Deterioration In Rheumatoid Arthritis Research Articles

Clinico Pathological Study of Rheumatoid Arthritis Association with C -Reactive Protein (CRP); a Potential Biomarker of Cartilage Damage

Objective: To explore the association between rheumatoid arthritis (RA) and C-reactive protein (CRP) levels as a potential biomarker of cartilage damage. Methodology: This case control study was done at Department of pathology Ziauddin University Clifton Campus, Karachi from June 2018 to May 2019. Patients diagnosed with rheumatoid arthritis (RA) according to established criteria, aged 18 years or older and both male and female participants were included. Clinical data was collected through medical record review and direct patient interviews. Blood samples were collected from participants for CRP measurement using standard laboratory assays. Serum CRP levels were quantified using high-sensitivity CRP assays in a certified clinical laboratory. CRP levels was defined based on established cutoff values, typically exceeding 3 mg/L. Statistical Analysis: Statistical analysis will be performed using SPSS version 26. Results: Mean age of patients was 43.38+.56 years, while control group subjects had a slightly lower mean age of 42.33+6.93 years (p = 0.412). Gender distribution showed a predominant female representation, with 76 female patients (88.4%) and 75 female controls (87.2%) (p = 0.816). There was a strong positive correlation was observed between DAS28 and CRP levels, with a Pearson correlation coefficient of r= 0.745 and (p < 0.01), indicating a significant association between disease activity and CRP concentration. Conversely, the correlation between DAS28 and ESR was weaker and not statistically significant (r = 0.123, p = 0.258). Conclusion: Study revealed that the significant elevation of serum CRP levels in RA patients compared to healthy individuals. The positive correlation between serum CRP levels and the extent of joint damage observed radiographically, suggesting CRP's potential as a biomarker for estimating disease severity and cartilage deterioration in RA.

Natural compound library screening to identify berberine as a treatment for rheumatoid arthritis.

Fibroblast-like synoviocytes (FLS) play a critical role on the exacerbation and deterioration of rheumatoid arthritis (RA). Aberrant activation of FLS pyroptosis signaling is responsible for the hyperplasia of synovium and destruction of cartilage of RA. This study investigated the screened traditional Chinese medicine berberine (BBR), an active alkaloid extracted from the Coptis chinensis plant, that regulates the pyroptosis of FLS and secretion of inflammatory factors in rheumatoid arthritis. First, BBR was screened using a high-throughput drug screening strategy, and its inhibitory effect on RA-FLS was verified by in vivo and in vitro experiments. Second, BBR was intraperitoneally administrated into the collagen-induced arthritis rat model, and the clinical scores, arthritis index, and joint HE staining were evaluated. Third, synovial tissues of CIA mice were collected, and the expression of NLRP3, cleaved-caspase-1, GSDMD-N, Mst1, and YAP was detected by Western blot. The administration of BBR dramatically alleviated the severity of collagen-induced arthritis rat model with a decreased clinical score and inflammation reduction. In addition, BBR intervention significantly attenuates several pro-inflammatory cytokines (interleukin-1β, interleukin-6, interleukin-17, and interleukin-18). Moreover, BBR can reduce the pyroptosis response (caspase-1, NLR family pyrin domain containing 3, and gasdermin D) of the RA-FLS in vitro, activating the Hippo signaling pathway (Mammalian sterile 20-like kinase 1, yes-associated protein, and transcriptional enhanced associate domains) so as to inhibit the pro-inflammatory effect of RA-FLS. These results support the role of BBR in RA and may have therapeutic implications by directly repressing the activation, migration of RA-FLS, which contributing to the attenuation of the progress of CIA. Therefore, targeting PU.1 might be a potential therapeutic approach for RA. Besides, BBR inhibited RA-FLS pyroptosis by downregulating of NLRP3 inflammasomes (NLRP3, caspase-1) and eased the pro-inflammatory activities via activating the Hippo signaling pathway, thereby improving the symptom of CIA.

