a long disease duration.

Dieguez-Gonzalez R, Akar S, Calaza M, Perez-Pampin E, Costas J, Torres M, Vicario JL, Velloso ML, Navarro F, Narvaez J, Joven B, Herrero-Beaumont G, Gonzalez-Alvaro I, Fernandez-Gutierrez B, de la Serna AR, Carreño L, Lopez-Longo J, Caliz R, Collado-Escobar MD, Blanco FJ, Fernandez-Lopez C, Balsa A, Pascual-Salcedo D, Gomez-Reino JJ, Gonzalez A. · Laboratorio de Investigacion 2 and Rheumatology Unit, Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain. · Ann Rheum Dis. · Pubmed #18434448 No free full text.

Abstract: OBJECTIVE: To examine genetic association between rheumatoid arthritis (RA) and known polymorphisms in core genes of the nuclear factor (NF)kappaB pathway, the major intracellular pathway in RA pathogenesis. METHODS: Discovery and replication sample sets of Spanish patients with RA and controls were studied. A total of 181 single nucleotide polymorphisms (SNPs) uniformly spaced along the genomic sequences of 17 core genes of the NFkappaB pathway (REL, RELA, RELB, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, IKBKA, IKBKB, IKBKE, IKBKAP, KBRAS1, KBRAS2, MAP3K1, MAP3K14, TAX1BP1) were studied by mass spectrometry analysis complemented with 5'-nuclease fluorescence assays in the discovery set, 458 patients with RA and 657 controls. SNPs showing nominal significant differences were further investigated in the replication set of 1189 patients with RA and 1092 controls. RESULTS: No clear reproducible association was found, although 12 SNPs in IKBKB, IKBKE and REL genes showed significant association in the discovery set. Interestingly, two of the SNPs in the IKBKE gene, weakly associated in the discovery phase, showed a trend to significant association in the replication phase. Pooling both sample sets together, the association with these two SNPs was significant. CONCLUSION: We did not find any major effect among the explored members of the NFkappaB pathway in RA susceptibility. However, it is possible that variation in the IKBKE gene could have a small effect that requires replication in additional studies.

Gonzalez-Alvaro I, Ortiz AM, Garcia-Vicuña R, Balsa A, Pascual-Salcedo D, Laffon A. · Rheumatology Department, Hospital Universitario de La Princesa, Madrid, Spain. · Clin Exp Rheumatol. · Pubmed #14611115 No free full text.

Abstract: OBJECTIVE: To study the serum levels of IL-15 in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), seronegative spondyloarthropathies (SSd) and healthy donors. METHODS: The IL-15 serum levels were measured by ELISA in sera from 50 RA patients, 30 patients with SLE, 30 patients with SSd and 30 healthy donors. In RA patients, several clinical and demographic parameters were also obtained at the time of sample collection. IL-15 levels were compared in different RA subpopulations (positive or negative rheumatoid factor [RF], long term or recent onset disease, high or low disease activity). In addition, the possible association with other demographic and clinical parameters (gender, age, disease duration, etc) was also analysed. RESULTS: RA patients had significantly higher serum levels of IL-15 (102.4 +/- 150 pg/ml; p = 0.0001) than SLE patients (9.8 +/- 15.3 pg/ml), SSd patients (7.9 +/- 14.6 pg/ml) and healthy donors' (5.2 +/- 11.6 pg/ml). RA patients with a disease evolution less than 2 years showed lower IL-15 levels (33.7 +/- 62.2 pg/ml) than those with long-term disease (152.4 +/- 64.6 pg/ml; p = 0.004). In addition, a significant correlation between IL15 in serum and the number of disease-modifying antirheumatic drugs (DMARDs) prescribed was detected in RA patients (r = 0.42; p = 0.002). No association between IL-15 levels and age, gender, RF or disease activity was observed in this group. CONCLUSION: IL-15 is elevated in RA patients, specially in those with long term disease, compared to other rheumatic disorders. This finding supports that IL-15 is involved in the perpetuation of RA synovitis.

