Active Rheumatoid Arthritis Group Research Articles

Exploring the Correlation between Interleukin-17A Promoter Polymorphism at its -197 G/A and Rheumatoid Arthritis: Impact on Disease Severity and Activity

T helper 17 (Th17) cells have been reported to be the most powerful factor in autoimmune disorder pathogenesis, which points to the Th17 master cytokine, interleukin (IL)-17A, as the crucial mediator. We aimed to determine the impact of IL-17A polymorphism in the -197 G/A promoter region on level of IL-17 and intensity of rheumatoid arthritis (RA) disease symptoms. This case-control study was conducted at the Department of Clinical Rheumatology of Aswan university Hospital and included 35 people suffering RA and 30 volunteer controls, matched for age and sex. Rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, erythrocyte sedimentation rate (ESR), serum IL-17, and C-reactive protein (CRP) were measured in the RA patient group. Restriction fragment length polymorphism (RFLP) was conducted by polymerase chain reaction (PCR) amplicon obtained by IL-17A -197 G /A primers. Of the 35 RA patients, RF was positive in 33 (94.29%) and anti-CCP antibodies in 25 (71.43%), CRP in 31 (88.57%). Of the 35 RA patients, 5 (14.29%) patients carried the G/G genotype, 18 (51.43%) G/A and 12 (34.29%) A/A. IL-17 serum level was significantly greater in the more active RA (DAS28 >5.1) group than the less active (DAS28 ≤5.1) group. Of the RA patients carrying wild type G/G genotype, 60% had more active disease (DAS 28> 5.1), as compared to those with lower activity (DAS 28 ≤5.1), 40% carried the wild type G/G genotype. In conclusion, the study findings imply that IL-17A gene polymorphism is connected to RA clinical severity rather than with RA susceptibility.

The relationship between disease activity with pan-immune-inflammatory value and systemic immune-inflammation index in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease. Immune system cells have an important role in RA. Our aim was to investigate the relationship between disease activity, systemic immune-inflammation index (SII), and pan-immune-inflammation value (PIV) levels in RA patients. We planned to investigate whether these 2 measurements have an advantage over each other. About 67 patients diagnosed with RA and 49 healthy controls included in this study. RA was diagnosed based on 2010 ACR classification criteria. In this cross-sectional study, peripheral blood tests, C-reactive protein (CRP), hemogram, and erythrocyte sedimentation rate levels were noted after the physical examination of all participants. PIV was calculated with the formula: (neutrophil count × platelet count × monocyte count) / lymphocyte count. SII was calculated as follows: (neutrophil count × monocytes count) / lymphocyte count. The disease activity score 28 (DAS28) were noted in patients with RA. CRP values of active RA group were significantly higher than remission RA and control groups (P < .001), control and remission RA groups were similar (P = .86). PIV and SII are significantly higher in active RA than remission RA and control (P < .001, P < .001) higher in remission RA than control (P < .001, P < .001). Receiver operating characteristic curve analysis in predicting remission compared to the control group, CRP was not significant, PIV and SII was significant and PIV has higher sensitivity and sensitivity, a PIV value of > 217.31 have sensitivity 75.0% and specificity 85.7%. CRP, PIV, and SII are statistically significant in predicting active RA compared to the remission RA and control group. Our findings show that PIV, and SII are easy, inexpensive and reliable markers predicting remission in RA patients. CRP was not significant compared to remission RA and control group, PIV and SII was significant and PIV has higher sensitivity and specificity than SII in the remission group in RA. Patients with high disease activity, PIV, SII, and CRP levels were effective in showing disease activity compared to RA remission group and healthy controls.

Hsa-miR-21-5p reflects synovitis and tenosynovitis components of Musculoskeletal Ultrasonography Seven-joint Scores in Rheumatoid Arthritis Disease and Predicts the Disease Flare