Inflammation‐Instructed Hierarchical Delivery of IL‐4/miR‐21 Orchestrates Osteoimmune Microenvironment toward the Treatment of Rheumatoid Arthritis

AbstractDysregulated inflammation and failure in resolution account for the incidence and deterioration of rheumatoid arthritis (RA). IL‐4 and miR‐21 possess complementary functions in inhibiting inflammation and fostering resolution. Thus, inflammation‐instructed nanocomplexes (NCs) are herein developed to mediate hierarchical co‐delivery of miR‐21 and IL‐4 to orchestrate the osteoimmune microenvironment against RA. The NCs comprise a cationic inner core assembled from the membrane‐penetrating, helical polypeptide (PG) and miR‐21, an outer layer based on the acid‐responsive, charge reversal polymer (PLL‐CA), and surface‐adsorbed IL‐4. The negatively charged NCs enable prolonged blood circulation after systemic administration, and thus passively accumulate in the inflamed joint. In the slightly acidic microenvironment of inflamed synovium, PLL‐CA transforms from negative to positive, which sheds off to liberate IL‐4 extracellularly and facilitate the intracellular delivery of the PG/miR‐21 core into macrophages. Thus, the anti‐inflammatory miR‐21 cooperates with the proresolving IL‐4 to attenuate inflammation via NF‐κB inhibition, promote macrophage polarization to M2a/M2c phenotypes, propel resolution, and promote tissue repair against Zymosan A‐induced arthritis. This study provides an effective strategy toward the programmed delivery of drug/gene cargoes at different extracellular/intracellular locations, and the combined mechanism of anti‐inflammation and proresolution renders insights into the treatment of inflammatory diseases.

SAT0180 Subclinical Inflammation in Rheumatoid Arthritis (RA) in Clinical Remission, Lack of Association between Cytokines Level and Ultrasound-Defined Synovitis

BackgroundThe presence of subclinical inflammation promotes the progression of morphostructural joint damage in RA patients. Currently, clinical remission is based on the count of swollen and painful joints associated with...

Outcome of surgery for rheumatoid cervical spine at one institute over three decades

Background contextSurgical intervention is a therapeutic choice for atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS) associated with rheumatoid cervical spine. However, the long-term outcomes of different subgroups remain unclear, although rheumatoid arthritis (RA) is a progressive disease even after surgery. PurposeTo evaluate the outcomes of surgery for various subgroups of rheumatoid cervical spine, performed at a single institute over three decades. Study designRetrospective clinical analysis. Patient sampleOne-hundred eighteen seropositive RA patients treated at one institute over the past three decades. Atlantoaxial fixation was performed in 28 AAS patients. Occipitospinal fusion was performed in 41 irreducible AAS or VS patients. Laminotomy with autologous bone fusion was performed in 22 patients, anterior fusion in 5, laminoplasty in 4, and posterior decompression/fusion with instrumentation in 12 with SAS. MethodsClinical outcomes using the Japanese Orthopedic Association score, complications, deterioration of RA, and mortality rate during the follow-up were investigated from preoperation to more than 10 years after surgery in the subgroups. Outcome measuresOutcomes were compared among the subgroups. ResultsPatients with AAS exhibited significantly better clinical outcomes throughout the follow-up period compared with patients from the other subgroups. Patients with SAS had the worst neurologic status even at preoperation, and the symptomatic improvement achieved by surgery deteriorated within less than 5 years. Deterioration of outcome was caused by occurrence of complications and deterioration of RA during the follow-up. The mortality rates at 5 and 10 years after surgery were 20% and 33%, respectively. ConclusionsThe outcome of surgery for rheumatoid cervical spine was different in the various subgroups and associated with the occurrence of complications and deterioration of RA.

SAT0408 Both clinical and ultrasonographic evaluation of synovitis are relevant to predict subsequent radiological deterioration in rheumatoid arthritis

BackgroundPresence of synovitis has been demonstrated to be predictive of subsequent structural deterioration in rheumatoid arthritis (RA). In comparison to physical examination, ultrasonography (US) seems to be more accurate (sensitive)...

FRI0065 Residual power doppler signals during clinical remission determine joint prognosis in rheumatoid arthritis

Background“Clinical remission” has been a realistic goal of treatment in rheumatoid arthritis (RA). However, there is evidence that subclinical synovitis is associated with progression of structural damage even after achieving...

