Rheumatoid Arthritis Subjects Research Articles

Protein Citrullination by Peptidyl Arginine Deiminase/Arginine Deiminase Homologs in Members of the Human Microbiota and Its Recognition by Anti-Citrullinated Protein Antibodies.

The human microbiome exists throughout the body, and it is essential for maintaining various physiological processes, including immunity, and dysbiotic events, which are associated with autoimmunity. Peptidylarginine deiminase (PAD) enzymes can citrullinate self-proteins related to rheumatoid arthritis (RA) that induce the production of anti-citrullinated protein antibodies (ACPAs) and lead to inflammation and joint damage. The present investigation was carried out to demonstrate the expression of homologs of PADs or arginine deiminases (ADs) and citrullinated proteins in members of the human microbiota. To achieve the objective, we used 17 microbial strains and specific polyclonal antibodies (pAbs) of the synthetic peptide derived from residues 100-200 of human PAD2 (anti-PAD2 pAb), and the recombinant fragment of amino acids 326 and 611 of human PAD4 (anti-PAD4 pAb), a human anti-citrulline pAb, and affinity ACPAs of an RA patient. Western blot (WB), enzyme-linked immunosorbent assay (ELISA), elution, and a test with Griess reagent were used. This is a cross-sectional case-control study on patients diagnosed with RA and control subjects. Inferential statistics were applied using the non-parametric Kruskal-Wallis test and Mann-Whitney U test generated in the SPSS program. Some members of phyla Firmicutes and Proteobacteria harbor homologs of PADs/ADs and citrullinated antigens that are reactive to the ACPAs of RA patients. Microbial citrullinome and homolog enzymes of PADs/ADs are extensive in the human microbiome and are involved in the production of ACPAs. Our findings suggest a molecular link between microorganisms of a dysbiotic microbiota and RA pathogenesis.

Abatacept increases T cell exhaustion in early RA individuals who carry HLA risk alleles.

Exhausted CD8 T cells (TEX) are associated with worse outcome in cancer yet better outcome in autoimmunity. Building on our past findings of increased TIGIT+KLRG1+ TEX with teplizumab therapy in type 1 diabetes (T1D), in the absence of treatment we found that the frequency of TIGIT+KLRG1+ TEX is stable within an individual but differs across individuals in both T1D and healthy control (HC) cohorts. This TIGIT+KLRG1+ CD8 TEX population shares an exhaustion-associated EOMES gene signature in HC, T1D, rheumatoid arthritis (RA), and cancer subjects, expresses multiple inhibitory receptors, and is hyporesponsive in vitro, together suggesting co-expression of TIGIT and KLRG1 may broadly define human peripheral exhausted cells. In HC and RA subjects, lower levels of EOMES transcriptional modules and frequency of TIGIT+KLRG1+ TEX were associated with RA HLA risk alleles (DR0401, 0404, 0405, 0408, 1001) even when considering disease status and cytomegalovirus (CMV) seropositivity. Moreover, the frequency of TIGIT+KLRG1+ TEX was significantly increased in RA HLA risk but not non-risk subjects treated with abatacept (CTLA4Ig). The DR4 association and selective modulation with abatacept suggests that therapeutic modulation of TEX may be more effective in DR4 subjects and TEX may be indirectly influenced by cellular interactions that are blocked by abatacept.

Association between Mediterranean‐dietary approaches to stop hypertension intervention for neurodegenerative delay diet and biomarkers of oxidative stress, metabolic factors, disease severity, and odds of disease in rheumatoid arthritis patients