Rheumatoid arthritis (RA) is characterized by progressive joint destruction with subsequent serious disability. Objective biomarkers of RA course progression are lacking, which necessitates the discovery of activity indicators and predictors of the disease outcome. Musculoskeletal Ultrasound Seven-joint Score (MSUS7) is proposed as a reliable technique to evaluate radiographic RA progression. Homo sapiens-microRNA-21-5p (hsa-miR-21-5p) plays an important role during joint remodeling and the pro-inflammatory process driving RA progression. We aimed to evaluate plasma hsa-miR-21-5p as a noninvasive RA activity biomarker and to investigate if hsa-miR-21-5p is linked to MSUS7 components in the context of RA activity. This cross-sectional study included 71 RA patients classified into inactive (n = 36) and active (n = 35) groups according to the Disease Activity Score 28-joint count with ESR (DAS28-ESR). Joints were assessed by MSUS7. Gray-scale ultrasound (GSUS) and power Doppler ultrasound (PDUS) were used to rate the synovitis, tenosynovitis, and erosion in the joints. Plasma hsa-miR-21-5p expression was measured by real-time PCR. The absolute count of regulatory T cell (Treg) was calculated after Treg frequency was assessed by flow cytometry. Results: Hsa-miR-21 expression was significantly up-regulated in the active RA group with a median fold change of 51.6 in comparison to the inactive cases with a median fold change of 7.7 (p < 0.001). Hsa-miR-21-5p was positively correlated with DAS28-ESR, C reactive protein (CRP), and rheumatoid factor (r = 0.7, p < 0.001, r = 0. 0.6, p < 0.001, and r = 0.4, p = 0.002, respectively), while negatively correlated with Treg absolute count (r = -0.4, p < 0.001). Hsa-miR-21-5p levels were correlated with synovitis and tenosynovitis in GSUS (r = 0.4, p < 0.001, r = 0.3, p = 0.025, respectively) and in PDUS (r = 0.5, p < 0.001 and 0.4, p = 0.001, respectively). The hsa-miR-21-5p accurately distinguished RA activity [AUC 0.933, 94.3% sensitivity, and 86.1% specificity]. Logistic regression analysis revealed hsa-miR-21-5p as an independent predictor for RA flare (OR = 1.228, p = 0.004). Hsa-miR-21-5p was linked to synovitis and tenosynovitis components of the MSUS7. Up-regulated hsa-miR-21-5p can be utilized as a predictor for RA disease flare.

Pan-Immune-Inflammation Index as a Biomarker for Rheumatoid Arthritis Progression and Diagnosis.

Introduction Rheumatoid arthritis (RA) is a chronic autoimmune condition that causes systemic inflammation and affects multiple joints. It is characterized by joint warmth, swelling, pain, and the formation of invasive synovial tissue known as pannus, which contributes to cartilage and bone degradation.Pan-immune-inflammation value (PIV), a marker derived from complete blood count parameters, has shown promise in predicting prognosis in various cancer types and pediatric conditions associated with immune abnormalities. This study aims to explore the relationship between RA, characterized by chronic inflammation and immune system involvement, and PIV, potentially shedding light on novel insights into RA's clinical implications. Methods One hundred four participants, including 64 RA patients (both newly diagnosed and established cases) and 40 healthy controls, were included in the study. Exclusion criteria for RA patients included acute infection, cancer, diabetes, or chronic illness, while control participants were excluded for inflammatory disorders, active infection, diabetes, or malignancy. We assessed disease severity using Disease Activity Score 28 (DAS 28) and obtained complete blood count values, including neutrophil, lymphocyte, platelet, monocyte, and red cell distribution width. C-reactive peptide (CRP) and erythrocyte sedimentation rate were also added.Statistical analyses included correlation assessments, t-tests, Mann-Whitney U tests, and multivariate linear regression. A multiclass receiver operating characteristic analysis determined optimal PIV cut-off values for distinguishing control, remission, and active RA groups, with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and odds ratios calculated. Results This study comprised a cohort of 104 participants, with a median age of 43.5±17.5. The Remission group was significantly younger than the Control group (p=0.006)but not compared to the Active RA group (p=0.393). CRPlevels were significantly higher in the Active RA group (p<0.001). Neutrophil counts were highest in the Active RA group (p<0.001), as were monocyte counts. Lymphocyte counts were significantly lower in the Active RA group (p<0.001). There were no significant differences in sedimentation rate, hemoglobin, platelet count, and mean platelet volume. PIVwas significantly elevated in the Active RA group (p<0.001) and higher in the Remission group than in the Control group (p=0.001).A PIV value of 353.48 exhibited 71.4% sensitivity, 86.2% specificity, 86.2% PPV, 71.4% NPV, and 78.13% test accuracy for distinguishing active rheumatoid arthritis (p<0.001).A PIV value exceeding 353.48 substantially increased the likelihood of a patient belonging to the active rheumatoid arthritis group, with a 14.62-fold higher probability.Furthermore, the study explored the relationship between clinical and laboratory variables and disease activity in RA patients, finding significant differences inPIV among DAS groups (p=0.025). Conclusions The PIV offers a notable advantage as its constituent parameters are routinely assessed in rheumatoid arthritisand involve cost-effective and straightforward tests. We demonstrated that PIV serves as a valuable marker for distinguishing between remission and active RA when compared to healthy individuals. Additionally, it proved to be an effective tool for assessing disease activity in patients with active rheumatoid arthritis.

