99 research outputs found
Improved RA classification among early arthritis patients with the concordant presence of three RA autoantibodies: Analysis in two early arthritis clinics
Background: The patients with RA benefit from early identification soon after the first clinical symptoms appear.
The 2010 ACR/EULAR classification criteria were developed to fulfill this need and their application has been
demonstrated to be effective. However, there is still room for improvement. Therefore, we aimed to evaluate the
potential of the concordant presence of RF, anti-CCP and anti-carbamylated protein antibodies to improve current
RA classification among early arthritis (EA) patients.
Methods: Data from the first visit of 1057 patients in two EA prospective cohorts were used. The serological scores
from the 2010 ACR/EULAR criteria and the concordant presence of the three RA autoantibodies were assessed
relative to a gold standard consisting of the RA classification with the 1987 ACR criteria at the 2 years of follow-up.
Results: The concordant presence of three antibodies showed predictive characteristics allowing for direct
classification as RA (positive predictive value = 96.1% and OR = 80.9). They were significantly better than the
corresponding to the high antibody titers defined as in the 2010 classification criteria (PPV = 88.8%, OR = 26.1). In
addition, the concordant presence of two antibodies was also very informative (PPV = 82.3%, OR = 15.1). These
results allowed devising a scoring system based only on antibody concordance that displayed similar overall
performance as the serological scoring system of the 2010 criteria. However, the best classification was obtained
combining the concordance and 2010 serological systems, a combination with a significant contribution from each
of the two systems.
Discussion: The concordant presence of RA autoantibodies showed an independent contribution to the
classification of EA patients that permitted increased discrimination and precision.This work was supported by the Instituto de Salud Carlos III (Spain) through
grants [PI17/01606 and RD16/0012/0014 to AG; RD16/0012/0011 to IG-A and
RD16/0012/0012 to AB]. These grants are partially financed by the European
Regional Development Fund of the EU (FEDER). CR was supported by Ministerio
de Educacion Cultura y Deporte (Spain) through a FPU pre-doctoral fellowship
[FPU15/03434]. LR-M was supported by a Xunta de Galicia
predoctoral contract
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
The immunogenicity to the first anti-TNF therapy determines the outcome of switching to a second anti-TNF therapy in spondyloarthritis patients
Introduction: Anti-TNF drugs have proven to be effective against spondyloarthritis (SpA), although 30% of patients
fail to respond or experience adverse events leading to treatment discontinuation. In rheumatoid arthritis, the
presence of anti-drug antibodies (ADA) against the first TNF inhibitor influences the outcome after switching. Our
aim was to assess whether the response to a second anti-TNF drug is related to the previous development of ADA
to the first anti-TNF drug SpA patients.
Methods: Forty-two SpA patients began a second anti-TNF drug after failing to respond to the first anti-TNF
therapy. Clinical activity was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline (at
the beginning of the first and second anti-TNF therapy) and at 6 months after switching. The drug and ADA levels
were measured by ELISA before each administration.
Results: All patients were treated with anti-TNF drugs and mainly due to inefficacy were switched to a second
anti-TNF drug. Eleven of 42 (26.2%) developed ADA during the first biologic treatment. At baseline, no differences
in ASDAS were found in patients with or without ADA to the first anti-TNF drug (3.52 ± 1.03 without ADA vs. 3.14
± 0.95 with ADA, p = 0.399) and to the second anti-TNF drug (3.36 ± 0.94 without ADA vs. 3.09 ± 0.91 with ADA, p
= 0.466). At 6 months after switching, patients with previous ADA had lower disease activity (1.62 ± 0.93 with ADA
vs. 2.79 ± 1.01 without ADA, p = 0.002) and most patients without ADA had high disease activity state by the
ASDAS (25 out of 31 (80.6%) without ADA vs. 3 out of 11 (27.3%) with ADA, p = 0.002).
