Inactive Rheumatoid Arthritis Research Articles

Quality of life and strength, but not cytokines, are associated with DAS-28 in active and inactive rheumatoid arthritis

Objective: Evaluate and correlate data between relevant cytokines, disease progression, and handgrip and quality of life among RA patients at different stages of disease progression. Method: Thirty-three RA patients were recruited for analysis, using comparisons and correlations, between levels of circulating cytokines (IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17, IL-1β, and TNF receptors I and II), activity of the disease (evaluated using the DAS-28), handgrip (Hydraulic dynamometer), and quality of life (SF-36). Result: RA patients in different disease stages showed increases of IL-6 and IL-10 compared control group. Positive correlation between IL-6 with TNF-α, and IL-4 with IL-10 was found. Handgrip strength and quality of life were not related to cytokine levels. However, remission patients had better strength and quality of life indices compared to the active patients. In addition, handgrip of the non-dominant side, physical functions, role limitations physical health, pain, energy/fatigue and social functions have a negative correlation with the DAS28-PCR. Conclusion: High levels of IL-6 and IL-10 were observed in the chronic RA patients, but the values did not show correlation with disease activity, handgrip strength and quality of life. Disease activity show correlation with handgrip strength and quality of life. Furthermore, remission patients had better strength and quality of life indices compared to the active patients.

CCR9+CD4+ T cells are associated with disease activity in patients with rheumatoid arthritis.

An increase in CD4+ T cells in the synovium is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify the possible causes of the elevated CD4+ T cell levels and to explore the factors influencing disease activity in RA. Fifty-five RA patients, including 28 with active RA (ARA), 27 with inactive RA, and 22 healthy controls, were recruited for this study. The proportion of CCR9+CD4+ T cells and the expression of chemokine receptor 9 (CCR9) on CD4+ T cells were analyzed by flow cytometry. Enzyme-linked immunosorbent assay and chemiluminescent immunoassay were used to evaluate interleukin (IL)-17A and IL-6 levels, respectively. The proportion of CCR9+CD4+ T cells and the expression of CCR9 on CD4+ T cells increased significantly in peripheral blood (PB) and synovial fluid (SF) in ARA compared to those in inactive RA. Furthermore, SF contained more CCR9+CD4+ T cells, IL-6, and IL-17A than PB in RA patients. Moreover, CD4+ T cells in the PB of patients with RA, especially ARA, expressed more CCR9 and secreted more IL-6 and IL-17A after activation. Here, we also demonstrated that both the percentage of CCR9+ cells in CD4+ T cells and the expression of CCR9 on circulating CD4+ T cells were positively correlated with erythrocyte sedimentation rate, hypersensitive C-reactive protein, rheumatoid factor, and anti-cyclic citrullinated peptide antibody. CCR9+CD4+ T cells are elevated in PB and SF, and are associated with disease activity in patients with RA.

Biology of tongue coating in different disease stages of RA and its value in disease progression

ObjectiveTo assess and compare the composition of tongue coating microbiota among patients at different stages of rheumatoid arthritis (RA). MethodsA total of 47 patients diagnosed with RA, as per the American College of Rheumatology criteria, and 10 healthy individuals were enrolled in this study. The RA patients were stratified considering their Disease Activity Score 28 (DAS28), a composite measure based on the 28 tender and swollen joint count and erythrocyte sedimentation rate (ESR). The study population was further categorized into active phase group (LMH group) and inactive phase group (RE group) according to their DAS28 values. DNA extraction was extracted from tongue coating samples. Subsequently, the V3–V4 16S rDNA region was selectively amplified and sequenced through high-throughput 16S rDNA analysis. The resulting data were then utilized to ascertain the microbial contents. ResultsSignificant variations were observed in the tongue coating microbiota of patients with RA during active and inactive phases, in comparison to healthy individuals (p < 0.05). At the genus level, the presence of Prevotellan, Veillonella, Rothia, and Neisseria in RA patients was notably more evident than in the healthy control (HC) group. These disparities find support in existing research on gut and oral microbiota. During the active phase of RA, the relative abundance of Veillonella, Rothia, and Neisseria in the tongue coating microbiota of patients was significantly higher than in those with inactive RA. These findings underscore the need for further and in-depth research on the potential impact of these microorganisms on the progression of RA disease. ConclusionThe results substantiate the hypothesis that tongue coating microbes actively contribute to the progression of RA.

