scholarly journals A Cross-Sectional and Longitudinal Study to Define Alarmins and A-SAA Variants as Companion Markers in Early Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Federica Ciregia ◽  
Gwenaël Nys ◽  
Gaël Cobraiville ◽  
Valérie Badot ◽  
Silvana Di Romana ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Functional Disability ◽  
Joint Damage ◽  
Response To Therapy ◽  
Biologic Treatment ◽  
Cross Sectional ◽  
Amyloid A ◽  
Dmard Treatment ◽  
Biologic Dmard

Nowadays, in the study of rheumatoid arthritis (RA), more and more interest is directed towards an earlier effective therapeutic intervention and the determination of companion markers for predicting response to therapy with the goal to prevent progressive joint damage, deformities, and functional disability. With the present work, we aimed at quantifying in a cohort of early RA (ERA) patients naïve to DMARD therapy, proteins whose increase was previously found associated with RA: serum amyloid A (A-SAA) and alarmins. Five A-SAA variants (SAA1α, SAA1β, SAA1γ, SAA2α, and SAA2β) but also S100A8 and S100A9 proteins were simultaneously quantified in plasma applying a method based on single targeted bottom-up proteomics LC-MS/MS. First, we compared their expression between ERA (n = 100) and healthy subjects (n = 100), then we focused on their trend by monitoring ERA patients naïve to DMARD treatment, 1 year after starting therapy. Only SAA1α and SAA2α levels were increased in ERA patients, and SAA2α appears to mostly mediate the pathological role of A-SAA. Levels of these variants, together with SAA1β, only decreased under biologic DMARD treatment but not under methotrexate monotherapy. This study highlights the importance to better understand the modulation of expression of these variants in ERA in order to subsequently better characterize their biological function. On the other hand, alarmin expression increased in ERA compared to controls but remained elevated after 12 months of methotrexate or biologic treatment. The work overcomes the concept of considering these proteins as biomarkers for diagnosis, demonstrating that SAA1α, SAA1β, and SAA2α variants but also S100A8 and S100A9 do not respond to all early treatment in ERA and should be rather considered as companion markers useful to improve the follow-up of treatment response and remission state. Moreover, it suggests that earlier use of biologics in addition to methotrexate may be worth considering.

Clinical and Radiographic Outcomes in Patients Diagnosed with Early Rheumatoid Arthritis in the First Years of the Biologic Treatment Era: A 10-year Prospective Observational Study

2015 ◽  
Vol 42 (12) ◽  
pp. 2279-2287 ◽  
Author(s):  
Glenn Haugeberg ◽  
Pernille Bøyesen ◽  
Knut Helgetveit ◽  
Anne Prøven
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Joint Damage ◽  
Symptom Duration ◽  
Biologic Treatment ◽  
Radiographic Outcomes ◽  
Patient Reported ◽  
Biologic Dmard ◽  
Hands And Feet

Objective.To study short-term and longterm clinical and radiographic outcomes in patients with early rheumatoid arthritis (RA) in the first decade of the biologic treatment era.Methods.Patients with early RA diagnosed at a rheumatology outpatient clinic were consecutively enrolled between 1999 and 2001. Data were collected on demographic characteristics, disease activity, patient-reported outcomes, and treatments. Radiographs of hands and feet were performed at baseline and after 2, 5, and 10 years and scored according to the Sharp/van der Heijde method, yielding a modified total Sharp score (mTSS).Results.Mean baseline age for the 94 included patients (36 men and 58 women) was 50.4 years and symptom duration 12.3 months; 67.8% were rheumatoid factor–positive. The proportion of patients in remission and in low, moderate, and high disease activity status was at baseline 4.3%, 1.1%, 35.1%, and 59.6% and at 10 years 52.1%, 20.5%, 27.4%, and 0.0%, respectively. For the period 0–2 years, 62.8% had used prednisolone, 91.5% synthetic disease-modifying antirheumatic drug (DMARD), and 18.1% biologic DMARD, and for the period 2–10 years the numbers were 50.6%, 89.3%, and 62.7%, respectively. At baseline, 70% of the patients had erosions on radiographs. Mean annual change in mTSS was for 0–2 years 3.4, 2–5 years 1.7, and 5–10 years 1.2.Conclusion.A large proportion of our patients with RA diagnosed and treated in the new biologic treatment era achieved a status of clinical remission or low disease activity and had only a minor increase in radiographic joint damage after the first years of followup.