AbstractThis research aimed to examine the association between the following Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) dietary pattern and oxidative stress indicators, metabolic factors, disease activity, and the odds of disease in patients with rheumatoid arthritis (RA). In this cross‐sectional study, we included 101 patients with RA and 101 healthy individuals. The MIND diet score was measured using a semi‐quantitative Food Frequency Questionnaire (FFQ) with 147 food items. Total capacity antioxidant (TCA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and malondialdehyde (MDA) serum concentrations were evaluated by ELISA, and the disease severity was measured regarding the disease activity score 28 (DAS‐28) criteria. The average score of the MIND diet was substantially lower in the RA subjects than in the healthy people (p < .001). Individuals with a higher MIND diet score had lower odds of RA than those with a low score (p < .001). There was no remarkable link between the MIND diet and oxidative stress factors (p > .05). A reverse association was found between the MIND diet score and disease activity (p < .05). The MIND diet was significantly and negatively correlated with triglycerides, low‐density lipoprotein cholesterol, total cholesterol, fasting blood glucose, and hemoglobin A1C. There was a positive association between the diet and high‐density lipoprotein cholesterol. The findings indicate that following the MIND diet may decrease disease activity and the odds of RA. Also, high adherence to the MIND diet may improve the lipid profile and blood glucose status in RA patients.

Macrophage extracellular traps require peptidylarginine deiminase 2 and 4 and are a source of citrullinated antigens bound by rheumatoid arthritis autoantibodies.

Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis, but the sources of citrullinated antigens as well as which peptidylarginine deiminases (PADs) are required for their production remain incompletely defined. Here, we investigated if macrophage extracellular traps (METs) could be a source of citrullinated proteins bound by APCAs, and if their formation requires PAD2 or PAD4. Thioglycolate-induced peritoneal macrophages from wild-type, PAD2-/-, and PAD4-/- mice or human peripheral blood-derived M1 macrophages were activated with a variety of stimulants, then fixed and stained with DAPI and either anti-citrullinated histone H4 (citH4) antibody or sera from ACPA+ or ACPA- rheumatoid arthritis subjects. METs were visualized by immunofluorescence, confirmed to be extracellular using DNase, and quantified. We found that ionomycin and monosodium urate crystals reliably induced murine citH4+ METs, which were reduced in the absence of PAD2 and lost in the absence of PAD4. Also, IgG from ACPA+, but not ACPA-, rheumatoid arthritis sera bound to murine METs, and in the absence of PAD2 or PAD4, ACPA-bound METs were lost. Finally, ionomycin induced human METs that are citH4+ and ACPA-bound. Thus, METs may contribute to the pool of citrullinated antigens bound by ACPAs in a PAD2- and PAD4-dependent manner, providing new insights into the targets of immune tolerance loss in rheumatoid arthritis.

Identification of circulating autoantibodies to non-modified proteins associated with ACPA status in early rheumatoid arthritis.

To discover autoantibodies to non-modified proteins associated with the presence/absence of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). The autoantibody repertoire of 80 ACPA negative and 80 ACPA positive RA subjects from the Swedish population-based Epidemiological Investigation of RA (EIRA) cohort was screened using a suspension bead array built on protein fragments earlier described as autoimmunity targets. Four autoantibodies positive in the initial screening were validated in another set of EIRA samples containing 317 ACPA-positive, 302 ACPA-negative and 372 age- and sex-matched controls. The relationship between the four autoantibodies and lung abnormalities on high-resolution computed tomography (HRTC) was examined in 93 early RA patients from LURA cohort. Association between the autoantibodies, smoking and MHC class II alleles was assessed by logistic regression analysis. : Anti-ANOS1 and anti-MURC IgG levels were associated with ACPA-positive status (OR = 3.02; 95% CI 1.87-4.89; and OR = 1.86; 95% CI 1.16-2.97, respectively) and increased in ACPA-positive patients compared with controls. Anti-ANOS1 IgG was associated with smoking habit (OR = 2.11; 95% CI 1.22-3.69) and anti-MURC IgG with the presence of the MHC class II "shared-epitope" genes (OR = 1.95; 95% CI 1.11-3.46). Anti-TSPYL4 IgG was associated with ACPA-negative (OR = 0.41; 95% CI 0.19-0.89). Anti-TSPYL4 IgG and anti-MAP2K6 IgG levels were increased in the ACPA-negative patients compared with controls. Presence of anti-MAP2K6 IgG and anti-TSPYL4 IgG correlated negatively with HRCT-defined lung abnormalities. These four autoantibodies may be useful in diagnostics and in predicting clinical phenotypes of RA.

