Rheumatoid Arthritis Disease Activity Research Articles

MicroRNA-143-3p ameliorates collagen-induced arthritis by polarizing naive CD4+ T cells into Treg cells.

Rheumatoid arthritis (RA) is a persistent and systemic autoimmunity disease. The abnormal differentiation of Treg cells is important in pathogenesis. Despite previous studies showed that microRNAs (miRNAs, miR) are pivotal modulators of Treg cells, the effect of miRNAs on Treg cell differentiation and function is not clear. Our study wants to reveal the relationship of miR-143-3p with the differentiative ability and biofunction of Treg cells during the development of RA. The Expressing level of miR-143-3p and cell factor generation in peripheral blood (PB) of RA sufferers were identified by ELISA or RT-qPCR. The roles of miR-143-3p in Treg cell differentiation were studied via ShRNA/lentivirus transfection. Male DBA/1J mice were separated into control, model, control mimics, and miR-143-3p mimics groups to analyze the anti-arthritis efficacy, the differentiative ability of Treg cells, and the expression level of miR-143-3p. Our team discovered that the Expressing level of miR-143-3p was related to RA disease activities in a negative manner, and remarkably related to antiinflammation cell factor IL-10. In vitro, the expression of miR-143-3p in the CD4+ T cells upregulated the percentage of CD4+ CD25+ Fxop3+ cells (Tregs) and forkhead box protein 3 (Foxp3) mRNA expression. Evidently, miR-143-3p mimic intervention considerably upregulated the content of Treg cells in vivo, validly avoided CIA progression, and remarkably suppressed the inflammatory events of joints in mice. Our findings indicated that miR-143-3p could ameliorate CIA through polarizing naive CD4+ T cells into Treg cells, which may be a novel strategy to treat autoimmune diseases such as RA.

Efficacy and Safety of Tofacitinib in Patients with Rheumatoid Arthritis

Objective: The aim of our study is to show the efficacy and side effects of tofacitinib in patients with rheumatoid arthritis (RA). Methods: 66 Patients who were followed up in the rheumatology outpatient clinic, were older than 18 years, and used tofacitinib for at least three months were included. Blood count, liver transaminase levels, cholesterol and triglyceride levels, C-reactive protein (CRP) levels, and erythrocyte sedimentation rate (ESR) were determined before and at the third and sixth months of the tofacitinib treatment. Before and after treatment, DAS 28-ESR, morning stiffness duration, and VAS score were also calculated Results: The mean age was 54.7±12.0 years, and 84.8% were women. The mean duration of tofacitinib use was 19.0±13.5 months. Duration of morning stiffness, VAS and DAS 28-ESR scores decreased significantly after tofacitinib (p<0.001). The leukocyte count after treatment also decreased significantly compared to before treatment. Side effects related to tofacitinib were seen in 33.3% of the patients. Rash, cough, and nausea were the most common side effects. Tofacitinib-associated Herpes Zoster infections were seen in 13.6% of the patients. Tofacitinib treatment was discontinued in 48.5% of patients due to adverse effects, drug ineffectiveness, and disease activation. Conclusion: There was statistically significant decrease in RA disease activity with tofacitinib treatment. It was noteworthy that 33.3% of the patients developed adverse effects and 48.5% developed a condition requiring discontinuation of tofacitinib treatment.

68Ga-FAPI PET/CT for Rheumatoid Arthritis: A Prospective Study.

