Rheumatoid Arthritis (RA): Implications in people’s loss of function

2016 ◽  
Author(s):  
Rosa Martins ◽  
Elisabete Figueiredo ◽  
Ana Andrade ◽  
Helena Moreira ◽  
Madalena Cunha
Keyword(s):  
Rheumatoid Arthritis ◽  
Loss Of Function

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

Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis

2010 ◽  
Vol 42A (4) ◽  
pp. 267-282 ◽  
Author(s):  
U. Ungethuem ◽  
T. Haeupl ◽  
H. Witt ◽  
D. Koczan ◽  
V. Krenn ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell Activation ◽  
Gene Networks ◽  
Cell Activation ◽  
Joint Disease ◽  
Disease Stage ◽  
Unknown Etiology ◽  
Coxa Vara ◽  
Molecular Signatures ◽  
Loss Of Function

Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced interpatient heterogeneity. To characterize RA at the molecular level and to uncover pathomechanisms, we performed genome-wide gene expression analysis. We identified a set of 1,054 genes significantly deregulated in pair-wise comparisons between RA and osteoarthritis (OA) patients, RA and normal donors (ND), or OA and ND. Correlation analysis revealed gene sets regulated identically in all three groups. As a prominent example secreted phosphoprotein 1 (SPP1) was identified to be significantly upregulated in RA compared with both OA and ND. SPP1 expression was found to correlate with genes expressed during an inflammatory response, T-cell activation and apoptosis, suggesting common underlying regulatory networks. A subclassification of RA patients was achieved on the basis of proteoglycan 4 (PRG4) expression, distinguishing PRG4 high and low expressors and reflecting the heterogeneity of the disease. In addition, we found that low PRG4 expression was associated with a more aggressive disease stage, which is in accordance with PRG4 loss-of-function mutations causing camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Altogether we provide evidence for molecular signatures of RA and RA subclasses, sets of new candidate genes as well as for candidate gene networks, which extend our understanding of disease mechanisms and may lead to an improved diagnosis.

Rheumatoid arthritis—clinical features

2013 ◽  
Author(s):  
Eugen Feist ◽  
Gerd-R. Burmester
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Features ◽  
Clinical Laboratory ◽  
Systemic Disease ◽  
Systemic Autoimmune Disease ◽  
Joint Involvement ◽  
Loss Of Function ◽  
Increased Risk ◽  
Autoantibody Status ◽  
Disease Entities

Rheumatoid arthritis (RA) presents with variable clinical features, making this most frequent chronic systemic autoimmune disease with characteristic joint involvement a diagnostic and therapeutic challenge. This chapter describes in detail the different clinical, laboratory and imaging findings in patients with RA. In addition to the characteristic arthritic involvement, which can lead to severe joint changes with progressive destruction and loss of function, other systemic disease manifestations as well as an increased risk for cardiovascular events and non-Hodgkin's lymphoma with relevance for patients' prognosis are described. Recent approaches to early diagnosis and stratification of patients by predictive factors for a severe course of disease are discussed. These patient profiles include increased inflammatory markers, the presence of autoantibodies, and erosive changes at the time of diagnosis. The novel classification criteria for RA and the significance of autoantibody status, namely seropositivity for antibodies against citrullinated antigens as highly specific diagnostic markers, are highlighted to further promote early differentiation of RA from other arthritic disease entities.

Anti-Inflammatory Drugs

2006 ◽  
Author(s):  
Jie Jack Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Heart Diseases ◽  
Chronic Inflammatory Disease ◽  
Medical Society ◽  
Loss Of Function ◽  
Hard Time ◽  
Back Door ◽  
Inflammatory Bowel ◽  
William Osler

Inflammation and immunity, like all other normal reactions of the body, are meant to preserve or restore health. They can nonetheless cause a range of uncomfortable symptoms. Inflammation is such a complicated process that one would have a hard time reaching a consensus on its definition. Historically, inflammation was one of the earliest recognized and defined diseases. Two thousand years ago, Roman physician and encyclopedist Aulus Cornelius Celsus (25 B.C.–50 A.D., not to be confused with Celsius, the unit for temperature) described the four cardinal signs of inflammation: calor (warmth), dolor (pain), tumor (swelling), and rubor (redness). The fifth element of inflammation, functio laesi (loss of function or movement), was noted later. Classic inflammatory diseases include rheumatoid arthritis and Crohn’s disease, an inflammatory bowel disease. However, evidence is mounting that inflammation is implicated in many diseases that are not normally considered inflammatory. For instance, when arterial plaques become inflamed they can burst open, prompting a myriad of heart diseases. Inflammatory bowel conditions greatly increase the risk of colon tumors. Even diabetes has been associated with a number of inflammatory compounds. It was hard to define what inflammation was, but finding a remedy was even more challenging. Aspirin, available in 1880, represented possibly the first really effective treatment for inflammation, whereas cortisone and other corticosteroids were not available for the treatment of rheumatoid arthritis until the early 1950s. Louis Pasteur stated, “Dans les champs de l’observation, le hazard ne favorise que les esprit préparés” [In the field of experimentation, chance favors the prepared mind]. Like numerous cases in drug discovery, Philip S. Hench’s discovery of cortisone for the treatment of rheumatoid arthritis illustrates Pasteur’s point. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by pain, swelling, and subsequent destruction of joints. Until the late 1940s, there was no viable treatment, and, understandably, pessimism prevailed in medical society about its prognosis. Even William Osler, one of the greatest physicians, said “When an arthritic patient walks in the front door, I want to run out the back door!” The situation did not change much until Hench discovered a “miracle drug” in 1949.