Comparison of Carotid Ultrasound Parameters in Patients with Rheumatoid Arthritis and Control Subjects: A Cross-sectional Study

Introduction: Rheumatoid Arthritis (RA) is considered one of the risk factors for Cardiovascular Disease (CVD). Carotid ultrasound is used to assess the extent of subclinical atherosclerosis in patients with RA. Very few studies have evaluated all carotid ultrasound findings, such as Carotid Intima-media Thickness (CIMT), carotid diameters like Luminal Diameter (LD) and Interadventitial Diameter (IAD), and plaque characteristics in patients with RA. Aim: To assess and compare the various carotid parameters in RA patients with controls and also to evaluate their association with age and duration of onset of the disease. Materials and Methods: A single-centre cross-sectional study was conducted at the Department of Radiology, GCS Medical College and Hospital, Ahmedabad, Gujarat, India, involving 40 patients with RA (Group-RA) and 40 controls (Group-C). Patients were further divided into three age subgroups. Carotid ultrasound parameters like CIMT, LD, IAD, and plaque were evaluated in both groups. Continuous variables were analysed using the t-test, and categorical data were analysed using the Chi-squared test. A p-value of < 0.05 was considered statistically significant. Results: Age- and sex-matched controls were included with 28 females and 12 males in both the study groups. The mean LD and IAD were significantly higher in the RA group than in controls (Mean LD- 5.88±0.97 mm vs 5.26±1.08 mm with p=0.009; Mean IAD- 6.85±0.89 mm vs 6.30±0.87 mm with p=0.006). The mean CIMT was higher in the RA group but not statistically significant (0.57±0.13 mm vs 0.54±0.12 mm with p=0.256). Further subgroup analysis showed that all carotid parameters were statistically significant in the 31-60 years age group as compared to 18-30 years and 61-80 years subgroups. The effect of the duration of the disease (>5 years) on the carotid parameters was also significantly higher in the 30-60 age group (p<0.001). Conclusion: The present study showed that various carotid ultrasound parameters can be used as a screening tool in the follow-up of RA patients to detect early changes in atherosclerosis, with LD and IAD having superior predictive capability. The study further showed that carotid ultrasound parameters have a better predictive value in the 31-60 years age group.

Comparison of the intima-media thickness of the common carotid artery in patients with rheumatoid arthritis: A single-center cross-sectional case-control study, and a brief review of the literature.

Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease affecting 0.5%-1%of adults worldwide. The carotid intima-media thickness (CIMT) is a simple, reliable, noninvasive marker for subclinical atherosclerosis. The aim of this study was to compare the intima-media thickness of the common carotid artery in patients with RAwith that of healthy patients. In this case-control study, subjects were recruited from the patients who presented to a private rheumatology clinic. RAwas documented by a rheumatologist. All subjects underwent an ultrasound examination of the carotid artery to assess CIMT. Subjects with RA filled out the disease activity score (DAS28) questionnaire. Sixty-two subjects (31 subjects with RA and 31 healthy subjects) took part in the study. The mean age of the subjects in the RA and the control groups was 42.39 ± 12.98 and 44.48 ± 13.56 years, respectively. Values of CIMT were significantly greater in RA subjects compared with their healthy counterparts (p < 0.001). The CIMTincreased significantly with increased disease severity (r = 0.73). Subjects were divided into two age groups (≤40and >40 years). A comparison of CIMT in the mentioned subgroups revealed a remarkable difference in CIMT values between those of the RA patients and those of their control counterparts in both age groups(p = 0.002 and p < 0.001 for those below and above 40 years, respectively). CIMT could be used as an efficient clinical index for identifying the early stages of atherosclerosis and predicting cardiovascular events following atherosclerosis in RA patients.

Evaluating the potential of matrix metalloproteinase as a diagnostic biomarker in rheumatoid arthritis and periodontitis: A systematic review and meta-analysis.