FRI0477 Validity of contrast-enhanced ultrasound (CEUS) in the detection of synovial inflammation in rheumatoid arthritis compared to power doppler in contrast-enhanced mri controlled pilot study

BackgroundThe treatment of rheumatoid arthritis (RA) aims clinical remission and arrest of radiological damage. Clinical evaluation alone results inadequate in assessing disease activity, and imaging studies have become integrative assessment...

FRI0130 Change in disease outcomes after implementation of treat to target, including evaluation of power doppler ultrasound remission

BackgroundThe 2010 treatment to target guidelines recommend frequent assessment to achieve a pre-defined target (ideally remission) in early rheumatoid arthritis (RA) [1]. Power Doppler (PD) ultrasound has the ability to...

THU0156 Response of ra on MRI-detected synovitis to double filtration plasmapheresis

BackgroundRheumatoid arthritis (RA) is a chronic systemic inflammatory disease with a poor prognosis in which synovitis induces progressive destruction of bones and joints, which leads to marked impairment of the...

SAT0520 Ultrasonography is Useful for Predicting Boolean Remission after Achieving DAS28-Based Clinical Remission of Rheumatoid Arthritis

BackgroundAlthough “clinical remission” has been a realistic goal of treatment in rheumatoid arthritis (RA), its definition is still controversial. In fact, progressive joint destruction is often observed even during persistent...

An Explanation for the Apparent Dissociation Between Clinical Remission and Continued Structural Deterioration in Rheumatoid Arthritis

An Explanation for the Apparent Dissociation Between Clinical Remission and Continued Structural Deterioration in Rheumatoid Arthritis

An explanation for the apparent dissociation between clinical remission and continued structural deterioration in rheumatoid arthritis

Achieving remission is the aim of treatment in rheumatoid arthritis (RA). This should represent minimal arthritis activity and ensure optimal disease outcome. However, we have previously demonstrated a high prevalence of imaging-detected synovial inflammation in RA patients who were in clinical remission. The purpose of this study was to evaluate the long-term significance of subclinical synovitis and its relationship to structural outcome. We studied 102 RA patients receiving conventional treatment who had been judged by their consultant rheumatologist to be in remission, as well as 17 normal control subjects. Subjects underwent clinical, laboratory, functional, and quality of life assessments over 12 months. In addition to standard radiography of the hands and feet, imaging of the hands and wrists was performed with musculoskeletal ultrasonography (US) and conventional 1.5 T magnetic resonance imaging (MRI) at baseline and 12 months, using validated acquisition and scoring techniques. Despite their being in clinical remission, 19% of the patients displayed deterioration in radiographic joint damage over the study period. Scores on musculoskeletal US synovial hypertrophy, power Doppler (PD), and MRI synovitis assessments in individual joints at baseline were significantly associated with progressive radiographic damage (P=0.032, P<0.001, and P=0.002, respectively). Furthermore, there was a significant association between the musculoskeletal US PD score at baseline and structural progression over 12 months in totally asymptomatic metacarpophalangeal joints (P=0.004) and 12 times higher odds of deterioration in joints with increased PD signal (odds ratio 12.21, P<0.001). Subclinical joint inflammation detected by imaging techniques explains the structural deterioration in RA patients in clinical remission who are receiving conventional therapy. Our findings reinforce the utility of imaging for the accurate evaluation of disease status and the prediction of structural outcome.

Clinical improvement and radiological deterioration in rheumatoid arthritis: evidence that the pathogenesis of synovial inflammation and articular erosion may differ.

The contrast between clinical improvement and radiological deterioration in rheumatoid arthritis (RA) is striking. We characterized this relationship using serial disease activity measures and radiographs of hands and feet in 40 RA patients observed over 6 yr. All disease activity measures improved, including grip strength, Ritchie index (RI), haemoglobin and erythrocyte sedimentation rate (ESR) (all P < 0.0001). In contrast, articular erosion increased (P < 0.0001). Radiological change during the study correlated with RI (r = 0.49), haemoglobin (r = -0.56) and ESR (r = 0.53). Radiological status at review also correlated with these variables (r = 0.36, -0.44 and 0.36, respectively). Articular erosion continues in RA despite clinical improvement and is accelerated in those with evidence of continuing synovial inflammation, reflected in clinical and laboratory measures of disease activity. Since many therapies in RA suppress inflammation, but not erosion, these findings suggest that the pathogenesis of articular erosion may differ from that of synovial inflammation.