scholarly journals Is the disease course of rheumatoid arthritis becoming milder?: Time trends since 1985 in an inception cohort of early rheumatoid arthritis

2005 ◽  
Vol 52 (9) ◽  
pp. 2616-2624 ◽  
Author(s):  
Paco M. J. Welsing ◽  
Jaap Fransen ◽  
Piet L. C. M. van Riel
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Rheumatoid Arthritis ◽  
Time Trends ◽  
Disease Course ◽  
Inception Cohort

scholarly journals SAT0033 USING CHROMOSOME CONFORMATION FOR INSIGHT INTO PATHOGENESIS OF EARLY RHEUMATOID ARTHRITIS ENDOTYPES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 946.2-947
Author(s):  
C. Duncan ◽  
E. Hunter ◽  
C. Koutsothanasi ◽  
M. Salter ◽  
A. Akoulitchev ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Inadequate Response ◽  
Loss Of Function ◽  
Inception Cohort ◽  
Chromosome Conformation ◽  
Patient Response ◽  
Early Ra ◽  
Longitudinal Response

Background:Rheumatoid arthritis (RA) is a chronic autoimmune disease with substantial immunopathogenic heterogeneity. It is well established that early diagnosis and initiation of effective therapy is crucial to prevent loss of function. Previously, various RA treatment trajectories have been identified, however there are currently no clinically validated biomarkers that can identify these trajectories at the start of treatment. Evaluation of the structural epigenome has revealed that chromosome conformation signatures (CCS) offer great potential as binary, informative biomarkers, and have been previously shown to predict early RA patient response to Methotrexate with 90% sensitivity (1). These signatures can also reveal highly regulated areas of the genome, which may be underpinning disease endotypes.Objectives:The objective of this study was to evaluate the structural epigenome in early RA over longitudinal samples to determine whether it is associated with treatment trajectories.Methods:Patient data and samples were from the Scottish Early Rheumatoid Arthritis (SERA) cohort; a pan-Scotland inception cohort. CDAI, DAS28 ESR and DAS28 CRP measurements were calculated at baseline, 6 months and 12 months to determine longitudinal treatment response. From 3 principal longitudinal response trajectories, 18 patients (who had equivalent disease activity at baseline) were chosen to investigate the structural epigenome. These 18 comprised of responders (R), non-responders (NR) and initial responders (IR; low disease activity/remission at 6 months but moderate/high disease activity at 12 months) with 6 patients per group at each time point. 20 pooled healthy samples were used as a comparator population. EpiSwitch libraries were probed on 180K Agilent SureSelect custom arrays that were designed using EpiSwitch propriety information and publicly available data from Walshet al(2). Microarray data was analysed using the Limma package within R studio.Results:EpiSwitch array analysis showed that there were >10,000 statistically significant differential chromosomal loops between R, NR and IR. Evaluation of the 3 trajectory groups (R, NR and IR), taking into account the healthy chromosomal conformation, revealed an RA-associated structural epigenome that comprised of 10,445 chromosomal loops that were stable, over the three time points. Subsequent analysis of the distinct treatment trajectories demonstrated that 3683 of the stable, disease-associated chromosomal loops were shared by all 3. However, 4496 were associated with distinct response trajectories, with 1221, 2574 and 701 loops unique to R, NR and IR respectively.Conclusion:The stable chromosomal architecture unique to each treatment trajectory suggests that various underlying molecular endotypes may exist. Moreover, the stable loops common to all groups allude to a baseline level of dysregulation in RA and offers the potential to discover novel drivers of disease. This work provides the foundation to further our understanding of RA pathogenesis and the potential of finding a biomarker that would be of significant value in a clinical setting.References:[1] Carini, C., Hunter, E., Scottish Early Rheumatoid Arthritis Inception cohort Investigators, Ramadass, A. S., Green, J., Akoulitchev, A., et al. (2018). Chromosome conformation signatures define predictive markers of inadequate response to methotrexate in early rheumatoid arthritis.Journal of Translational Medicine,16(1), 18–11[2] Walsh, A. M., Whitaker, J. W., Huang, C. C., Cherkas, Y., Lamberth, S. L., Brodmerkel, C., et al. (2016). Integrative genomic deconvolution of rheumatoid arthritis GWAS loci into gene and cell type associations.Genome Biology,17(1), 2205Disclosure of Interests:Caitlin Duncan: None declared, Ewan Hunter: None declared, Christina Koutsothanasi: None declared, Matthew Salter: None declared, Alexandre Akoulitchev: None declared, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Carl Goodyear: None declared

scholarly journals Time Trends in Glucocorticoid Use in Rheumatoid Arthritis: Results From a Population-Based Inception Cohort, 1980-1994 Versus 1995-2007