Background In rheumatoid arthritis (RA), fibroblast-like synoviocyte cells, which are involved in inflammation of the articular cartilage and bone, overexpress fibroblast activation protein (FAP). This is a feature that could be leveraged to improve imaging assessment of disease. Purpose To determine the performance of gallium 68 (68Ga)-labeled FAP inhibitor (FAPI) in assessing joint disease activity of RA and to compare with fluorine 18 (18F) fluorodeoxyglucose (FDG) imaging. Materials and Methods Twenty participants with RA (15 women; mean age, 55 years ± 10 [SD]) were prospectively enrolled from September 2020 to December 2021 and underwent clinical and laboratory assessment of disease activity and dual-tracer PET/CT (68Ga-FAPI and 18F-FDG) imaging. Imaging-derived variables of PET joint count (the number of joints positive for RA at PET) and PET articular index (a sum of the points of the joints using a three-point scale) were correlated to clinical and laboratory variables of disease activity. Results The combined output of both PET/CT techniques helped detect 244 affected joints, all of which showed positive results at 68Ga-FAPI PET/CT. However, fifteen of 244 (6.1%) FAPI-avid joints in six of 20 (30%) participants were not detected at 18F-FDG PET/CT. The maximum standardized uptake value of the most affected joint in each participant was higher in 68Ga-FAPI than in 18F-FDG PET/CT (9.54 ± 4.92 vs 5.85 ± 2.81, respectively; P = .001). The maximum standardized uptake values of the joints at both 68Ga-FAPI and 18F-FDG PET/CT were positively correlated with laboratory evaluation of C-reactive protein levels (r = 0.49 [P = .03] and 0.54 [P = .01], respectively). The PET joint count and PET articular index scores at 68Ga-FAPI PET/CT were also positively correlated with most clinical disease activity variables and radiographic progression of joint damage (P < .05). Conclusion In participants with rheumatoid arthritis who underwent gallium 68 fibroblast activation protein inhibitor PET/CT, the extent of joint involvement correlated with clinical and laboratory variables of disease activity and showed a greater amount and degree of affected joints than at fluorine 18 fluorodeoxyglucose PET/CT. Clinical trial registration no. NCT04514614 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Williams and Ahlman in this issue.

Moringa Oleifera Extract Decreases Interleukin 6 Levels and Disease Activity in Rheumatoid Arthritis Patients

Moringa oleifera (MO) has anti-inflammatory, anti-arthritis, and immunosuppressant effects in Rheumatoid Arthritis (RA). This study aims to determine the effect of moringa oleifera extract on interleukin 6 levels and disease activity in RA. This research, with 30 patients, was divided into two groups: the intervention and the placebo. The intervention group received 40.50 mg/kg BW/day of Moringa oleifera extract for one month. IL-6 levels and SDAI scores were measured before and after the treatment. Paired t-test showed that IL-6 levels (p=0.070) and SDAI Scores (p=0.142) before and after MO administration for the control group were not significantly different (p&gt; 0.05). Paired t-test IL-6 (p=0.001) and SDAI Scores (p=0.001) before and after giving MO to the treatment group decreased significantly (p &lt;0.05). Independent t-test shows that the two changes, Delta-IL6 (p=0,008) and Delta-SDAI (p=0,017), are significantly different (p&lt;0.05). Moringa Oleifera Extract decreases IL-6 Levels and SDAI Scores in RA PatientsInternational Journal of Human and Health Sciences Vol. 07 No. 02 April’23 Page: 122-127

Seluang Fish (Rasbora sp.) Oil Improves Interleukin-17 Levels and Disease Activity in Rheumatoid Arthritis

BACKGROUND: Vitamin D has a role in downregulating the proinflammatory cytokines as well as promoting the antiinflammatory pathway in rheumatoid arthritis (RA). Seluang fish (Rasbora sp.) has potency as a new source of vitamin D. Previous study had proven Seluang fish oil efficacy in systemic lupus erythematosus. However, there are no trials that prove its efficacy in RA yet. Hence, this study was conducted to find out the ability of Seluang fish oil to improve proinflammatory cytokines, vitamin D levels, and disease activity in RA.METHODS: A clinical trial with a randomized and double-blind method was done in two groups, each one consisting of 17 RA subjects. One group was given 500 mL of a Seluang fish oil capsule (contains 665 IU cholecalciferol), while the other group was given a placebo daily, for 12 consecutive weeks. Measurements of the RA disease activity score 28 erythrocyte sedimentation rate (DAS28-ESR) and DAS28 C-reactive protein (DAS28-CRP), as well as measurement of interleukin (IL)-6, IL-17, and vitamin D levels by using immunoassay method were performed before and after the supplementation.RESULTS: Significant alterations in the lower levels of IL-17 were observed in the Seluang fish oil group (p=0.031), but not in the placebo group (p=0.320). Reduction of DAS28-ESR (p=0.000) and DAS28-CRP (p=0.000) score demonstrated that the Seluang fish oil supplementation was useful in reducing RA disease activity. No significant shift was observed in either vitamin D (p=0.967) or IL-6 levels (p=0.076) after Seluang Fish Oil supplementation.CONCLUSION: Seluang fish oil is effective in lowering IL-17 levels, DAS28-ESR, and DAS28-CRP, but not in improving vitamin D level or lowering IL-6 level in RA patients.KEYWORDS: rheumatoid arthritis, seluang fish oil, interleukin-6, interleukin-17, vitamin D, DAS28

Effects of Microecological Regulators on Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Randomized, Controlled Trials.