Association of soluble triggering receptor expressed on myeloid cells-1 with rheumatoid arthritis in Iraqi patients: A case-control study.

Rheumatoid arthritis (RA) is a common chronic immune-mediated inflammatory arthritis, impacting 0.5-1% of the global population, and leading to progressive deterioration of the musculoskeletal and joint systems. This study aims to analyze the serum levels of soluble triggering receptors expressed on myeloid cells-1 (sTREM-1) in Iraqi patients with RA and healthy individuals. It also intends to assess the diagnostic significance of these receptors, investigate their association with disease activity and examine their correlation with the sociodemographic and clinical characteristics of the patients. From December 2020 to June 2021, 117 RA patients with a mean age of 50 years participated in the study. The patients were categorized into inactive and active disease groups based on their DAS28 score and CDAI, as determined by a Rheumatologist. The serum levels of a specific triggering receptor expressed on myeloid cells-1 (TREM-1) (Pg/mL) were measured. The results showed that the active RA patients had significantly higher levels of the receptor (270.17±187) compared to both the inactive RA patients (112.81±37.48) and the healthy controls (43.89±29.53) (P < 0.001). The sTREM-1 demonstrated a high discriminatory ability (AUC ≥ 0.936) between RA and control groups. Moreover, a direct association was observed between the DAS-28ESR and sTREM-1 levels.

Three-dimensional Echocardiography for the Early Detection of Cardiac Dysfunction in Patients with Rheumatoid Arthritis

Abstract Background Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease. Left atrial (LA) dysfunction is strongly linked to cardiovascular diseases, and the early detection of LA function in patients with RA is vital. Real-time three-dimensional echocardiography (RT-3DE) offers a noninvasive method to assess the structure and function of the LA. Aim of the study To assess LA volumes and phasic function in patients with RA using 3D transthoracic echocardiography. Materials and Methods This prospective case-control study included 162 subjects classified into two groups: Group 1 included 82 patients with RA, subdivided into an active RA group (n = 40) and an inactive RA group (n = 42), and Group 2 included 80 healthy matched controls. All study participants were examined using 2D and 3D transthoracic echo-cardiography. Results Diastolic dysfunction was significantly greater in patients with moderate and severe disease activity than in patients with mild disease activity. RT-3DE analysis of RA groups showed significantly higher maximum, minimum, and pre-atrial LA volumes compared to controls (p &lt;0.01), and these volumes were significantly higher in the active RA group than in the inactive RA group (p &lt;0.01). We also found significantly lower LA passive ejection fraction (EF) and active EF in both RA groups than the control group (p &lt;0.01), and significantly lower total EF in the active RA group than the inactive RA group (p &lt;0.01). Conclusion Patients with RA had increased 3D LA volumes and impaired mechanical function, especially in active RA. RT-3DE provides an accurate measurement of LA volumes and function, being a feasible and reproducible method in clinical applications.

Neutrophil extracellular traps: features of their formation in rheumatoid arthritis and osteoarthritis

The similarity of clinical manifestations and some pathogenetic mechanisms in rheumatoid arthritis (RA) and osteoarthritis (OA) is of particular interest in studying the features of extracellular neutrophil traps (NETs) formation in these musculoskeletal diseases. Our objective was to evaluate circulating neutrophil extracellular trap formation related to autoimmune inflammation in RA and reactive inflammation in OA.39 RA patients comprised the main group; 35 OA patients, control group; 33 healthy individuals were included into the reference group. Circulating neutrophils were isolated by the one-step centrifugation in double layer of iohexol density gradient. NETs were induced by phorbol-12-myristate-13–acetate (PMA) being visualized by fluorescence microscopy.The RA disease activity at the inclusion period should not exceed 2.6 DAS28 points. ОA patients were in clinical remission at the inclusion timepoint. In 17 RA patients, an increase in DAS28 exceeded 3.2 points; in 25 OA patients, an exacerbation was diagnosed during the study. The mean percentage of spontaneous and induced NETs in reference group was 3.8% (2.6-5.0) and 12.2% (9.0-15.4), respectively. Appropriate values for the patients with inactive RA were 5.9% (5.6-6.2) and 26% (23.9-28.1); 16.6% (16.1-17.1) and 38.0% (36.6-39.4) in active RA cases, respectively; 5.4% (5.2-5.6) and 20.3% (18.3-22.3) in OA without synovitis; 13.1% (12.6-18.1) and 28.3% (6. 4-30.2) in OA with synovitis, respectively. Spontaneous increase of NETs during RA activation was 181.4%; induced increase in NETs was 46.2%; and in cases of OA exacerbation these values were 142.6% and 39.4%, respectively. In RA patients, the rates of spontaneous NETs formation were 3.9 times higher than for induced values. Appropriate index was 3.6 times higher among the OA patients. The increase in spontaneous -to-induced NETs formation was more pronounced in active RA than in OA with synovitis. The main difference in NETs composition for active RA patients (in 88% of cases) and OA synovitis (in 50% of cases) is related to the contents of citrulline epitopes (p = 0.03).Transition of RA from the remission state to active inflammation, as well as OA exacerbation are accompanied by a significant increase in NETs, especially, spontaneous formation. The degree of increase in RA was higher than in OA, thus, probably, indicating higher involvement of neutrophils in generation of NETs during autoimmune inflammation rather than in reactive inflammation. A sufficient role of citrullinated epitopes in NETs demonstrates their influence upon induction and maintenance of autoimmune response to RA-specific autoantigens.