scholarly journals Possible Influence of Resistance to Malaria in Clinical Presentation of Rheumatoid Arthritis: Biological Significance of Natural Selection

Arthritis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Fabio Bonilla-Abadía ◽  
Gabriel J. Tobón ◽  
Carlos A. Cañas
Keyword(s):  
Rheumatoid Arthritis ◽  
Natural Selection ◽  
Chemokine Receptors ◽  
Biological Significance ◽  
Immunological Response ◽  
Immune Reactivity ◽  
Loss Of Function ◽  
Special Group ◽  
Increased Risk

Rheumatoid arthritis (RA) is a common autoimmune disease that affects all ethnic groups. Genetic factors, mainly HLA alleles, are highly associated with increased risk to develop RA. However, there are few available data about the role of these genetic polymorphisms in the prevalence or severity of RA in the Afrodescendant population, who have evolutionarily and by natural selection developed mutations that allowed them to acquire resistance to infectious diseases like malaria. Some of the mechanisms, by which this resistance was developed as a product of natural selection, are involved in different forms of immunological response, many of them of a well-known importance in the pathophysiology of RA. This paper focuses on presenting the known mechanisms of resistance to malaria and their possible contribution to the pathophysiology of RA, including “loss-of-function” mutations, lack of expression of chemokine receptors, decrease of immune complexes clearance by asplenia, or increase of immune reactivity mediated by B cells, among other mechanisms in this special group of patients.

scholarly journals The Preparation of a Novel Poly(Lactic Acid)-Based Sustained H2S Releasing Microsphere for Rheumatoid Arthritis Alleviation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 742
Author(s):  
Yue Yu ◽  
Zhou Wang ◽  
Qian Ding ◽  
Xiangbin Yu ◽  
Qinyan Yang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lactic Acid ◽  
Encapsulation Efficiency ◽  
Poly Lactic Acid ◽  
Loss Of Function ◽  
Prolonged Administration ◽  
Administration Interval ◽  
Inflammatory Autoimmune Disease

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease that mainly erodes joints and surrounding tissues, and if it is not treated in time, it can cause joint deformities and loss of function. S-propargyl-cysteine (SPRC) is an excellent endogenous hydrogen sulfide donor which can relieve the symptoms of RA through the promotion of H2S release via the CSE/H2S pathway in vivo. However, the instant release of H2S in vivo could potentially limit its further clinical use. To solve this problem, in this study, a SPRC-loaded poly(lactic acid) (PLA) microsphere (SPRC@PLA) was prepared, which could release SPRC in vitro in a sustained manner, and further promote sustained in vivo H2S release. Furthermore, its therapeutical effect on RA in rats was also studied. A spherical-like SPRC@PLA was successfully prepared with a diameter of approximately 31.61 μm, yielding rate of 50.66%, loading efficiency of 6.10% and encapsulation efficiency of 52.71%. The SPRC@PLA showed significant prolonged in vitro SPRC release, to 4 days, and additionally, an in vivo H2S release around 3 days could also be observed. In addition, a better therapeutical effect and prolonged administration interval toward RA rats was also observed in the SPRC@PLA group.

scholarly journals Functional disability is related to serum chemerin levels in rheumatoid arthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Luisa Vazquez-Villegas ◽  
Jorge I. Gamez-Nava ◽  
A. Miriam Saldaña-Cruz ◽  
Alfredo Celis ◽  
Esther N. Sanchez-Rodriguez ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Functional Disability ◽  
Cross Sectional Study ◽  
Loss Of Function ◽  
Insufficient Information ◽  
Cross Sectional ◽  
Tnf Α ◽  
Disability Group ◽  
Disabled Patients ◽  
Inflammatory Molecules

AbstractAdipokines, especially chemerin, can interact with cytokines and other molecules in inflammation. To date, there is insufficient information regarding a possible correlation between functional disability and chemerin and other pro-inflammatory molecules in rheumatoid arthritis (RA). To identify the association of functional disability with serum chemerin and other pro-inflammatory molecules, including other adipokines, cytokines and E-selectin, in patients with RA. Cross-sectional study. Assessment: disease activity (DAS28-ESR) and functional disability (HAQ-DI). We compared the adipokines (chemerin, leptin, adiponectin, resistin, and visfatin), cytokines (TNF-α, IL-6, IL-1β, and IL-18) and E-selectin levels between RA with functional disability and RA non-disabled patients. Of 82 patients with RA, 43 (52%) had functional disability. The RA with functional disability group had higher chemerin (140 vs. 112 ng/mL, p = 0.007) than the non-disabled RA group. Chemerin correlated with the HAQ-DI (rho = 0.27, p = 0.02) and DAS28-ESR (rho = 0.21, p = 0.05). Severe activity correlated with IL-6 (rho = 0.33, p = 0.003) and E-selectin (rho = 0.23, p = 0.03) but not with disability. No other pro-inflammatory molecules correlated with HAQ-DI. High chemerin levels were associated with functional disability in RA, whereas no other molecules correlated with loss of function. These results encourage further studies assessing new roles of chemerin as a marker of impairment in RA.

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