In this study, the available data from published randomized, controlled trials (RCTs) of the use of intestinal microecological regulators as adjuvant therapies to relieve the disease activity of rheumatoid arthritis (RA) are systematically compared. An English literature search was performed using PubMed, Embase, Scopus, Web of Science and the Cochrane Central Registry of Controlled Trials and supplemented by hand searching reference lists. Three independent reviewers screened and assessed the quality of the studies. Among the 2355 citations identified, 12 RCTs were included. All data were pooled using a mean difference (MD) with a 95% CI. The disease activity score (DAS) showed a significant improvement following microecological regulators treatment (MD (95% CI) of -1.01 (-1.81, -0.2)). A borderline significant reduction in the health assessment questionnaire (HAQ) scores was observed (MD (95% CI) of -0.11 (-0.21, -0.02)). We also confirmed the known effects of probiotics on inflammatory parameters such as the C-reactive protein (CRP) (MD -1.78 (95% CI -2.90, -0.66)) and L-1β (MD -7.26 (95% CI -13.03, -1.50)). No significant impact on visual analogue scale (VAS) of pain and erythrocyte sedimentation rate (ESR) reduction was observed. Intestinal microecological regulators supplementation could decrease RA activity with a significant effect on DAS28, HAQ and inflammatory cytokines. Nevertheless, these findings need further confirmation in large clinical studies with greater consideration of the confounding variables of age, disease duration, and individual medication regimens.

Geographic Variation in Disease Burden and Mismatch in Care of Patients With Rheumatoid Arthritis in the United States.

Our objective was to evaluate the factors associated with regional variation of rheumatoid arthritis (RA) disease burden in the US. In a retrospective cohort analysis of Rheumatology Informatics System for Effectiveness (RISE) registry data, seropositivity, RA disease activity (Clinical Disease Activity Index [CDAI], Routine Assessment of Patient Index Data-version 3 [RAPID3]), socioeconomic status (SES), geographic region, health insurance type, and comorbidity burden were recorded. An Area Deprivation Index score of more than 80 defined low SES. Median travel distance to practice sites' zip codes was calculated. Linear regression was used to analyze associations between RA disease activity and comorbidity adjusting for age, sex, geographic region, race, and insurance type. Enrollment data for 184,722 patients with RA from 182 RISE sites were analyzed. Disease activity was higher in African American patients, in those from Southern regions, and in those with Medicaid or Medicare coverage. Greater comorbidity was prevalent in patients in the South and those with Medicare or Medicaid coverage. There was moderate correlation between comorbidity and disease activity (Pearson coefficient: RAPID3 0.28, CDAI 0.15). High-deprivation areas were mainly in the South. Less than 10% of all participating practices cared for more than 50% of all Medicaid recipients. Patients living more than 200 miles away from specialist care were located mainly in Southern and Western regions. A disproportionately large portion of socially deprived, high comorbidity, and Medicaid-covered patients with RA were cared for by a minority of rheumatology practices. Studies are needed in high-deprivation areas to establish more equitable distribution of specialty care for patients with RA.

Development and validation of an ama instrument for assessing the disease activity on the basis of constitutional features in Amavata (Rheumatoid Arthritis)