Gonzalez-Alvaro I, Carmona L, Balsa A, Sanmarti R, Belmonte MA, Tena X, Anonymous00148. · Department of Rheumatology, Hospital Universitario de la Princesa, Madrid, Spain. · J Rheumatol. · Pubmed #12672186 No free full text.

Abstract: OBJECTIVE: To determine the adequacy of disease modifying antirheumatic drug (DMARD) prescription to disease activity in patients with rheumatoid arthritis (RA) and to assess whether the reasons for DMARD discontinuation agree with published evidence. METHODS: Cross-sectional analysis of the baseline year of a RA cohort (n = 788) randomly selected from the clinical registries of 34 centers. Data about current and previous DMARD use was collected from medical records and confirmed by the patient. Disease activity score (DAS), Health Assessment Questionnaire (HAQ) and Larsen scores, and other clinical data were obtained during the study visit. RESULTS: At baseline visit, 607 patients (77%) were receiving one or more DMARD. Mean DAS, HAQ, and Larsen scores (+/- SD) were: 3.40 +/- 1.22, 1.6 +/- 0.4, and 54.68 +/- 26.37, respectively. Methotrexate (MTX) was the most frequently prescribed DMARD and parenteral gold salts (GS) showed the highest rate of discontinuation. MTX was used as single therapy in a significantly higher proportion (64.3%) than other DMARD (< 50%) and treatment discontinuation due to inefficacy was significantly less frequent (25.5%) than with other DMARD (> 40%). However, the DAS28 was significantly worse in the group treated with MTX in single therapy than in the group treated with GS alone (4.13 vs 3.43; p = 0.032). CONCLUSION: Despite the high use of DMARD among Spanish patients with RA, a significant number of them still have poor control of the disease. In addition, our data show a different perception of ineffectiveness depending on the DMARD used. A non-systematic use of objective quantitative tools for assessment of RA activity and some non-evidence based decisions on the management of DMARD may account for these findings.

Ortiz AM, Laffon A, Gonzalez-Alvaro I. · Rheumatology Department, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Spain. · Rheumatol Int. · Pubmed #11958434 No free full text.

Abstract: OBJECTIVE: The aim was to study a possible relationship between CD69 expression on lymphocytes and interleukin-15 (IL-15) levels in synovial fluid (SF) from patients with different inflammatory arthropathies. METHODS: CD69 expression was assessed by two-color flow cytometry on different subsets of synovial fluid lymphocytes (SFL) obtained from patients with diagnoses of rheumatoid arthritis (RA), seronegative spondyloarthropathy (SSd), and crystal-associated arthritis (CAA). The IL-15 levels in synovial fluid supernatants were measured by enzyme-linked immunoassay (ELISA). RESULTS: No significant differences between the three groups of arthropathies were observed in the distribution of synovial fluid lymphocyte subsets. CD69-positive SFL were mainly CD3-, CD45RO-, and CCR5-positive cells. Although no significant differences in the percentage of CD69-positive lymphocytes were observed between the three groups of patients, the highest level of CD69 expression on lymphocytes was observed in RA patients (mean fluorescence intensity 37.9 +/- 5.2 compared to 17.5 +/- 3.3 in SSd and 12.4 +/- 2.6 in CAA, P = 0.007 and P < 0.001, respectively). In addition, the expression of CD69 on SFL from RA correlated with their respective IL-15 levels measured in SF supernatants. CONCLUSION: Our data provide in vivo evidence of the putative role that IL-15 can play in the high expression of CD69 on SFL from RA patients.

Sanmartí R, Gómez-Casanovas E, Solé M, Cañete J, Gratacós J, Carmona L, Gonzalez-Alvaro I, Muñoz-Gómez J. · No affiliation provided · J Rheumatol. · Pubmed #15124276 links to  free full text

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