2014 ◽  
Vol 66 (10) ◽  
pp. 1482-1488 ◽  
Author(s):  
Ashima Makol ◽  
John M. Davis ◽  
Cynthia S. Crowson ◽  
Terry M. Therneau ◽  
Sherine E. Gabriel ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Time Trends ◽  
Population Based ◽  
Inception Cohort

Treatment of Early Rheumatoid Arthritis in a Multinational Inception Cohort of Latin American Patients

2012 ◽  
Vol 18 (7) ◽  
pp. 327-335 ◽  
Author(s):  
Mario H. Cardiel ◽  
Bernardo A. Pons-Estel ◽  
Mónica P. Sacnun ◽  
Daniel Wojdyla ◽  
Verónica Saurit ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Latin American ◽  
Early Rheumatoid Arthritis ◽  
Inception Cohort

scholarly journals Antibodies against citrullinated peptides are associated with clinical and radiological outcomes in patients with early rheumatoid arthritis: a prospective longitudinal inception cohort study

RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e000946 ◽  
Author(s):  
Antonia Boman ◽  
Mikael Brink ◽  
Anders Lundquist ◽  
Monica Hansson ◽  
Linda Mathsson-Alm ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Rheumatoid Arthritis ◽  
Tyrosine Phosphatase ◽  
Area Under The Curve ◽  
Inception Cohort ◽  
Radiological Progression ◽  
Prospective Longitudinal Study ◽  
Larsen Score ◽  
Custom Made ◽  
Prospective Longitudinal

IntroductionAnticitrullinated peptide antibody (ACPA) responses for 22 citrullinated peptides in patients with early rheumatoid arthritis (RA) were analysed and related to radiological and clinical outcome during the first 2 years in a prospective inception cohort.MethodsThe ACPA reactivities were assessed in 1022 patients with early RA (symptoms <12 months) using the custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden) in a prospective longitudinal study of observational assessments of Disease Activity Score (DAS28 and its components) and radiology during the first 24 months, accounting for the treatment.ResultsFrequency of ACPA reactivities varied between 13.3% and 63.1%. Of the anticyclic citrullinated peptide-2 (anti-CCP2) antibody-negative patients, ACPA reactivities were positive in 32.6%. Smoking, human leucocyte antigen-shared epitope (HLA-SE), anti-CCP2/rheumatoid factor, protein tyrosine phosphatase non-receptor type 22 (1858C/T) and DAS28 were significantly associated with number of ACPA reactivities. The ACPA reactivities modified differently the development of DAS28 over 24 months (identified using trajectories). Anti-Filaggrin307-324, anti-hnRNP (Peptide)-Z1 and anti-F4-CIT-R antibodies anticipated lower DAS28 values (p<0.01–0.05), while positivity for anti-Fibrinogen(Fib)β62-78(74), and anti-Fibα563-583 predicted higher DAS28 (p<0.01 both). Interaction between anti-Fibß36-52, anti-Pept-5 and anti-Bla-26 antibodies, respectively, and DAS28 during 24 months decreased significantly the DAS28 values (p<0.01–0.05). Corticosteroids and biologicals were related to DAS28-area under the curve and Larsen score 24 months. Anti-vimentin2-17 antibodies remained significantly associated with Larsen score at baseline and 24 months, respectively, and radiological progression, besides biologicals at 24 months adjusted for sex and age.ConclusionsSeveral ACPA reactivities modified significantly the DAS28 development during the first 24 months and were significantly associated with Larsen score at baseline, 24 months and radiological progression.

HLA-G may predict the disease course in patients with early rheumatoid arthritis

2013 ◽  
Vol 74 (4) ◽  
pp. 425-432 ◽  
Author(s):  
Roberta Rizzo ◽  
Ilaria Farina ◽  
Daria Bortolotti ◽  
Elisa Galuppi ◽  
Antonella Rotola ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Rheumatoid Arthritis ◽  
Disease Course
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