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.

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.

Glycerophospholipid metabolism is involved in rheumatoid arthritis pathogenesis by regulating the IL-6/JAK signaling pathway

To explore the metabolic mechanism of differential plasma interleukin (IL)-6 expression in patients with rheumatoid arthritis (RA). A total of 240 RA patients were enrolled in the non-target metabolomics study cohort and 69 healthy volunteers were included as healthy controls (HCs). Plasma IL-6 levels were detected by electrochemiluminescence assay. Plasma metabolites were detected by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Patients with active RA (n = 20) and remissive RA (n = 20) and 20 HCs were enrolled in the targeted validation cohort. Metabolites identified by non-target metabolomics were quantitatively analyzed by ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry. Effects of 1-oleoyl-sn-glycero-3-phosphocholine (OGPC) associated with IL-6 on MH7A cells were assessed. After 24-h or 48-h induction by TNF-α, the supernatants were collected for IL-6 quantification by enzyme-linked immunosorbent assay. Furthermore, Western blot was performed to investigate the relative JAK2 and p-JAK2 expressions. With an increasing IL-6 level, OGPC shown to be related to the glycerophospholipid metabolism pathway by Kyoto Encyclopedia of Genes and Genomes analysis displayed a significant decrease. In the validating RA cohort, the OGPC concentrations in remissive RA group and active RA group decreased compared with HC group. OGPC down-regulated IL-6 secretion and p-JAK2 expression in TNF-α-induced MH7A cells in vitro. In conclusion, glycerophospholipid metabolism is the main metabolic pathway associated with the differential IL-6 expression in RA patients. The down-regulated OGPC is a promoting factor for the increased IL-6 plasma level in RA patients, which further affects the downstream JAK signaling pathway.

High Dimensional Analyses of Circulating Immune Cells in Psoriatic Arthritis Detects Elevated Phosphorylated STAT3.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis, affecting up to 40% of patients with psoriasis. Constitutive expression by CD4+ T cells of an active form of STAT3, a signal transducer and transcription factor, has been shown to induce many of the major features of PsA in an animal model. We used high dimensional mass cytometry (CyTOF) to probe ex-vivo levels of phosphorylated STAT3 (pSTAT3) in circulating immune cell subpopulations from PsA patients during active and inactive states. We evaluated the frequency of 16 immune cell populations and the levels of the activated forms of STAT3 (pSTAT3) and, for comparison, STAT1 (pSTAT1) and Src (pSrc) in whole blood fixed shortly after collection. In addition to PsA patients, we studied active rheumatoid arthritis (RA) patients. Increased levels of pSTAT3 were found in all the CD4+ T cell subsets analyzed, specifically, Th1, Th2, Th17, T follicular helper (Tfh) and T regulatory (Treg) as well as in CD14+CD16- (classical) monocytes from active PsA patients compared to inactive patients. After correcting for body mass index (BMI), smoking and conventional disease modifying antirheumatic drugs (c-DMARDs), levels of pSTAT3 levels remained increased in Th1 and Tfh CD4+ T cells, and in CD14+CD16- monocytes from active patients compared to inactive patients. No differences between the patient groups were observed for pSTAT1 or pSrc. No differences were found between the active PsA and active RA groups after correction for multiple testing. During active PsA, circulating Th1 and Tfh CD4+ T cells, and CD14+CD16- monocytes expressing high levels of pSTAT3 may play a role in PsA pathophysiology, perhaps by migration to inflamed sites.

AB0277 ASSOCIATION BETWEEN INTRA-ERYTHROCYTE METHOTREXATE POLYGLUTAMATE CONCENTRATION AND CLINICAL RESPONSE IN RHEUMATOID ARTHRITIS IN PATIENTS TREATED WITH METHOTREXATE INJECTABLE SUBCUTANEOUSLY