BackgroundRheumatoid Arthritis (RA), having a striking clinical resemblance to amavata in traditional Indian medicine (Ayurveda) presents an opportunity to look at disease from two different healthcare perspectives. This differential information may potentially supplement one system with the knowledge of the other for optimal application. This study is the first of its kind, where Ayurvedic concepts of amavata have been adopted to enhance the knowledge about RA where optimal care is still beyond the common reach. ObjectiveThe study was conducted to develop and validate a novel ama score based upon constitutional features of ama as depicted in ayurvedic literature as a disease activity indicator in RA. Material and methodsThe study was conducted in two parts comprising development and textual validation of the ama assessment instrument (AAI) followed by its clinical testing. AAI comprising ten items, was developed where each item was provided with a range of scores to offer the assessment close to the patient's observations. The score obtained through AAI was clinically and statistically tested on 79 RA/amavata patients randomly selected for validity and reliability. The score obtained through AAI was tested for its correlation with the DAS-28 score and ESR. ResultsAma Assessment Instrument could find a slight correlation with acute phase reactant ESR (r-value between ESR and AMA at baseline is 0.287, and at 1st, 2nd, and 3rd follow-up is 0.276, 0.276 and 0.160 respectively) and DAS-28 (The r value between DAS and AMA at baseline is 0.231, and at 1st, 2nd and 3rd follow up is 0.218, 0.201 and 0.247 respectively). It however emerged as an independent disease status marker since it could mark the changes in the study population on a time scale more precisely as compared to DAS -28 or ESR. When the ama values at different follow-ups were compared, a significant difference was observed consistent with disease activity marker catching constitutional and GI related domain of the patients. When reducing values of ama score were compared to overall improvements as reported by the patients, a similar trend was observed showing that a change in ama score is reflective of a change in disease status and the impact of the disease on the patient. ConclusionThis study provided a quantitative measure for the abstract concept of ama which could be used to mark the disease activity in amavata or RA. The change in ama based scores can be used to assess disease status and the intervention related benefits. The observations prompt for the possible inclusion of AAI in RA composite score to make it more dynamic in terms of disease activity identification in RA.

Sequencing technology as a major impetus in the advancement of studies into rheumatism: A bibliometric study.

Rheumatism covers a wide range of diseases with complex clinical manifestations and places a tremendous burden on humans. For many years, our understanding of rheumatism was seriously hindered by technology constraints. However, the increasing application and rapid advancement of sequencing technology in the past decades have enabled us to study rheumatism with greater accuracy and in more depth. Sequencing technology has made huge contributions to the field and is now an indispensable component and powerful tool in the study of rheumatism. Articles on sequencing and rheumatism, published from 1 January 2000 to 25 April 2022, were retrieved from the Web of Science™ (Clarivate™, Philadelphia, PA, USA) database. Bibliometrix, the open-source tool, was used for the analysis of publication years, countries, authors, sources, citations, keywords, and co-words. The 1,374 articles retrieved came from 62 countries and 350 institutions, with a general increase in article numbers during the last 22 years. The leading countries in terms of publication numbers and active cooperation with other countries were the USA and China. The most prolific authors and most popular documents were identified to establish the historiography of the field. Popular and emerging research topics were assessed by keywords and co-occurrence analysis. Immunological and pathological process in rheumatism, classification, risks and susceptibility, and biomarkers for diagnosis were among the hottest themes for research. Sequencing technology has been widely applied in the study of rheumatism and propells research in the area of discovering novel biomarkers, related gene patterns and physiopathology. We suggest that further efforts be made to advance the study of genetic patterns related to rheumatic susceptibility, pathogenesis, classification and disease activity, and novel biomarkers.

Cost-effectiveness Analysis of Reference Infliximab (Remicade) Compared to its Biosimilar (Remsima) in Iraqi Patients with Rheumatoid Arthritis (Conference Paper )#

The study objective was to conduct Pharmacoeconomics study (cost-effective analysis) between infliximab reference (Remicade) and its biosimilar (Remsima) in patients with rheumatoid arthritis (RA) in Iraqi hospitals.&#x0D; This is a retrospective multicenter pharmacoeconomic analysis conducted at two large teaching governmental hospitals in Baghdad, Iraq which provided infliximab to patients with RA. Data were collected from patient’s medical records and face-to-face interviews with the patients from December 2021 to April 2022.&#x0D; The study included 57 patients with rheumatoid arthritis (RA). The patients were categorized into two groups according to the type of infliximab they received over 30 weeks: 27 patients received reference infliximab (Remicade) and 30 patients received biosimilar infliximab (Remsima). The two groups had comparable demographic and baseline disease parameters, with a mean age of 49.6 years and a BMI of 30.0. The vast majority of participants were women (82.5%) with low level of formal education (65%). Overall, both infliximab biopharmaceuticals had good effectiveness to reduce the RA disease activity (CDAI) and improve patient quality of life. They both had comparable adverse reactions including UTI, fatigue, and headache. There was no significant difference (P-value &gt;0.05) in disease activity between the two groups according to RA clinical disease activity index (CDAI) score across all three-time measures: before biological therapy, 14 weeks post-therapy and 30 weeks post-therapy.&#x0D; In 2019, Remicade was slightly more effective and provide better quality of life, but costlier ($41,896 per QALY) compared to Remsima. It was not clear whether the reference biologic (Remicade) or its biosimilar (Remsima) was more cost effective. In 2021, Remicade was more cost effective compared to Remsima because Remicade was less expensive and relatively more effective according to CDAI and EQ-5D-5L scores. Registering and purchasing both reference infliximab and its biosimilar was good idea to keep the competition in the price and maintain infliximab for RA patients.