Do Radiographic Joint Damage and Disease Activity Influence Functional Disability Through Different Mechanisms? Direct and Indirect Effects of Disease Activity in Established Rheumatoid Arthritis

2013 ◽  
Vol 40 (9) ◽  
pp. 1505-1512 ◽  
Author(s):  
Sandhya C. Nair ◽  
Johannes W.J. Bijlsma ◽  
Jacobien H. van der Werf ◽  
Maaike J. van der Veen ◽  
Suzanne P. Linn-Rasker ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Functional Disability ◽  
Functional Decline ◽  
Joint Damage ◽  
Treatment Strategies ◽  
Joint Disease ◽  
Influence Functional ◽  
Over Time ◽  
Predictive Effect

Objective.To explore the relationship between rheumatoid arthritis (RA) disease activity and functional disability over time, considering indirect (predictive) and direct (concurrent) associations as well as the influence of radiographic joint damage and treatment strategy.Methods.Functional disability [Health Assessment Questionnaire (HAQ)], disease activity [28-joint Disease Activity Score (DAS28)], and radiographic joint damage [Sharp/van der Heijde score (SHS)] were measured in 4 consecutive randomized controlled trials with increasingly intensive (tight control) treatment strategies. Average followup time for the 3 cohorts was 97, 53, and 50 months, respectively. Next to current DAS28, the previous DAS28 was used to study the predictive effect of a change in DAS28 on progression of functional disability (HAQ). Finally, it was investigated whether SHS mediated the predictive effect of DAS28.Results.In patients treated with intensive treatment strategies, the progression of HAQ over time was statistically significantly less (p < 0.0001). The predictive influence of DAS28 on HAQ progression increased over the duration of the disease. SHS was not found to influence HAQ progression and did not mediate the predictive effect of DAS28. In the less intensively treated patients, the direct effect of disease activity decreased with disease duration, and contrarily, SHS did influence HAQ progression, but was not found to (fully) mediate the predictive effect of DAS28.Conclusion.In patients with RA treated with modern treatment strategies, there is less functional decline over time. Further, disease activity does predict functional decline but joint damage does not. This might indicate that factors associated with cumulative disease activity but not visible on radiographs can influence functional decline in patients with RA. This further underlines the importance of disease activity as a treatment target in early RA and in established RA.

scholarly journals No Correlation Exists between Disease Activity and the Expression of Killer-Cell Immunoglobulin-Like Receptors in Patients with Rheumatoid Arthritis

2007 ◽  
Vol 2007 ◽  
pp. 1-4 ◽  
Author(s):  
Toshiaki Kogure ◽  
Takeshi Tatsumi ◽  
Atsushi Niizawa ◽  
Hiroshi Fujinaga ◽  
Tomoyuki Ito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Mononuclear Cells ◽  
Killer Cell ◽  
Joint Damage ◽  
Cross Sectional Study ◽  
Remarkable Change ◽  
Peripheral Blood Mononuclear ◽  
Cross Sectional ◽  
Inflammation Parameters

Objective. The genes for killer-cell immunoglobulin-like receptors (KIRs) have been cloned and their functions and expression in patients with rheumatoid arthritis (RA) have been partially clarified. However, the correlation between their expression and disease activity has not been analyzed in patients with RA. Thus, we measured KIR expression on lymphocytes in patients with RA, and assessed the correlation between KIR expression and disease activity.Patients and Methods. In the cross-sectional study, 15 patients (9 females and 6 males) who fulfilled the diagnostic criteria for RA were assessed. In the longitudinal study, patients who were followed-up for 3 months were assessed. CD158a/b expression on peripheral blood mononuclear cells (PBMC) of RA patients was analyzed using flow cytometry.Results. No significant correlation between KIR expression and CRP, ESR, or IgM-RF was observed. There was no remarkable change in the expression of KIRs between the baseline and after 3 months. Additionally, in the 5 patients whose expression of KIRs particularly changed, the time-related changes in the expression of KIRs were independent from those of inflammation parameters and IgM-RF.Conclusion. There was no correlation between KIR expression and disease activity; therefore, the clinical use of KIR expression should be limited, while unnatural KIR expression may be involved in the pathogenesis of RA, but not a recruitment of chronic inflammation to induce joint damage.

scholarly journals Fibromyalgia Is Common and Adversely Affects Pain and Fatigue Perception in North Indian Patients with Rheumatoid Arthritis