Matrix metalloproteinases (MMPs) play a crucial role in the pathogenesis of several chronic diseases including rheumatoid arthritis (RA) and periodontitis (PD). RA patients with periodontitis (RA-PD) are associated with elevated inflammatory burden due to increased production of proinflammatory cytokines. Controlling upregulated MMPs activity in these patients may have potential therapeutic effects. Therefore, aim of this study is to address the focused question: "Do RA subjects with concurrent PD have different levels of MMPs in comparison to RA alone, PD alone and HC subjects?" The systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search from 4 electronic databases (EMBASE, Medline, Web of Science, and Cochrane library) and manual search was performed from inception to July 2023. Quality assessment of each article was done using Newcastle-Ottawa Scale. Meta-analyses derived results were summarized as standardized mean difference (SMD) with 95% confidence intervals. A total of 879 articles were extracted. Following screening and full text assessment, 9 studies were included. MMP-1, MMP-3, MMP-8, MMP-9, and MMP-13 were consistently elevated in RA-PD subjects. MMP-8 levels were found to be higher in RA-PD subjects compared with RA alone, PD alone, and HC in 3 studies reporting GCF levels (SMD = 1.2; Z = 2.07; P = .04) and 2 studies reporting serum levels (SMD = 0.87; Z = 4.53; P < .00001). RA-PD group showed significantly higher MMP levels in their serum and GCF compared with HC, RA, and PD alone individuals. MMP-8 may serve as a reliable biomarker in the diagnosis and management of RA-PD subjects.

Associations of inflammatory polyarthritis with clinical and radiological findings of temporomandibular disorders

Objective To evaluate the association of different forms of inflammatory polyarthritis with clinical signs of temporomandibular disorders (TMD) and radiological findings in temporomandibular joint (TMJ), based on a nationwide health survey in Finland. The aim was also to assess the presence of clinical and radiological TMD findings in subjects with increased risk for developing rheumatoid arthritis (RA). Material and methods A nationally representative sample included 6331 Finnish adults who participated in the Health 2000 Survey (BRIF8901). Subjects were examined for signs of TMD, findings in panoramic radiograph of TMJ, musculoskeletal health and serology (rheumatoid factor, RF, and anti-cyclic citrullinated peptide, aCCP). Results Sixty-four percent of seronegative RA and 60% of seropositive RA subjects had at least one sign of TMD. While adjusting for confounding factors (gender, age, dentures and smoking history), RA was significantly associated with crepitation and abnormal radiological findings in TMJ. Seronegative RA was also associated with restricted mouth opening. Systemic autoimmunity associated with RA (“at risk of RA”) was not associated with clinical or radiological TMD findings. Conclusions Clinical and radiological findings of TMD are more prevalent among subjects with inflammatory polyarthritis than among the population in general in the Finnish adult population.

Elevated triglyceride levels are associated with increased risk for major adverse cardiovascular events in statin-naïve rheumatoid arthritis patients: A nationwide cohort study

ObjectivesTo investigate the association between the four components of the lipid profile (total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)) at baseline and composite major adverse cardiovascular events (MACEs) in statin-naïve rheumatoid arthritis (RA) patients with no previous history of cardiovascular events. MethodsThis nationwide population-based cohort study was performed on a total of 15,216 statin-naïve RA patients. The end point was a composite of clinical events, including myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death. We compared the incidence of and risk for clinical events according to each lipid variable. ResultsDuring follow-up (median 4.70 years), the incidence of MACE per 1000 person-years was 7.27. Among the four lipid components, only higher baseline TG levels were significantly associated with increased risk for composite MACE in RA subjects. The risk for composite MACE was significantly higher in the third (adjusted hazard ratio (HR), 1.35 [95% confidence interval (CI), 1.03–1.78]) and highest quartiles (adjusted HR, 1.74 [95%CI, 1.33–2.28]) of baseline TG level versus the lowest quartile. ConclusionsIn statin-naïve RA patients, increased TG level is associated with increased risk for MACE. Therefore, screening and intervention for increased TG level may be clinically beneficial in this population.

Integrating Chinese Herbal Medicine into Conventional Care Was Related to Lower Risk of Sarcopenia Among Rheumatid Arthritis Patients: A Retrospective, Population-Based Study.