Olive Oil and Nuts in Rheumatoid Arthritis Disease Activity.

Few observational studies investigated the relationship between single food groups and disease activity in rheumatoid arthritis (RA). Within a recent Italian cross-sectional study (365 patients, median age: 58.46 years, 78.63% females), we focused on two food groups, olive oil and nuts, representing vegetable sources of fatty acids. Disease activity was measured with Disease Activity Score on 28 joints based on C-reactive protein (DAS28-CRP) and the Simplified Disease Activity Index (SDAI). Robust linear and logistic regression models included tertile-based consumption categories of each food group and several confounders. Stratified analyses were performed by disease severity or duration. Higher consumption of both food groups exerted a favorable effect on disease activity, significant only for olive oil (Beta: -0.33, p-value: 0.03) in the linear regression on the overall sample. This favorable effect was stronger in the more severe or long-standing forms of RA (p-value for heterogeneity <0.05, especially for disease severity). Significant ORs were as low as ~0.30 for both food groups, strata (i.e., more severe and long-standing RA), and disease activity measures. Mean DAS28-CRP significantly decreased by ~0.70 for olive oil and ~0.55 for nuts in the two strata; mean SDAI significantly decreased by 3.30 or more for olive oil in the two strata. Globally, the beta coefficients doubled, and the ORs halved (in absolute values) for both food groups, reaching significance in 12 of the 16 available models fitted to the more severe or long-standing RA strata. More compromised forms of RA may benefit from increasing consumption of olive oil, olives, and nuts.

Profiling the peripheral immune response to ex vivo TNF stimulation in untreated juvenile idiopathic arthritis using single cell RNA sequencing

BackgroundJuvenile Idiopathic Arthritis (JIA) is an autoimmune disease with a heterogenous clinical presentation and unpredictable response to available therapies. This personalized transcriptomics study sought proof-of-concept for single-cell RNA sequencing to characterize patient-specific immune profiles.MethodsWhole blood samples from six untreated children, newly diagnosed with JIA, and two healthy controls were cultured for 24 h with or without ex vivo TNF stimulation and subjected to scRNAseq to examine cellular populations and transcript expression in PBMCs. A novel analytical pipeline, scPool, was developed wherein cells are first pooled into pseudocells prior to expression analysis, facilitating variance partitioning of the effects of TNF stimulus, JIA disease status, and individual donor.ResultsSeventeen robust immune cell-types were identified, the abundance of which was significantly affected by TNF stimulus, which resulted in notable elevation of memory CD8 + T-cells and NK56 cells, but down-regulation of naïve B-cell proportions. Memory CD8 + and CD4 + T-cells were also both reduced in the JIA cases relative to two controls. Significant differential expression responses to TNF stimulus were also characterized, with monocytes showing more transcriptional shifts than T-lymphocyte subsets, while the B-cell response was more limited. We also show that donor variability exceeds the small degree of possible intrinsic differentiation between JIA and control profiles. An incidental finding of interest was association of HLA-DQA2 and HLA-DRB5 expression with JIA status.ConclusionsThese results support the development of personalized immune-profiling combined with ex-vivo immune stimulation for evaluation of patient-specific modes of immune cell activity in autoimmune rheumatic disease.

Hypermethylation of Smad7 in CD4+ T cells is associated with the disease activity of rheumatoid arthritis.