Increased expression of long-isoform thymic stromal lymphopoietin is associated with rheumatoid arthritis and fosters inflammatory responses.

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine that is involved in the pathogenesis of inflammatory diseases and asthma, but the expression and biological implications of the existence of two isoforms, long TSLP (lTSLP) and short TSLP (sTSLP), in RA have yet to be elucidated. Here we report that lTSLP is the predominant TSLP isoform in RA and active RA, whereas sTSLP is the major TSLP isoform in inactive RA and healthy controls. lTSLP expression is associated with disease activity, including 28-joint Disease Activity Score (DAS28) and erythrocyte sedimentation rate (ESR), as well as proinflammatory cytokine expression, irrespective of other laboratory parameters. Importantly, lTSLP alone or combined with LPS promotes the expression of proinflammatory cytokines IL-1β, IL-6, and IL-8 in PBMCs of RA, but restrains anti-inflammatory cytokine IL-10 expression in PBMCs of RA. Furthermore, we found that STAT5 signaling is involved in lTSLP-induced inflammatory accumulation in PBMCs of RA. Therefore, these results highlight the clinical significance of lTSLP in RA pathology and inflammatory response in acute-phase disease, which may provide a therapeutic target for RA.

Evaluation of the role of hydroxychloroquine as a lipid profile improving and glucose adjusting drug in Egyptian females with inactive rheumatoid arthritis

Evaluation of the role of hydroxychloroquine as a lipid profile improving and glucose adjusting drug in Egyptian females with inactive rheumatoid arthritis

Evaluation of circulating miR-16-5p and miR-223-5p in association with musculoskeletal ultrasonography seven-joint score in the assessment of rheumatoid arthritis activity

Rheumatoid arthritis (RA) is characterized by ongoing joint destruction. MicroRNAs (miRs) are blood-based biomarkers linked to RA pathogenesis. The musculoskeletal ultrasonography seven-joint score (US7) is an objective tool to assess RA activity. We aimed to evaluate miR-223 and miR-16 roles in monitoring RA activity and to investigate if there is a link between their plasma levels and US7 score. This study enrolled 76 RA patients classified according to Disease Activity Score 28-joint count with erythrocyte sediment rate (DAS28-ESR) to inactive cases (n = 38) and active cases (n = 38). Each patient's joint was scored for synovial proliferation (gray-scale ultrasound 'GSUS7') and vascularization (power Doppler ultrasound 'PDUS7'). Real-time quantitative PCR was used to measure the expression levels of miR-16 and miR-223 in plasma. When compared to inactive group, the active group revealed significant upregulation of miR-16 and miR-223, (P = 0.001 and P = 0.02, respectively). miR-16 and miR-223 levels were correlated with synovitis PDUS7 (r = 0.34, p < 0.01 and r= 0.25, P = 0.03, respectively). miR-16 was also positively correlated with synovitis GSUS7 (r= 0.42, p < 0.001). miR-223 upregulation discriminated active from inactive RA patients at AUC = 0.64, with 76% sensitivity and 50% specificity at cutoff > 2.8-fold change), whereas miR-16 distinguished the two groups at AUC = 0.78 with 87% sensitivity and 53% specificity at cutoff >38.27-fold change. In conclusion, upregulated miR-16 may have more potential to serve as activity biomarkers than miR-223 in RA. The miR-16 level was linked to synovitis GSUS7 and synovitis PDUS7 changes but miR-223 only linked to synovitis PDUS.