Sarcopenia is a frequently observed comorbidity of rheumatoid arthritis (RA) due to the chronic activation of the innate immune system. Accumulating evidence has indicated that Chinese herbal medicine (CHM) safely suppresses proinflammatory pathways and controls inflammation-associated disease, but its effect in reducing the risk of developing sarcopenia among RA subjects has not been established. We conducted a population-level cohort study to compare the sarcopenia risk in patients with RA who use or do not use CHM. Using claims from a nationwide insurance database, we recruited patients with newly diagnosed RA and without sarcopenia between 2002 and 2010. Propensity score matching was applied to randomly select sets of CHM users and non-CHM users to compare the sarcopenia risk until the end of 2013. The risk of new-onset sarcopenia was assessed using the Cox proportional hazards model. As compared to non-CHM users, those receiving CHM treatment had a lower incidence of sarcopenia (7.69 vs 9.83 per 1000 person-years). CHM was correlated with a decreased chance of sarcopenia after controlling for potential covariates. Notably, use of CHM for more than two years may diminish the risk of getting sarcopenia by about 47% when taken as prescribed. Prescriptions of several herbal formulae may benefit the reduction of sarcopenia risk, such as Yan-Hu-Suo, Bei-Mu, Da-Huang, Huang Qin, Ping-Wei-San (PWS), Shu-Jing-Huo-Xue-Tang (SJHXT) and Chuan-Xiong-Cha-Tiao-San (CXCTS). This study produced new evidence as it is the first to show that the longer duration of CHM use was correlated to reduced risk of sarcopenia in a dose-dependent manner, implying that CHM treatment could be embraced as a routine care strategy for preventing sarcopenia.

Epigenome-wide methylation haplotype association analysis identified HLA-DRB1, HLA-DRB5 and HLA-DQB1 as risk factors for rheumatoid arthritis.

The aim of this study was to compare nonrandom associations between physically adjacent single methylation polymorphism loci among rheumatoid arthritis (RA) and normal subjects for investigating RA-risk methylation haplotypes (meplotype). With 354 ACPA-positive RA patients and 335 normal controls selected from a case-control study based on Swedish population, we conducted the first RA epigenome-wide meplotype association study using our software EWAS2.0, mainly including (i) converted the β value to methylation genotype (menotype) data, (ii) identified methylation disequilibrium (MD) block, (iii) calculated frequent of each meplotypes in MD block and performed case-control association test and (iv) screened for RA-risk meplotypes by odd ratio (OR) and p-values. Ultimately, 545 meplotypes on 334 MD blocks were identified significantly associated with RA (p-value<.05). These meplotypes were mapped to 329 candidate genes related to RA. Subsequently, combined with gene optimization, eight RA-risk meplotypes were identified on three risk genes: HLA-DRB1, HLA-DRB5 and HLA-DQB1. Our results reported the relationship between DNA methylation pattern on HLA-DQB1 and the risk of RA for the first time, demonstrating the co-demethylation of 'cg22984282' and 'cg13423887' on HLA-DQB1 gene (meplotype UU, p-value=2.90E-6, OR=1.68, 95% CI=[1.35, 2.10]) may increase the risk of RA. Our results demonstrates the potential of methylation haplotype analysis to identify RA-related genes from a new perspective and its applicability to the study of other disease.

Role of some inflammasomes in rheumatoid arthritis patients in Egypt

AimThis study aims to demonstrate the role of some inflammasomes genes: NLRC4 (the NLR family, CARD domain-containing protein 4), NLRP1 (NLR family, pyrin domain-containing 1), ASC (Apoptosis-associated speck-like protein containing a CARD), and CASPASE-1 in the pathogenesis of Rheumatoid arthritis (RA) in Egyptian population.Main methodsThe expression level of NLRC4, NLRP1, ASC, and CASPASE-1 within PBMCs isolated from all RA subjects by quantitative real-time PCR. GAPDH gene was used as a reference gene. Measurement of serum level of IL-1β and IL-18 was performed using ELISA.Key findingsResults showed dysregulated inflammasomes expression that may participate in the pathogenesis of the inflammatory process of the disease.SignificanceUnderstanding the role of inflammasomes in RA pathogenesis helps in finding promising therapy for the treatment and management of this disease.

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study.

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan-Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8-91.5%) at month 12, 78.8% (95% CI: 78.8-85.2%) at month 24, 63.8% (95% CI: 55.1-73.8%) at month 36, and 59.9% (95% CI: 55.1-73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results.

Magnetic resonance imaging RAMRIS-SAFE score-A low-risk effective measure of rapid response to therapy in rheumatoid arthritis clinical trials.