Smad7 is protective in a mouse model of rheumatoid arthritis. Here we investigated whether Smad7-expressing CD4+ T cells and the methylation of Smad7 gene in CD4+ T cells contribute to the disease activity of RA in patients. Peripheral CD4+ T cells were collected from 35 healthy controls and 57 RA patients. Smad7 expression by CD4+ T cells were determined and correlated with the clinical parameters of RA including RA score and serum levels of IL-6, CRP, ESR, DAS28-CRP, DAS28-ESR, Swollen joints and Tender joints. Bisulfite sequencing (BSP-seq) was used to determine the DNA methylation in Smad7 promoter (-1000 to +2000) region in CD4+ T cells. In addition, a DNA methylation inhibitor, 5-Azacytidine (5-AzaC), was added to CD4+ T cells to examine the possible role of Smad7 methylation in CD4+ T cell differentiation and functional activity. Compared to the heath controls, Smad7 expression was significantly decreased in CD4+ T cells from RA patients and inversely correlated with the RA activity score and serum levels of IL-6 and CRP. Importantly, loss of Smad7 in CD4+ T cell was associated with the alteration of Th17/Treg balance by increasing Th17 over the Treg population. BSP-seq detected that DNA hypermethylation occurred in the Smad7 promoter region of CD4+ T cells obtained from RA patients. Mechanistically, we found that the DNA hypermethylation in the Smad7 promoter of CD4+ T cells was associated with decreased Smad7 expression in RA patients. This was associated with overreactive DNA methyltransferase (DMNT1) and downregulation of the methyl-CpG binding domain proteins (MBD4). Inhibition of DNA methylation by treating CD4+ T cells from RA patients with 5-AzaC significantly increased Smad7 mRNA expression along with the increased MBD4 but reduced DNMT1 expression, which was associated with the rebalance in the Th17/Treg response. DNA hypermethylation at the Smad7 promoter regions may cause a loss of Smad7 in CD4+ T cells of RA patients, which may contribute to the RA activity by disrupting the Th17/Treg balance.

Serum leptin level in rheumatoid arthritis and its relationship with disease activity

Objectives: To evaluate serum leptin levels in rheumatoid arthritis (RA) patients and to investigate its correlation with parameters of disease activity including DAS-28, C- reactive protein (CRP) and ESR.&#x0D; Materials and Methods: This study included 60 rheumatoid arthritis patients attended Ibn-Sina and Al-Salam Teaching Hospitals during the period from December 2013 to June 2014. The study also included 30 apparently healthy individuals as a control group who were age, gender, and merely body mass index matched to rheumatoid arthritis patients. Full clinical assessment of the patients was conducted by consultant rheumatologists/physicians. A Questionnaire Form was completed and DAS-28 was calculated. Five milliliters of blood were collected from patients and controls, then centrifuged and the serum was separated and frozen as aliquots at -20 co until use. The sera were tested by enzyme linked immune-sorbent assay ( ELISA) for leptin.&#x0D; Results: Serum leptin levels in RA patients in comparison to the control group were within normal range. Its value varied ranging between 0.7 to 7.5 ng/ml (in patients), and mean ± stander deviation in RA patients 2.1 ± 4.2 and in controls 3.13 ± 2.30. In RA patients, there was no correlations between serum leptin levels and DAS-28, CRP, ESR. Serum leptin levels positively correlated with body mass index (BMI) in both patient and control groups.&#x0D; Conclusions: Circulating leptin level does not seem to reflect disease activity in rheumatoid arthritis since there is no correlation between its serum levels and parameters of disease activity namely DAS -28, CRP, ESR.

Vitamin D Deficiency in Saudi Patients With Rheumatoid Arthritis.