Background:Methotrexate (MTX) is the first-line treatment for rheumatoid arthritis (RA). Due to its short half-life, blood MTX dosage is not performed in current practice. Erythrocyte MTX-polyglutamate (MTX-PG), which penetrates into the red blood cells, would be correlated with the area under the MTX curve and would be more accessible for dosing. When treatment is initiated, its concentration correlates with efficacy and therapeutic adherence.Objectives:To determine the interest of erythrocyte MTX-PG dosage in case of failure of 1st line MTX treatment.Methods:In this single-centre cross-sectional study, RA patients presenting for consultation at the Saint-Etienne University Hospital, with a stable dose of MTX for more than 3 months at least 15 mg/week subcutaneously with either clinical remission (DAS28&lt;2.6) or active disease (DAS28&gt;3.2) were included between July 2nd 2018 and May 28th 2020. In order to assess therapeutic compliance, the patient completed the compliance questionnaire of Rheumatology (CQR) questionnaire. The determination of erythrocytic MTX-PG was performed on a 5 mL blood sample by liquid chromatography method for the determination of the different PG forms.Results:Sixty patients were included, 34 in the active RA group and 26 in the RA group in remission. One patient withdrew his consent. Only 16% of patients were observed with a CQR score &gt; 80%. Patients in remission were leaner with a longer duration of disease and MTX treatment. The sex ratio, RA status, creatinine clearance and MTX dose was not different in both groups. The CQR was better in the remission group than in the active RA group. However, total MTX-PG was not different in the two groups. The same results were observed for the different forms of MTX-PG 1, 2, 3 or 4. In contrast, in the remission PR group, total MTX-PG or MTX-PG2, 3, 4 and 5 correlated inversely with BMI while MTX-PG3 correlated positively with BMI in the active PR group. In the active PR group, MTX-PG5 correlated with MTX dose.Conclusion:MTX-PG dosage is not a biomarker of good response to MTX in our study. However, compliance is a key factor to be considered in RA with active disease in adapting patient management.

Identifying and Validating Plasma Circulating Renin‐Angiotensin System Components as Reliable Biomarkers of Rheumatoid Arthritis

Objective The renin-angiotensin system (RAS) is an enzymatic cascade that controls the cardiovascular, renal, and adrenal functions responsible for maintaining arterial blood pressure and balancing body fluids and electrolytes. The RAS comprised of two opposing arms: i) classical arm, consists of Angiotensin (Ang) Converting Enzyme (ACE) /Ang II/ Ang II type 1 receptor (AT1R), which modulates a diverse range of biological effects, including vasoconstriction, vascular smooth muscle cell proliferation, and hypertrophy of heart vessel wall, ii) protective arm, consists of ACE2/Ang-(1-7)/Mas receptor (MasR), that acts as the counter regulatory within the RAS. Chronic imbalances of these two arms of the RAS leads to different pathophysiological conditions in renal, cardiovascular (CV), and central nervous systems. The urinary or plasma circulating level of ACE2 has been associated with different disease conditions such as renal, CV, and metabolic disorders. The plasma circulating level of ACE2 has been associated with different diseases. As a body's defense mechanism, the increased level of circulating ACE2 degrades Ang II and keeps its level within the normal range. Several studies links plasma or urinary ACE2 levels in patients with various disease. These patients exhibited reduced ACE2 activity and considerable high levels of circulating anti-ACE2 autoantibody, suggesting that an assessment of circulating ACE2, anti-ACE2, Ang II and Ang1-7 could provide a useful diagnostic biomarkers panel for patients with different inflammatory diseases. Methods This study was conducted based on an approved IRB and using twelve unidentifiable rheumatoid arthritis (RA) patients (five active and seven remission patients) samples, which were provided by the Institute of Arthritis Research. Diagnosis of RA was made using a RAPID3 questionnaire in tandem with comparing the measured amount of C-reactive protein and Vectra DA score. Levels of Ang-(1-7) and Ang II peptides were measured using liquid chromatography in tandem with mass spectrometry. Anti-ACE2 autoantibodies were measured using a previously-established ELISA method. Results The Mean ± SD results of the levels of Ang-(1-7) and Ang II peptides show that Ang-(1-7) level in the active RA group (1.29 ± 1.79) was significantly lower than in the remission RA group (7.62 ± 7.035). In contrast to Ang-(1-7), Ang II levels were significantly higher in the active RA patients (5.43 ± 4.05) when compared with the remission group (0.86 ± 0.43) (Fig.1). The mean ELISA score was significantly higher in the active RA patients (Fig.1) and was also correlated with Ang II levels in the active but not in the remission group (Fig. 2). These results suggest that anti-ACE2 antibody is associated with RA activity and intensity. Conclusion Our study suggests that estimation of the level of Ang-(1-7) and Ang II peptides in addition to assessing anti-ACE2 antibodies in patient's plasma can be considered as effective means of RA stage diagnosis. This approach also could be applied to other inflammatory conditions such as cardiovascular, renal and pulmonary diseases, diabetes and cancer.