Conclusions: In SpA the failure to respond to the first anti-TNF drug due to the presence of ADA predicts a better
clinical response to a second anti-TNF drug
Association of CD247 polymorphisms with rheumatoid arthritis: a replication study and a meta-analysis
Given the role of CD247 in the response of the T cells, its entailment in autoimmune diseases and in order to better clarify the role of this gene in RA susceptibility, we aimed to analyze CD247 gene variants previously associated with other autoimmune diseases (rs1052237, rs2056626 and rs864537) in a large independent European Caucasian population. However, no evidence of association was found for the analyzed CD247 single-nucleotide polymorphisms (SNPs) with RA and with the presence/absence of anti-cyclic citrullinated polypeptide. We performed a meta-analysis including previously published GWAS data from the rs864537 variant, revealing an overall genome-wide significant association between this CD247 SNP and RA with anti-CCP (ORâ=â0.90, CI 95%â=â0.87-0.93, Poverallâ=â2.1Ă10â10). Our results show for first time a GWAS-level association between this CD247 polymorphism and RA risk
Translation and cross-cultural adaptation of the mSQUASH into Spanish
Background: There is a lack of outcome measures for the assessment of physical activity in patients with axial spondyloarthritis (axSpA). For this matter, the modified Short QUestionnaire to Assess Health (mSQUASH) was developed and validated, originally in Dutch. Objective: To translate and cross-culturally adapt the mSQUASH into Spanish and to evaluate the equivalence of the translated version in patients with axSpA. Methods: The mSQUASH was translated following forward-backward procedure according to the protocol of Beaton. Two bi-lingual translators produced independent forward translations of the mSQUASH into Spanish, and the versions were harmonized in a consensual version. Another translator back translated the synthesized version into Dutch. A scientific committee reached consensus on discrepancies and developed a pre-final version of the questionnaire. The field test with cognitive debriefing involved 10 patients with axSpA with different gender, age, disease duration, educational level and working status. Results: The translation process of the mSQUASH was completed without major issues. The first translation needed several iterations due to small discrepancies in the wording. Back-translation was performed without difficulties, and the scientific committee agreed upon a final version of the questionnaire. Cognitive debriefing showed the Spanish questionnaire to be clear, relevant, understandable and comprehensive. The preliminary version was accepted with minor modifications. Conclusions: The resulting Spanish version of the mSQUASH showed good linguistic and face validity according to the field test, revealing potential for use in clinical practice and research. In order to conclude the cross-cultural adaptation of the mSQUASH into Spanish, the next step is the assessment of psychometric properties of the Spanish version.</p
The TT Genotype of the STAT4 rs7574865 Polymorphism Is Associated with High Disease Activity and Disability in Patients with Early Arthritis
[Background]
The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis.
[Methodology and Results]
We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5âČ allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (ÎČ coefficient [95% confidence interval] = 0.42 [0.01â0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = â0.27 [â0.56â â0.01], p = 0.042; TT genotype = â0.68 [â1.64â â0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype.
[Conclusions]
Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.This work was partially supported by the RETICS (Redes Tematicas de InvestigaciĂłn Cooperativa, Cooperative Research Thematic Networks) Program, RD08/0075 (RIER) and FIS (Fondo de InvestigaciĂłn en Salud) Health Research Fund grant FIS 08/0754 to IG-A from Instituto de Salud Carlos III (ISCIII; www.isciii.es) and by grants from the European Innovative Medicines Initiative and BTCure Program (http://www.life-sciences-europe.com/orgaânisation/btcure-project-imi-efpia-201103â-innovative-medicines-initiative-2001-28â657.html). The work of IG-A was in part supported by a Research Intensification Grant from the National Health Care System (Instituto Carlos III; www.isciii.es), Madrid, Spain
Translation and cross-cultural adaptation of the mSQUASH into Spanish
Background: There is a lack of outcome measures for the assessment of physical activity in patients with axial spondyloarthritis (axSpA). For this matter, the modified Short QUestionnaire to Assess Health (mSQUASH) was developed and validated, originally in Dutch. Objective: To translate and cross-culturally adapt the mSQUASH into Spanish and to evaluate the equivalence of the translated version in patients with axSpA. Methods: The mSQUASH was translated following forward-backward procedure according to the protocol of Beaton. Two bi-lingual translators produced independent forward translations of the mSQUASH into Spanish, and the versions were harmonized in a consensual version. Another translator back translated the synthesized version into Dutch. A scientific committee reached consensus on discrepancies and developed a pre-final version of the questionnaire. The field test with cognitive debriefing involved 10 patients with axSpA with different gender, age, disease duration, educational level and working status. Results: The translation process of the mSQUASH was completed without major issues. The first translation needed several iterations due to small discrepancies in the wording. Back-translation was performed without difficulties, and the scientific committee agreed upon a final version of the questionnaire. Cognitive debriefing showed the Spanish questionnaire to be clear, relevant, understandable and comprehensive. The preliminary version was accepted with minor modifications. Conclusions: The resulting Spanish version of the mSQUASH showed good linguistic and face validity according to the field test, revealing potential for use in clinical practice and research. In order to conclude the cross-cultural adaptation of the mSQUASH into Spanish, the next step is the assessment of psychometric properties of the Spanish version.</p
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