To assess the rapidity of magnetic resonance imaging (MRI) measured synovitis (as measured by synovial thickening using the RAMRIS-SAFE score) and bone edema in active rheumatoid arthritis (RA) subjects treated with golimumab. Secondary aims: to correlate MRI measures with disabilities of the arm, shoulder, and hand (DASH), physician global (PhysG) and patient global (PatG) assessments. Patients with active RA and inadequate response to methotrexate were recruited. Active RA was defined as RA with a Disease Activity Score of 28 joints - C-reactive protein ≥4.2 at screening AND active disease (synovitis and edema) of the chosen hand or wrist on MRI at screening, as determined by the central blinded MRI reader (PB). Outcomes measures were assessed at baseline, 2, 6, and 12 weeks. MRI results were interpreted by one experienced observer (PB), blinded to clinical measures. Pearson's correlation co-efficient (SPSS) was used to express the relationship between DASH, PhysG, PatG and MRI measures. Eighteen patients were included in the study. All subjects completed follow-up visits and MRI assessment. Mean age was 60.6 years (range 22-72), and 10 were female, 8 male, and disease duration was mean 4.72 years (range 1-28); all patients were taking background methotrexate. The changes in MRI synovial volume were evident by visit 2. The strongest correlations with the DASH for MRI parameters were total synovial thickening (0.923) and edema (0.921). Golimumab was associated with rapid improvement in clinical measures and patient-reported outcome measures. Mean synovial thickening demonstrated early rapid improvement. MRI synovial thickening demonstrated a strong correlation with DASH, PatG and PhysG.

Determination of serum and gingival crevicular fluid levels of omentin in healthy and rheumatoid arthritis subjects with and without periodontitis.

The aim of this study was to assess and correlate the serum and GCF levels of omentin with the periodontal status of rheumatoid arthritis (RA) patients with and without periodontitis. Forty-four patients were divided into four groups: group H: 11 systemically and periodontally healthy subjects; group P: 11 systemically healthy subjects with periodontitis; group RA: 11 periodontally healthy subjects with rheumatoid arthritis and group RA + P: 11 rheumatoid arthritis subjects with periodontitis. Periodontal parameters (plaque index, modified gingival index, probing depth, and clinical attachment level) were recorded and serum and GCF samples were collected for the estimation of omentin using ELISA. The mean value of plaque index, modified gingival index, probing depth, and clinical attachment level were significantly higher whereas serum and GCF omentin levels were found to be decreased in group IV when compared to the other groups. The significant correlation was found between the serum and GCF omentin levels with all the periodontal parameters. The omentin level in serum and GCF was found to be lower in RA patients with periodontitis. It is also inversely correlated with the periodontal parameters. Thus, omentin can serve as a significant diagnostic and therapeutic tool in both periodontal and rheumatoid disease.

Effect of treatment regimen of the rheumatoid arthritis patients on the risk of coronavirus disease 2019 by modulating the inflammatory mediators.

The therapeutic profile of the patients with rheumatoid arthritis (RA) commonly consists of immunosuppressive and anti-inflammatory compounds. Here in this research, we assessed the potential effect of drug treatment in the RA patients in increasing the risk of coronavirus disease 2019 (COVID-19) infection. In this retrospective cross-sectional study, 200 subjects with RA were recruited. The treatment profile of the subjects for the past 6months was collected. The COVID-19 diagnosis was implemented based on the standard molecular tests and clinical examinations. Serum concentration of cytokines was measured using enzyme-linked immunosorbent assay (ELISA). It was detected that there was an increased risk of COVID-19 in RA subjects receiving Etanercept (OR = 3.51, 95% CI 1.19-10.30, P = 0.022). Concentrations of Interleukin (IL)-1β, Interferon (IFN)-γ, Tumor necrosis factor (TNF)-α, IL-6, IL-17A, and IL-23 were significantly higher in the RA patients with COVID-19 relative to RA cases without COVID-19. In RA/COVID-19 cases receiving Etanercept, serum levels of TNF-α, IL-1β, and IL-6 were significantly lower than RA/COVID-19 subjects without Etanercept therapy. It seems that Etanercept therapy in RA cases might increase proneness of the COVID-19 risk in these cases. The mechanism of this increased risk may stem from suppressing a protective immunity state in the RA cases.