Yoga improves mitochondrial health and reduces severity of autoimmune inflammatory arthritis: A randomized controlled trial

BackgroundOxidative stress (OS) and mitochondrial alterations have been implicated in the pathogenesis of rheumatoid arthritis (RA). Various environmental triggers like air pollutants, smoking, unhealthy social habits and sedentary lifestyle induce OS, which may compromise mitochondrial integrity. This trial was designed to explore the effect of 8-weeks yoga practice on mitochondrial health and disease severity in an active RA group compared with a usual-care control group. MethodsA total of 70 subjects were randomized into two groups: yoga group and non-yoga group. Mitochondrial health was assessed by calculation of mitochondrial DNA copy number (mtDNA-CN), OS markers, mitochondrial activity, mitochondrial membrane potential (ΔΨm), circadian rhythm markers and transcripts associated with mitochondrial integrity: AMPK, TIMP-1, KLOTHO, SIRT-1, and TFAM. Parameters of disease activity and disability quotient were also assessed by disease activity score – erythrocyte sedimentation rate (DAS28-ESR) and health assessment questionnaire-disability index (HAQ-DI), respectively. ResultsIn yoga group, there was a significant upregulation of mtDNA-CN, mitochondrial activity markers, ΔΨm, and transcripts that maintain mitochondrial integrity after 8-weeks of yoga. There was optimization of OS markers, and circadian rhythm markers post 8-weeks practice of yoga. Yoga group participants showed significant improvements in DAS28-ESR (p < 0.05) and HAQ-DI (p < 0.05) over the non-yoga group. ConclusionAdoption of yoga by RA patients holds the key to enhance mitochondrial health, improve circadian rhythm markers, OS marker regulation, upregulation of transcripts that maintain mitochondrial integrity, reduce disease activity and its associated consequences on health outcome and hence can be beneficial as an adjunct therapy.

Can Cytokines be used as an Activation Marker in Rheumatoid Arthritis?

The etiopathogenesis of Rheumatoid Arthritis (RA) is not clearly understood. However, the role of the cytokines play an important part in this mechanism. We aimed to bring a new approach to the concept of 'remission' in patients with RA. RA is a chronic, autoimmune, inflammatory disease that involves small joints in the form of symmetrical polyarthritis and progresses with exacerbations and remissions. Pain, swelling, tenderness and morning stiffness are typical of the joints involved. Although it is approached as primary joint disease, a wide variety of extra-articular involvements may also occur. It is an interesting pathophysiological process, the exact cause of which is still unknown, with many environmental, genetic and potentially undiscovered possible factors in a chaotic manner. In this cross-sectional study, sedimentation rate (ESR), C- Reactive protein (CRP), Tumor necrosis factor (TNF)-α, soluble-TNF-α receptor (TNF-R), Interleukin (IL)-1B and IL-10 were measured in three groups which were healthy volunteers, patients with RA in the active period, and patients with RA in remission. Disease activity score-28 (DAS-28) was calculated in active RA and RA in remission. This study included 20 healthy volunteers, 20 remission patients with RA and 20 active RA patients. Venous blood samples were collected from patients in both healthy and RA groups. RA group consisted 43 (71.6%) female and 17 (28.4%) male. Control group consisted 11 (55%) female and 9 (45%) male. TNF-R was significantly high only in the active group according to the healthy group (p=0.002). IL-10 was significantly high in active RA, according to RA in remission (p=0.03). DAS-28 was significantly high in active RA, according to RA in remission (p=0.001). In the active RA group, ESR and TNF-R had a positive correlation (r:0.442; p=0.048). In the active RA group, there was also a positive correlation between TNF-R and CRP (r:0.621; p=0,003). Both healthy and active RA group had significant positive correlation between ESR and CRP (r: 0.481; p=0.032 and r: 0,697; p=0,001 respectively). TNF-R can be the main pathophysiological factor and a marker showing activation. TNF-R can be very important in revealing the effect of TNF on the disease and the value of this effect in the treatment and ensuring the follow-up of the disease with CRP instead of ESR in activation.

Study of Factors Influencing Dry Eye in Rheumatoid Arthritis.