2009 ◽  
Vol 36 (11) ◽  
pp. 2443-2448 ◽  
Author(s):  
VARUN DHIR ◽  
ABLE LAWRENCE ◽  
AMITA AGGARWAL ◽  
RAMNATH MISRA
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Functional Disability ◽  
Health Assessment ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
The North ◽  
Indian Patients

Objectives.Fibromyalgia (FM) has been shown to be common in patients with rheumatoid arthritis (RA), but studies on Asian patients are lacking. It remains unclear whether FM has an adverse influence on pain, fatigue, quality of life, and mood in these patients, and what its relationship is with disease activity. We studied prevalence and effects of FM in North Indian patients with RA and associations of RA with disease activity.Methods.This cross-sectional study included 200 RA patients and an equal number of controls. Presence of FM was defined using the American College of Rheumatology 1990 criteria. Pain and fatigue scores were assessed using a 10 cm visual analog scale. Quality of life and presence of depression/anxiety were determined using validated questionnaires. Disease activity and functional disability in RA patients was assessed using the Disease Activity Score 28-3 and Health Assessment Questionnaire, respectively.Results.FM was present in 15% of patients with RA compared to 2.5% of controls in the North Indian population. RA patients with FM did not differ from those without FM in terms of age, gender, current disease-modifying agents, or steroid use. RA patients with FM had higher disease activity and worse functional disability. The number of tender and swollen joints was higher in patients with FM, but correlated poorly with each other. RA patients with FM had higher pain and fatigue scores but were not different in the quality of life or mood.Conclusion.FM is more common in North Indian patients with RA compared to controls. It adversely affects the pain and fatigue felt by RA patients. Disease activity and FM influence each other.

Characterization of Cumulative Joint Damage Patterns in Patients with Rheumatoid Arthritis: A Clinical, Serological, and Gene Polymorphism Perspective

2015 ◽  
Vol 42 (3) ◽  
pp. 405-412
Author(s):  
Renata Trigueirinho Alarcon ◽  
Artur da Rocha Corrêa Fernandes ◽  
Ieda Maria Laurindo ◽  
Manoel Barros Bértolo ◽  
Geraldo Castelar Pinheiro ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Polymorphism ◽  
Triple Negative ◽  
Shared Epitope ◽  
Joint Damage ◽  
Morphometric Features ◽  
Anticitrullinated Protein Antibodies ◽  
Se Status

Objective.To characterize cumulative joint damage (CJD) patterns in rheumatoid arthritis (RA) and determine their associations with demographic/clinical features and HLA-DRB1 gene polymorphism.Methods.Hand and foot radiographs were obtained from 404 patients with RA. CJD patterns were determined by 3 derivations from Sharp/van der Heijde scores, obtained by the mathematical division of scores for hands/feet (Sharp-h/f score), fingers/wrists (Sharp-f/w score), and erosion/space narrowing (Sharp-e/sn score), respectively. DNA and serum were obtained for determination of HLA-DRB1 polymorphism, rheumatoid factor (RF), and anticitrullinated protein antibodies (ACPA).Results.Patients with wrist-dominant CJD pattern were more likely to have severe RA than those with finger-dominant pattern (68.4% vs 46.0%; p = 0.036) as were those with foot-dominant vs hand-dominant CJD pattern (76.5% vs 56.4%; p = 0.044). HLA-DRB1 shared epitope (SE) alleles were associated with erosion-dominant CJD pattern (p = 0.021). Patients with erosion-dominant CJD pattern had higher levels of RF and ACPA than those with space-narrowing–dominant CJD pattern (median RF 71.35 U/ml vs 22.05 U/ml, respectively; p = 0.003; median ACPA 187.9 U/ml vs 143.2 U/ml, respectively; p < 0.001). The majority of triple-positive patients (SE+, RF+, ACPA+) had erosion-dominant CJD pattern (62.3%) while the majority of triple-negative patients (SE–, FR–, ACPA–) had space narrowing–dominant CJD pattern (75%; p = 0.017). ACPA was associated with HLA-DRB1 SE alleles (p < 0.05). Patients with foot-dominant CJD pattern were taller than those with hand-dominant CJD pattern (p = 0.002); those with erosion-dominant CJD pattern had higher weight and body mass index than those with space narrowing–dominant CJD pattern (p = 0.014, p = 0.001).Conclusion.CJD patterns were associated with disease severity, HLA-DRB1 SE status, presence and titer of ACPA and RF, and morphometric features.