Life satisfaction, generalized sense of self-efficacy and acceptance of illness in rheumatoid arthritis patients depending on age and severity of the disease.

Rheumatoid arthritis (RA) is a chronic autoimmune condition characterized by periods of exacerbation (physical limitations, depressed mood, depressive states and decreased life satisfaction) and remission (hope of health improvement). Our objective was to present social functioning of RA patients taking into consideration their age and employing selected determinants: satisfaction with life, generalized sense of self-efficacy and acceptance of illness. Standardized tools were employed: the Satisfaction with Life Scale, Generalized Self Efficacy Scale and Acceptance of Illness Scale. The study group included 46 RA patients aged 18-45 years and 54 RA patients aged over 60 years. The control group consisted of 24 non-RA subjects in every group. Rheumatoid arthritis patients in the period of disease exacerbation reported low and moderate levels of satisfaction with life, in the patients in remission period the score was moderate, while the control group subjects described their level of satisfaction with life as high and moderate. The level of acceptance of illness was described by the RA patients in the period of disease exacerbation as 20.4/40 points; the patients in remission defined their level of acceptance of illness as 29.38/40 points. The patients with RA exacerbation showed a low sense of self-efficacy, yet a large group of such patients also presented high self-efficacy levels and the majority of the RA subjects in remission reported a high sense of self-efficacy. In the RA patients, satisfaction with life, generalized sense of self-efficacy and acceptance of illness were closely related and affected their general psychosocial functioning.

Serum Protein Profiles of Rheumatoid Arthritis Samples –A Case Study

Rheumatoid arthritis is the 3rd autoimmune disease with a degenerative, chronic inflammatory characteristics. Diagnosis criteria suggested by American College of Rheumatology/European League Against Rheumatism based on serological blood tests and acute phase reactant measurements analyses are the key steps in the diagnosis of disease. Genetic, environmental, or hormonal factors may have contributed to the development of this illness. Characterization of Rheumatoid arthritis-related proteins can be beneficial for early diagnosis, prognosis, and therapeutic aspects. During the current study the serum samples of rheumatoid arthritis subjects were analyzed using serum electrophoresis and Orbitrap Liquid Chromatography-Mass Spectrometry along with biochemical confirmatory tests. The patterns of total protein and gamma globulin ratios, interrelationships of the different test criteria for diagnosis indicated unique pattern. The orbitrap Liquid Chromatography-Mass Spectrometry analyses indicated the presence of 20 unique proteins exclusively in the subjects with Rheumatoid arthritis. Testicular protein Li 227, uncharacterized protein Q6DHW4 and protein S 100-A7 can aid in the early confirmation of the disease. Further analyses of these specific proteins may help in the prognosis, diagnosis, and therapeutic aspect of the disease.

Peripheral blood cellular dynamics of rheumatoid arthritis treatment informs about efficacy of response to disease modifying drugs

Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation and is mediated by multiple immune cell types. In this work, we aimed to determine the relevance of changes in cell proportions in peripheral blood mononuclear cells (PBMCs) during the development of disease and following treatment. Samples from healthy blood donors, newly diagnosed RA patients, and established RA patients that had an inadequate response to MTX and were about to start tumor necrosis factor inhibitors (TNFi) treatment were collected before and after 3 months of treatment. We used in parallel a computational deconvolution approach based on RNA expression and flow cytometry to determine the relative cell-type frequencies. Cell-type frequencies from deconvolution of gene expression indicate that monocytes (both classical and non-classical) and CD4+ cells (Th1 and Th2) were increased in RA patients compared to controls, while NK cells and B cells (naïve and mature) were significantly decreased in RA patients. Treatment with MTX caused a decrease in B cells (memory and plasma cell), and a decrease in CD4 Th cells (Th1 and Th17), while treatment with TNFi resulted in a significant increase in the population of B cells. Characterization of the RNA expression patterns found that most of the differentially expressed genes in RA subjects after treatment can be explained by changes in cell frequencies (98% and 74% respectively for MTX and TNFi).