Purpose The present study investigated the relationship between dry eye and the disease activity in patients with rheumatoid arthritis (RA). Methods Patients with RA were divided by the Ocular Surface Disease Index (OSDI) into the symptomatic group (score ≥ 12) and the asymptomatic group (score < 12). By using the Disease Activity Score (DAS-28) questionnaire, they were divided into the active group (score > 2.6) and the stable group (score ≤ 2.6). In the control group, 20 healthy adults with matched sex and age were selected. RA patients and healthy adults were inspected for the tear film break time (TBUT), tear meniscus height (TMH), corneal fluorescein staining (CFS), meibomian scan (MS), meibomian gland secretion score (MSS), and eyelid margin assessment (EMS). Results The TBUT of the RA group was significantly less than that of the control group, while the CFS, MS, EMS, and MSS were higher. The TBUT of the symptomatic RA group was significantly less than that of the asymptomatic group, and the CFS was higher. In the active RA group, only the CFS was higher than that of the stable group, and there was no significant difference between the two groups for other parameters. Furthermore, there was no significant correlation between the course of RA and the dry eye (P > 0.05). Conclusion The rheumatoid activity does not necessarily lead to an aggravation of dry eye. Regardless of the duration, RA was not found to exhibit relation with the severity of dry eye. Translational Relevance. RA patients with disease active period cannot be ignored for the existence of dry eye, since patients with dry eye often lack the signs and symptoms.

OSTEOPROTEGERIN (OPG) AND SOLUBLE RECEPTOR ACTIVATOR OF NUCLEAR FACTOR KAPPA B LIGAND (S-RANKL) IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease that may result in debilitating joint deformities with destruction of bone and cartilage. Inflammation is still considered the pivotal inducer of both components of joint damage. A mechanism of bone destruction that could be dissociated from inflammation was proposed in which osteoclasts activation play a prominent role in bone resorption. RANKL and its natural decoy receptor, osteoprotegerin (OPG), play key roles in osteoclast activation. Objective: To evaluate osteoprotegrin (OPG) and soluble RANKL (s-RANKL) level in serum of rheumatoid arthritis patients, and to correlate their levels in serum to disease activity and radiological findings (bone loss). Patients and methods: Fifty five rheumatoid arthritis patients were included in the study. They were classified according to disease activity into 2 groups: The first group was active RA group, and the second was inactive RA group. In addition, RA group was classified according to bone erosions into 2 groups: The first group was RA group with bone erosions and the second group was RA group without bone erosions. The study included 25 healthy individuals of matched age and sex as a control group. All participants were exposed to complete clinical examination, radiological examination, and full laboratory evaluation including osteoclast activity markers (OPG/ RANKL ratio), inflammation markers (ESR, CRP and DAS-28 score), immunological markers (RF and anti-CCP), biochemical markers (calcium, phosphorus and alkaline phosphatase) and complete blood picture (CBC). Results: OPG/ RANKL ratio was significantly lower in RA group compared to control group. OPG/RANKL ratio was significantly lower in active RA group compared to inactive RA group. OPG/ RANKL ratio was significantly lower in RA group with bone erosion compared to RA group without bone erosions. OPG/ RANKL ratio showed significant negative correlation with both disease duration (in all RA groups) and inflammatory markers (in some not all RA groups). OPG/ RANKL ratio did not correlate with biochemical markers in all RA groups. Conclusion: OPG/ RANKL ratio could be used to monitor joint damage (bone erosions) progression in patients with RA. Progression of joint damage (bone erosions) due to osteoclast over activity could, at least in part, be dissociated from inflammation. Therefore, targeting OPG/ RANKL ratio may be effective in preventing bone damage in RA patients.

Lack of association between clinical and ultrasound measures of disease activity in rheumatoid arthritis remission.

Objectives:The objective of this study was to assess the prevalence of ultrasound (US) abnormalities and association with clinical parameters in rheumatoid arthritis (RA) clinical remission.Methods:Patients with established RA in clinical remission (DAS28-CRP < 2.4) taking conventional synthetic disease-modifying anti-rheumatic drugs were recruited as part of the Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study. In addition, patients from the Newcastle Early Arthritis Clinic (NEAC) with early active RA (DAS28-CRP > 2.4) or seronegative non-inflammatory arthralgia (NIA) were studied as positive and negative controls, respectively. The association between individual dependent variables (synovial power Doppler and greyscale, tenosynovial greyscale, and erosions) and clinical parameters was assessed by multivariate ordinal logistic regression, with adjustment for multiple testing.Results:A total of 294 patients were included: 66 RA in remission, 146 active RA, and 82 NIA. Within the active RA group, significant associations were observed between swollen joint count and higher total synovial greyscale score (OR 1.17 95% CI 1.08–1.26, p < 0.001) and higher total synovial power Doppler score (OR 1.20, 95% CI 1.12–1.30, p < 0.001). No significant associations were observed for the NIA group. In the RA remission group, US abnormalities were frequently observed and comparable for both DAS28-CRP and 2011 ACR/EULAR Boolean remission, with no significant association with clinical parameters identified.Conclusion:We observed widespread subclinical US findings in RA patients in clinical remission, even when remission is defined using the stringent ACR/EULAR Boolean criteria. In contrast to active disease, synovial power Doppler failed to show significant association with any of the clinical parameters in RA remission. Our results suggest that clinical and US examinations are non-overlapping in evaluating RA remission, challenging the proposition of US-driven management strategies in this setting.