Fully automatic software for detecting radiographic joint space narrowing progression in rheumatoid arthritis: phantom study and comparison with visual assessment.

We have developed an in-house software equipped with partial image phase-only correlation (PIPOC) which can automatically quantify radiographic joint space narrowing (JSN) progression. The purpose of this study was to evaluate the software in phantom and clinical assessments. In the phantom assessment, the software's performance on radiographic images was compared to the joint space width (JSW) difference using a micrometer as ground truth. A phantom simulating a finger joint was scanned underwater. In the clinical assessment, 15 RA patients were included. The software measured the radiological progression of the finger joints between baseline and the 52nd week. The cases were also evaluated with the Genant-modified Sharp score (GSS), a conventional visual scoring method. We also quantitatively assessed these joints' synovial vascularity (SV) on power Doppler ultrasonography (0, 8, 20 and 52weeks). In the phantom assessment, the PIPOC software could detect changes in JSN with a smallest detectable difference of 0.044mm at 0.1mm intervals. In the clinical assessment, the JSW change of the joints with GSS progression detected by the software was significantly greater than those without GSS progression (p = 0.004). The JSW change of joints with positive SV at baseline was significantly higher than those with negative SV (p = 0.024). Our in-house software equipped with PIPOC can automatically and quantitatively detect slight radiographic changes of JSW in clinically inactive RA patients.

COVID-19 vaccination in autoimmune diseases (COVAD) study: vaccine safety and tolerance in rheumatoid arthritis.

The COVID-19 vaccination in autoimmune diseases (COVAD) study aimed to assess short-term COVID-19 vaccination-related adverse events (AEs) in RA patients. An online self-reported questionnaire (March-December 2021) was used to capture data related to COVID-19 vaccination-related AEs in RA, other autoimmune rheumatic diseases (AIRDs) (excluding RA and inflammatory myositis), non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs). Descriptive and multivariable regression analyses were performed. Of the 9462 complete respondents, 14.2% (n = 1347) had been diagnosed with RA; they had a mean (s.d.) age of 50.7 (13.7) years, 74.2% were women and 49.3% were Caucasian. In total, 76.9% and 4.2% of patients with RA reported minor and major AEs, respectively. Patients with active and inactive RA had similar AE and hospitalization frequencies. Overall, AEs were reported more frequently by BNT162b2 and mRNA-1273 recipients and less frequently by BBV152 recipients compared with the rest. Major AE and hospitalization frequencies were similar across recipients of different vaccines. Patients receiving methotrexate and hydroxychloroquine reported fewer minor AEs than those patients not on them. Compared with HCs and patients with other AIRDs, patients with RA reported similar total AEs, overall minor AEs, and hospitalizations. Compared with nrAIDs, patients with RA reported lower frequencies of overall AEs, minor AEs (both odds ratio [OR] = 0.7; 95% CI: 0.5, 0.9), and injection site pain (OR = 0.6; 95% CI: 0.5, 0.8) with similar major AE and hospitalization frequencies. Despite the differences in AE frequency across different COVID-19 vaccines, all were well tolerated in patients with RA and were comparable to HCs, providing reassurance as to the safety of COVID-19 vaccination.

Fibroblast growth factor 23 (Fgf23) levels and their relationship with disease activity, bone mineral density, and radiological damage score in patients with rheumatoid arthritis: a single center case–control study

BackgroundThere is limited and conflicting information on Fgf23 levels and their relationship with bone loss and disease activity in rheumatoid arthritis (RA). The aim of this study was to compare Fgf23 levels in RA patients with a healthy population and to evaluate the relationship between Fgf23 levels in RA with disease activity, bone mineral density (BMD), and radiological damage score.ResultsThe median Fgf23 levels in patients with RA and in hospital staff were 20.06 (11.2–51.0) and 26.40 (12.6–49.5) pg/ml (P < 0.001), respectively. RA patients were divided into active (DAS28 > 3.2) and inactive (DAS28 ≤ 3.2) subgroups. The median Fgf23 levels in active and inactive RA patients were 22.12 (13.90–51.02) and 17.71 (11.20–31.19) pg/ml, respectively (P = 0.001). BMD of RA patients was evaluated with dual-energy X-ray absorptiometry and radiological damage scores were evaluated independently by two investigators using the modified Sharp score (MSS). In RA patients, Fgf23 values correlated with DAS28 and with erosion score of observer-2 (r = 0.297, P = 0.036), but not with erosion score of observer-1 (r = 0.252, P = 0.077). No correlation was found between DAS28 and femur and lumbar vertebra BMD.ConclusionIn RA, Fgf23 is not associated with BMD but may be associated with local bone loss and disease activity.