Background Epidemiological studies indicate that vitamin D deficiency may increase the risk of developing autoimmune and chronic diseases such as rheumatoid arthritis (RA)and, therefore, is prevalent in patients with RA. Additionally, vitamin D insufficiency is associated with significant disease activity in patients with RA. This study aimed to assess the prevalence of vitamin D deficiency in Saudi patients with RA and determine whether there is an association between low vitamin D levels and RA disease activity. Methodology This cross-sectional retrospective study was conducted from October 2022 to November 2022 on patients who attended the rheumatology clinic at King Salman bin Abdulaziz Medical City, Medina, Saudi Arabia. Patients aged ≥18 years, diagnosed with RA, and not on vitamin D supplements were included. Demographic, clinical, and laboratory data were collected. Disease activity was measured using the disease activity score index of a 28-joint count using the erythrocyte sedimentation rate (DAS28-ESR). Results In total, 103 patients were included, with 79 patients being women (76.7%) and 24 being men (23.3%). The vitamin D level ranged from 5.13 to 94 ng/mL, with a median of 24. Of the studied cases, 42.7% had insufficient vitamin D levels, 22.3% had a deficiency, and 15.5% had severe deficiency. There were statistically significant correlations between the median vitamin D level and C-reactive protein (CRP), the number of swollen joints, and DAS. A lower median vitamin D level was detected among cases with positive CRP, swollen joints >5, and higher disease activity. Conclusions Patients with RA in Saudi Arabia were more likely to have low vitamin D levels. Moreover, vitamin D deficiency was linked to disease activity.Therefore, the measurement of vitamin D levels in patients with RA is essential, and vitamin D supplements might be important to improve disease outcomes and prognoses.

Racial and Ethnic Differences in a Biochemical Marker of Rheumatoid Arthritis Disease Activity.

Racial and ethnic disparities in rheumatoid arthritis (RA) disease activity measures have been documented. We compared racial and ethnic differences in disease activity using multiple composite measures, including an objective measure, the multi-biochemical disease activity (MBDA) score. Data are derived from the University of California, San Francisco RA Cohort, a longitudinal observational cohort. Participants with at least one MBDA measure and self-reported race and ethnicity were included. Multivariable linear regression evaluated the association between race and ethnicity groups and mean MBDA score, adjusting for potential confounders, including symptom duration and medication use. Sensitivity analyses substituted the Clinical Disease Activity Index (CDAI) and the Disease Activity Score-28 joints with erythrocyte sedimentation rate (DAS28-ESR) for the MBDA in multivariable models. We included 267 participants (86% female, mean age 52.7 ± 13.3 years). The majority were Latinx (n=137; 51%), followed by Asian (n=91; 34%). After adjustment, Latinx participants had the highest mean MBDA score (40.6± 2.1) compared with White participants at (32.8± 6.7). Black participants had the second highest mean MBDA score, followed by Asian participants (36.3± 5.3, 36.0± 2.7, respectively), although neither were significantly different from White participants. The trends observed for the CDAI and DAS28-ESR were similar to those for the MBDA. We found significantly higher disease activity measured by the MBDA and DAS28-ESR in Latinx participants compared with White participants. We also found significantly higher disease activity in Asian participants compared with White participants with the DAS28-ESR. Our findings, although limited by the small number of White participants in the referent group, suggest that RA disease activity measures may be influenced by external factors that have differential impacts by racial and ethnic group.

The Relationship Between FoxP3 and SOCs3 Gene Expressions and Disease Activity in Rheumatoid Arthritis.

Immune dysregulation plays an important role in the pathogenesis of rheumatoid arthritis (RA). The CD4+CD25 high FoxP3+ subset of regulatory T cells plays an essential role in preventing autoimmunity and maintaining immune homeostasis. Negative regulation of JAK/STAT signaling is controlled by Suppressor of Cytokine Signaling (SOCs3) proteins. SOCs is produced at lower levels in RA. Our aim was to evaluate the expressional dysregulation of SOCs3 and FoxP3 genes in RA patients in relation to disease activity. We have recruited 90 patients with RA and 60 healthy controls in case control study. Whole blood samples were collected from RA patients and healthy subjects. The measurement of FoxP3 and SOCs3 gene expression was performed by real-time PCR (qPCR). Patients with RA had significantly decreased expression levels of FoxP3 and SOCs3 genes in comparison with controls (P<0.001), in addition to the insignificance correlation of both genes with disease activity in RA patients. FoxP3 and SOCs3 genes showed significant defects in rheumatoid arthritis patients with no significant difference in disease activity.

The prevalence and correlation of depression and anxiety with disease activity in rheumatoid arthritis.