Serum hepcidin level and rheumatoid arthritis disease activity.

ObjectiveThe present study aimed to determine the relationship between the serum hepcidin level and disease activity in patients with rheumatoid arthritis (RA).MethodsThis study was conducted on 80 patients with RA (36 cases with anemia of chronic disease [ACD] and 44 patients without ACD). Disease activity was measured by the 28-joint Disease Activity Score based on the erythrocyte sedimentation rate (DAS28-ESR). According to the DAS28-ESR score, 52 and 28 cases were categorized as inactive to moderately active RA (DAS28-ESR≤5.1) and highly active RA (DAS28-ESR>5.1), respectively. In addition, the serum hepcidin level was evaluated in all patients to determine its correlation with the DAS28-ESR score.ResultsThere was no significant difference between the RA with ACD and RA without ACD groups in terms of the median (interquartile range) hepcidin level (1207 [985.2] vs. 923.8 [677.3] ng/mL; P=0.57). Likewise, no significant difference was observed between the active RA and inactive to moderately active RA groups in this regard (1131.8 [991.3] vs. 1090.9 [631.4] ng/mL; P=0.53).ConclusionHepcidin has no association with disease activity in RA. Therefore, it is not necessary to measure hepcidin to determine the RA activity.

The importance of red cell distribution width and neutrophil-lymphocyte ratio as a new biomarker in rheumatoid arthritis

Objectives: Rheumatoid arthritis (RA) is a long-lasting autoimmune disorder that primarily affects the joints. Various biomarkers have been used for the prognosis and clinical follow-up. There are few studies that have investigated whether or not neutrophil-lymphocyte ratio (NLR) and red cell distribution width (RDW) are good indicators of systemic inflammation. The present study aims to explore the prognostic value of RDW and NLR in rheumatoid arthritis (RA) as a new inflammatory marker. Methods: RA patients (n = 124) who presented to the Rheumatology outpatient clinic in our hospital between March 2015 and May 2015 were included in this study retrospectively. As a first group, 47 clinically active RA patients who had high acute phase proteins were included. In the second group, 73 clinically in-remission RA patients who had normal acute phase proteins were included. Fifty-five healthy volunteers constituted the control group. Results: The mean RDW was found to be 15.2 ± 2.9 in the active group; 14.6 ± 2 in the inactive group and 13.4 ± 1.4 in the control group (p &amp;lt; 0.01). The mean NLR was found to be 3.7 ± 2.2 in the active group; 3.7 ± 1.6 in the inactive group and 3.2 ± 0.9 in the control group (p = 0.190). There were statistically significant differences between the RDW values of the active-period RA patients with the control group (p &amp;lt; 0.01). There was statistically significant difference between RDW values of active RA and inactive RA patients (p &amp;lt; 0.01). The NLR results between the RA group and the control group (p = 0.700); the active RA group, and the inactive RA group (p = 0.169) were similar. There was not statistically difference between the NLR values of active RA patients with the control group (p = 0.360). There was statistically difference between the NLR values of inactive RA patients with the control group (p = 0.047). Conclusion: RDW was found higher in all RA group than control, additionally was also higher in active RA group than remission group. NLR values of remission group was higher than control.