TH SUBSETS AND SERUM CYTOKINES IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is a systemic inflammatory disease. It is characterized by damage of cartilages and bones which results in destruction of joint function. Multi-organic disorders of lung, heart and kidney can be developed in time. Complex network of immune and stromal cells, cytokines and chemokines produced by these cells participate in onset of the disease, in the systemic active phase and during the transition to more localized inactive disease after the treatment. To evaluate the Th1, Th17, Tregs and CD4+CD39+ cells pattern and pro- and anti-inflammatory cytokines in peripheral blood of patients with RA, 47 RA patients and 20 healthy individuals were included in the study. RA patients were divided into active and inactive RA groups. Frequencies of circulating Th1, Th17, Tregs and CD4+CD39+ cells were analyzed by flow cytometry. Serum levels of cytokines: IL-6, IL-10, IL-4, IL-17, TNF-a and TGF-b1 were detected by ELISA. The results demonstrated an increase of Th1, Th17 cell frequencies in active RA patients, whereas Tregs remain unchanged in RA groups. CD39 marker expression shows significant decline in active RA patients in comparison with inactive RA group and controls. Concentrations of innate cytokines IL-6, TNF-a in the peripheral blood was significantly increased in active RA while according to IL-17/IL-21 serum concentration this group was divided into two subgroups. Anti-inflammatory cytokines TGF-b, IL-4 shows decrease in active RA group compared to healthy controls. Study demonstrated that development of RA is associated with changes of serum pro- and anti-inflammatory cytokines which influence balance of T helpers subsets and could provide therapeutic opportunities.

Potential role of HBV DNA-induced CD8high T cell apoptosis in patients with systemic lupus erythematosus and rheumatoid arthritis.

ObjectiveTo investigate the potential role of hepatitis B virus (HBV) DNA-induced CD8high T cell apoptosis in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).MethodsThe activity and HBV seropositivity rates of patients with SLE and RA were determined. The proportions of T cell subgroups were detected by fluorescence-activated cell sorting. The apoptosis of T cell subgroups was detected after peripheral blood mononuclear cells were stimulated with HBV DNA.ResultsThe HBV infection rate was higher in patients with RA than in patients with SLE. Current or previous HBV infection was more common among patients with inactive SLE than among those with active SLE. Conversely, previous or current HBV infection was more common among patients with active RA than among those with inactive RA. CD4−CD8high T cell counts were higher among patients with active SLE than in those with inactive SLE. However, CD4−CD8high T cell counts were lower in patients with active RA patients than in those with inactive RA. HBV DNA increased the apoptosis of CD4−CD8high T cells.ConclusionHBV DNA-induced CD8high T cell apoptosis appears to play different roles in SLE and RA.

Tumor necrosis factor-alpha stimulated gene-6: A biomarker reflecting disease activity in rheumatoid arthritis.

BackgroundTo explore the serum tumor necrosis factor‐alpha stimulated gene‐6 (TSG‐6) level and its association with disease activity in rheumatoid arthritis (RA) patients.MethodsWe recruited 176 RA patients, 178 non‐RA patients (lupus erythematosus, osteoarthritis, ulcerative colitis, ankylosing spondylitis and psoriasis) and 71 healthy subjects. Serum TSG‐6 levels were detected by enzyme‐linked immunosorbent assay (ELISA). RA patients were divided into inactive RA and active RA groups by disease activity score of 28 joints based on C‐reactive protein (DAS28‐CRP). The receiver operating characteristic (ROC) curve and Spearman's rank correlation test analyzed the correlation between TSG‐6 concentration and RA disease activity.ResultsTumor necrosis factor‐alpha stimulated gene‐6 levels in the RA group were increased (p < 0.01). TSG‐6 concentrations indicated an upward tendency with increased disease activity; The area under the curve (AUC) of TSG‐6 for diagnosing RA and assessing the severity of RA were 0.78 and 0.80, respectively; The combination of TSG‐6 and anti‐mutated citrullinated vimentin antibodies (anti‐MCV) (sensitivity:98.4%)improved the diagnostic accuracy of RA. Binary logistic regression analysis showed that TSG‐6 was an independent risk factor related to the severity of RA, and OR (95% CI) was 1.2 (1.003–1.453).ConclusionThe TSG‐6 levels in RA patients were elevated and related to disease activity. Therefore, TSG‐6 may serve as a new potential biomarker for evaluating RA disease activity.