Depression and anxiety share similar symptoms with rheumatoid arthritis (RA) and these conditions are often not diagnosed or overlooked in RA. This study aimed to determine the prevalence of depression/anxiety in RA and their correlation with RA activity. Rheumatoid arthritis patients who presented at a rheumatology clinic were selected consecutively. The diagnosis of RA was confirmed by the ACR/EULAR criteria, disease activity was assessed by Disease Activity Score based on the 28-joint count (DAS28) and patients with DAS28 > 2.6 were considered to have active RA. The diagnosis of depression and anxiety was made by the Hospital Anxiety and Depression Scale (HADS). The Pearson test was used to determine the correlation between DAS28 and HADS scores. Two-hundred patients (female, 82%) with a mean age of 53.5 ±10.1 years and mean disease duration of 6.6 ±6.8 years were studied. Depression was diagnosed in 27 (13.5%) patients and anxiety in 38 (19%) patients. The DAS28 score correlated positively with depression (r = 0.173, p = 0.014) and anxiety score (r = 0.229, p = 0.001). In multiple logistic regression analysis after adjustment for all covariates, age < 40 years and female sex were independently associated with RA activity in patients with depression, with OR = 4.21 (p = 0.002) and OR = 3.56 (p = 0.028) respectively. These findings indicate that depression and anxiety are prevalent in RA and correlate positively with active disease in particular in depressive female patients aged < 40 years.

DAS28(3)CRP is a reliable measure of disease activity in pregnant women with rheumatoid arthritis.

The disease activity of rheumatoid arthritis (RA) in pregnancy is most commonly assessed with the modified Disease Activity Score (DAS)-28, the DAS28(3)CRP. However, the performance of the DAS28(3)CRP in pregnancy has not been compared to musculoskeletal ultrasound (MSK-US) as a gold standard. We performed a prospective pilot study to test the hypothesis that pregnancy-related factors limit the reliability of the DAS28(3)CRP. Pregnant women with RA were recruited from an Obstetric Rheumatology clinic and assessed during pregnancy (second (T2) and third (T3) trimesters) and postpartum with DAS28(3)CRP and MSK-US scores, with quantification of power Doppler (PD) signal in small joints (hands and feet). Age-matched non-pregnant women with RA underwent equivalent assessments. PD scores were calculated as mean scores of all joints scanned. We recruited 27 pregnant and 20 non-pregnant women with RA. DAS28(3)CRP was sensitive and specific for active RA in pregnancy and postpartum as defined by positive PD signal, but not in non-pregnancy. There were significant correlations between DAS28(3)CRP and PD scores throughout pregnancy (T2, r=0.82 (95% CI [0.42, 0.95], p<0.01); T3, r=0.68 (95% CI [0.38, 0.86], p<0.01)) and postpartum, r=0.84 (95% CI [0.60, 0.94], p<0.01), while this correlation in non-pregnancy was weaker (r=0.47 (95% CI [0, 0.77], p<0.05). This pilot study found that DAS28(3)CRP is a reliable measure of disease activity in pregnant women with RA. Based on these data, pregnancy does not appear to confound clinical evaluation of the tender and/or swollen joint counts.

Serum Level of Soluble Human Leukocyte Antigen G in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis.

This study aimed to evaluate the serum level of human leukocyte antigen G [HLA-G] in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) compared to healthy controls; moreover, it attempted to assess its relationship with SLE and RA disease activity indices. This descriptive study was conducted on 31 SLE patients (17 cases with a recent diagnosis and 14 cases with a previous diagnosis), 21 RA patients (7 cases with a recent diagnosis and 14 cases with a previous diagnosis), and 18 healthy controls who visited Ghaem Hospital affiliated to Mashhad University of Medical Sciences, Mahhad, Iran. SLE and RA activity indices were measured and recorded. Furthemore, soluble isoforms, including shed HLA-G1 and HLA-G5, were measured in serum samples via the ELISA method. A comparison of the five groups showed no significant differences in the serum level of sHLA-G. However, sHLA-G serum level was significantly higher in SLE and RA patients compared to healthy controls (P<0.05). sHLA-G level showed no correlation with disease duration and activity in SLE and RA patients (P>0.05). However, a strong positive correlation was observed between the serum level of sHLA-G and 24-h urine protein in the previously diagnosed SLE group (r=0.83, P=0.01). It seems that the serum level of sHLA-G is higher in RA and SLE patients compared to healthy controls. Furthermore, a strong correlation was found between sHLA-G serum levels and 24-h urine protein in cases with a previous diagnosis of SLE.