Vitamin D level in Rheumatoid arthritis and its correlation with the disease activity

Objective Vitamin D has an immunomodulatory and anti-inflammatory action, and its deficiency may cause several autoimmune disorders, including rheumatoid arthritis (RA). The relationship between vitamin D level and the severity of RA is of mere interest to several researchers. Patients and methods This prospective study included 40 cases of RA and 20 healthy controls, of age group between 40–70 years. Serum Vitamin D levels were measured and compared in RA patients and controls. Vitamin D levels in RA patients were measured in three different groups; active RA group, inactive RA group and control. Results Sixty-five percent patients of active RA were Vitamin D deficient versus only 40% of inactive RA patients. The serum Vitamin D levels were also significantly lower in the RA patients (mean value of 18.09 ± 8.99 ng/ml), as compared to the controls (mean value of 29.67 ± 11.34 ng/ml). There was an inverse significant correlation between serum Vitamin D levels and RA disease activity as measured by DAS28. The mean serum Vitamin D levels were 18.81 ± 6.679 ng/ml, 14.42 ± 6.856 ng/ml, 9.83 ± 6.791 ng/ml, in low disease activity, moderate disease activity, and high disease activity groups, respectively. Conclusion Vitamin D deficiency is more common in autoimmune diseases as RA and may be one of the leading cause of increased disease activity.

Association of MiRNA-146a, MiRNA-499, IRAK1 and PADI4 Polymorphisms with Rheumatoid Arthritis in Egyptian Population

Background/Aims: Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting up to 1% of the population worldwide. The aim of the present study was to investigate whether miRNA-146a rs2910164, miRNA-499 rs3746444, IRAK1 rs3027898 and PADI4 rs1748033 polymorphisms are associated with susceptibility to RA in Egyptians and whether they influence disease severity and activity. Methods: The study was performed on 104 unrelated RA patients and 112 healthy subjects. RA patients were further subdivided into active and inactive RA groups. Polymorphisms were genotyped by using real-time polymerase chain reaction with TaqMan allelic discrimination assay. Results: Significant differences in the frequency of miRNA-146a rs2910164, miRNA-499 rs3746444, IRAK1 rs3027898 and PADI4 rs1748033 alleles and genotypes were observed between RA patients and controls. Only CA and AA genotypes of IRAK1 rs3027898 shows a significant difference between active and inactive subgroups. MiRNA-146a rs2910164 and IRAK1 rs3027898 polymorphisms were a risk factor for predisposition to RA in codominant and dominant tested inheritance models, while, the miRNA-499 rs3746444 and PADI4 rs1748033 polymorphisms were a risk factor in codominant and recessive one. CG and GG genotypes of miRNA-146a rs2910164 were associated with positive erosions. CA genotype of IRAK1 rs3027898 was associated with low disease activity and negative erosions, while, the AA genotype was associated with high disease activity. CC genotype of PADI4 rs1748033 was associated with negative rheumatoid factor. Conclusion: The 4 studied SNPs were likely to play an important role in the susceptibility to RA and can influence disease severity and activity in Egyptian population.

A novel ultrasound-based technique to establish a correlation between disease activity and local carotid stiffness parameters in rheumatoid arthritis.

Cardiovascular (CV) disease is the reason for most mortality cases in RA and cannot be explained only by the presenceof traditional CV risk factors. In this study, we aimed to investigate the relationship between local carotid stiffness (CS)parameters measured by a novel ultrasound method and inflammatory disease activity in rheumatoid arthritis (RA) patients.Material and methods: The study was conducted with 70 RA patients and 35 control subjects. According to their disease activityscore (DAS-28), the RA patients were classified into active RA (n = 36; DAS-28 > 3.2) and inactive RA (n = 34; DAS-28≤ 3.2) groups. A novel non-invasive echo-tracking system was used to measure carotid intima-media thickness (C-IMT), diameter,pulsatile strain, distensibility, and carotid pulse wave velocity (PWV) on 128 sites of the common carotid artery. Erythrocytesedimentation rate (ESR) and C-reactive protein (CRP) levels were also determined. Carotid PWV and IMTwere significantly higher in the active RA patients (8.20±1.47 m/s and 6.88±1.50 mm, respectively) compared to the inactivegroup (6.06±1.21 mm and 7.32±1.19 m/s, respectively) and the control subjects (0.68±0.12 mm and 6.41±0.98, respectively).In all RA patients, a statistically significant correlation was found between carotid PWV and age (r=0.435, p<0.001), ESR(r=0.257, p=0.033), and DAS-28 (r=0.314, p=0.009). According to the multivariate logistic regression analysis, age, DAS-28,and ESR were independent predictors of CS. A strong correlation was found between disease activity and localCS parameters in patients with RA. We also demonstrated that both active and inactive RA patients showed increased PWVvalues compared with the control subjects. This easily applicable and previously confirmed method can be used in future toassess cardiovascular risk in broad study populations from different risk groups.