scholarly journals Molecular Changes in the Adipose Tissue Induced by Rheumatoid Arthritis: Effects of Disease-Modifying Anti-Rheumatic Drugs

2021 ◽  
Vol 12 ◽  
Author(s):  
Iván Arias de la Rosa ◽  
Alejandro Escudero-Contreras ◽  
Miriam Ruiz-Ponce ◽  
Cristóbal Román-Rodríguez ◽  
Carlos Pérez-Sánchez ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adipose Tissue ◽  
Disease Activity ◽  
Joint Damage ◽  
Response To Therapy ◽  
Metabolic Effects ◽  
Obese Mouse ◽  
Molecular Changes ◽  
Moderate Disease ◽  
Disease Modifying

Disease severity, progression and response to therapy might be worse in obese rheumatoid arthritis (RA) patients, but paradoxically, obesity also might protect from radiographic joint damage. Thus, the intricate relationship between obesity and RA needs urgent clarification. The aim of this study was to assess the influence of obesity on the onset and development of RA and to determine whether arthritis could modify the adipose tissue biology and whether conventional Disease Modifying Anti-Rheumatic Drugs (cDMARDs) can modulate these alterations. Two strategies were followed: (1) clinical profiling of two cohorts of RA: non-obese and obese patients; and (2) mechanistic studies carried out in both a collagen-induced arthritis (CIA) in an obese mouse model and 3T3-L1 adipocytes treated with cDMARDs (leflunomide, methotrexate, and hydroxychloroquine). In our cohort of RA patients with low-moderate disease activity, the presence of obesity was not related to a higher activity of the disease; actually, disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) was reduced in the obese RA patients. However, the induction of arthritis promoted transcriptomic changes in the adipose tissue under obesity condition in the obese CIA model. Treatment with hydroxychloroquine reduced weight and insulin resistance, accompanied by beneficial metabolic effects in the adipose tissue. These molecular changes in adipose tissue were also observed after methotrexate administration. In sum, arthritis might affect directly the inflammatory burden and metabolic alterations associated with obesity in adipose tissue. Clinicians should be cautious measuring the activity of the disease in obesity and managing the best therapeutic options for the metabolic comorbidities of these patients, where the combination of hydroxychloroquine and methotrexate should be considered to improve adipose tissue dysfunction in obese RA.

Spinal sagittal balance associated with age, vertebral fracture, and functional disability in patients with rheumatoid arthritis: A cross-sectional study

2019 ◽  
Vol 30 (6) ◽  
pp. 1002-1008 ◽  
Author(s):  
Takeshi Mochizuki ◽  
Koichiro Yano ◽  
Toshiyuki Shirahata ◽  
Katsunori Ikari ◽  
Ryo Hiroshima ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Vertebral Fracture ◽  
Sagittal Balance ◽  
Functional Disability ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional

scholarly journals Contribution of Multiplex Immunoassays to Rheumatoid Arthritis Management: From Biomarker Discovery to Personalized Medicine

2020 ◽  
Vol 10 (4) ◽  
pp. 202
Author(s):  
Carlos M. Laborde ◽  
Patricia Castro-Santos ◽  
Roberto Díaz-Peña
Keyword(s):  
Rheumatoid Arthritis ◽  
Personalized Medicine ◽  
Physical Disability ◽  
Functional Disability ◽  
Biomarker Discovery ◽  
Joint Damage ◽  
Cartilage Destruction ◽  
Local Inflammation ◽  
Protein Biomarkers ◽  
Low Sensitivity

Rheumatoid arthritis (RA) is a multifactorial, inflammatory and progressive autoimmune disease that affects approximately 1% of the population worldwide. RA primarily involves the joints and causes local inflammation and cartilage destruction. Immediate and effective therapies are crucial to control inflammation and prevent deterioration, functional disability and unfavourable progression in RA patients. Thus, early diagnosis is critical to prevent joint damage and physical disability, increasing the chance of achieving remission. A large number of biomarkers have been investigated in RA, although only a few have made it through the discovery and validation phases and reached the clinic. The single biomarker approach mostly used in clinical laboratories is not sufficiently accurate due to its low sensitivity and specificity. Multiplex immunoassays could provide a more complete picture of the disease and the pathways involved. In this review, we discuss the latest proposed protein biomarkers and the advantages of using protein panels for the clinical management of RA. Simultaneous analysis of multiple proteins could yield biomarker signatures of RA subtypes to enable patients to benefit from personalized medicine.

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