Association Between Blood PLT and RBC Related Indices and Disease Activity in Patients with Rheumatoid Arthritis.

BackgroundPlatelet (PLT) and red blood cell (RBC) have been demonstrated to play a critical role in inflammatory processes. This study aimed to evaluate the association of blood PLT and RBC related parameters with the disease activity in rheumatoid arthritis (RA) patients, and also to investigate the role of these indices in differentiating among RA patients with different disease activity.MethodsClinical data from RA patients were retrospectively analyzed. RA patients were divided into inactive group and active group according to DAS28-CRP. The relationship between blood PLT and RBC counts-related indices and DAS28-CRP was detected by Spearman correlation. ROC curve was used to assess the diagnostic value of these indices in differentiating active RA from inactive RA.ResultsActive RA patients exhibited higher level of PLT counts but significantly lower levels of RBC counts, hemoglobin (Hb), red blood cells-platelet ratio (RPR) and hemoglobin-platelet ratio (HPR) compared with inactive RA. PLT counts were positively but RBC counts, Hb, RPR and HPR were negatively related with DAS28-CRP.ConclusionBlood PLT and RBC related indices were significantly associated with RA disease activity. These indices may be used to distinguish active RA from inactive RA.

Upregulated miR-146a Expression in Peripheral Blood Relates to Th17 and Treg Imbalance in Elder Rheumatoid Arthritis Patients

Background: The expression level of microRNA-146a (miR-146a) increased in peripheral blood and synovialis tissue of rheumatoid arthritis (RA) patient, and it may play an important role in the pathological process of RA. We investigated its possibility as a diagnostic marker and the correlation with T helper 17 (Th17) and Treg cells in elder RA patients. Methods: Blood samples were collected from 38 active RA patients, 38 inactive RA patients, and 40 healthy controls. RNA expression levels of miR-146a were detected from the peripheral blood samples. The proportion of Th17 and Treg cells were analyzed, as well as their cell-specific transcription factor retinoic acid-related orphan receptor variant 2 (RORc) and forkhead box protein 3 (FOXP3). Furthermore, secretion of pre-inflammatory and anti-inflammatory factors was detected. Correlations between miR-146a and these factors were also analyzed. Results: Compared with healthy control, expression levels of miR-146a in inactive and active groups were significantly higher, with the highest level in active group. The expression of miR-146a and the RA severity, Th17 cell ratio, RORc expression, IL-17 level showed a significant positive correlation, while it showed a significantly negative correlation with Treg cell ration, FOXP3 expression, and TGF-β1 secretion. Conclusions: These results suggested that miR-146a may be used as a disease progression marker in the peripheral blood of elder RA patients.

Cardiovascular Autonomic Function Changes and Predictors During a 2-Year Physical Activity Program in Rheumatoid Arthritis: A PARA 2010 Substudy.

Background: Chronic inflammation leads to autonomic dysfunction, which may contribute to the increased risk of cardiovascular diseases (CVD) in patients with rheumatoid arthritis (RA). Exercise is known to restore autonomic nervous system (ANS) activity and particularly its parasympathetic component. A practical clinical tool to assess autonomic function, and in particular parasympathetic tone, is heart rate recovery (HRR). The aim of this substudy from the prospective PARA 2010 study was to determine changes in HRR post-maximal exercise electrocardiogram (ECG) after a 2-year physical activity program and to determine the main predictive factors associated with effects on HRR in RA.Methods: Twenty-five participants performed physiotherapist-guided aerobic and muscle-strengthening exercises for 1 year and were instructed to continue the unsupervised physical activity program autonomously in the next year. All participants were examined at baseline and at years 1 and 2 with a maximal exercise ECG on a cycle ergometer. HRR was measured at 1, 2, 3, 4, and 5 min following peak heart rate during exercise. Machine-learning algorithms with the elastic net linear regression models were performed to predict changes in HRR1 and HRR2 at 1 year and 2 years of the PARA program.Results: Mean age was 60 years, range of 41–73 years (88% women). Both HRR1 and HRR2 increased significantly from baseline to year 1 with guided physical activity and decreased significantly from year 1 to year 2 with unsupervised physical activity. Blood pressure response to exercise, low BMI, and muscular strength were the best predictors of HRR1/HRR2 increase during the first year and HRR1/HRR2 decrease during the second year of the PARA program.Conclusion: ANS activity in RA assessed by HRR was improved by guided physical activity, and machine learning allowed to identify predictors of the HRR response at the different time points. HRR could be a relevant marker of the effectiveness of physical activity recommended in patients with RA at high risk of CVD. Very inactive and/or high CVD risk RA patients may get substantial benefits from a physical activity program.

Association among B lymphocyte subset and rheumatoid arthritis in a Chinese population

Background and aimAutoantibody production are the main risk factors for inflammation of rheumatoid arthritis (RA). This study aimed to investigate differences in B lymphocyte subsets (native B, memory B, and plasmablasts) and several cytokines in RA patients and their correlation with the clinical parameters.MethodsIn total, 81 RA patients (active RA and inactive RA) and 40 healthy subjects were recruited between September 2018 and October 2020. The distribution of B lymphocyte subsets in peripheral blood samples was measured via flow cytometry and the plasma cytokines were detected by enzyme linked immunosorbent assay. The receiver operating characteristic curve (ROC) was used to evaluate the value of each index for RA diagnosis and activity prediction.ResultsThe percentages of native B and memory B cells in RA patients did not differ significantly from the percentages of those in healthy controls. However, the percentage of plasmablasts in active RA patients was significantly higher compared with healthy subjects and inactive RA patients. The percentage of plasmablasts was significantly related to C reaction protein. ROC curve analysis showed that when the best cutoff value of plasmablasts/B cell was 1.08%, the area under the curve (AUC) for diagnosing RA was 0.831 (95% CI 0.748 ~ 0.915), the specificity was 91.4%, and the sensitivity was 67.5%. The AUC predicted by the combination of plasmablast and anti-CCP for active RA patients was 0.760, which was higher than that of plasmablast and anti-CCP.ConclusionIn conclusion, the percentage of plasmablast varies among RA patients in different stages. The percentage of plasmablasts can be used as an early diagnosis marker for RA.

Neutrophil-lymphocyte, platelet-lymphocyte and lymphocyte-monocyte ratios may not be useful markers to assess disease activity in rheumatoid arthritis: A STROBE-compliant article.

The associations among the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR) and disease activity in rheumatoid arthritis remains unclear.To evaluate these indicators as potential markers of disease activity in patients with rheumatoid arthritis (RA).This cross-sectional study included 547 adult patients with RA. The patients were divided into two groups according to the disease activity score (DAS) system: remission and disease activity. Differences in the NLR, PLR and LMR of the two groups were assessed. Correlations were analyzed using Spearman analysis, and receiver operating characteristic (ROC) curves were used to identify the sensitivity, specificity, and optimal cutoff values to differentiate active RA patients from inactive RA patients.There was a statistically significant difference in the NLR (4.2 ± 3.2 vs 3.4 ± 2.4, P = .034) and PLR (222.3 ± 136.4 vs 176.9 ± 89.8, P = .006) between the two groups, but not for the LMR (3.0 ± 1.8 vs 3.4 ± 2.4, P = .115). In addition, the DAS28 and traditional inflammatory markers, including ESR and CRP, were weakly positively correlated with the NLR and PLR. Based on the ROC curves, the NLR (sensitivity 31.8%, specificity 77.8%) and PLR (sensitivity 57.3%, specificity 63.9%) were less valuable than the ESR (sensitivity 67.2%, specificity 91.7%) and CRP (sensitivity 76.2%, specificity 91.7%) for differentiating inactive RA patients from active RA patients due to low sensitivity and specificity and combining NLR or PLR also cannot significantly improved the diagnostic value of ESR and CRP.NLR, PLR and LMR may not be an useful independent diagnostic or complementary marker for disease activity in RA patients.