Clinical Parameters Of Rheumatoid Arthritis Research Articles

Fibromyalgia and mental health in rheumatoid arthritis: a cross-sectional prevalence study from the COVID-19 pandemic

ObjectivesThis study evaluated the prevalence of fibromyalgia (FM), anxiety and depression in patients with rheumatoid arthritis (RA) and their effects on the clinical parameters of RA during the COVID-19 pandemic.DesignCross-sectional,...

The Role of Different Circulating T Follicular Helper Cell Markers in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic incurable inflammatory autoimmune disease. T follicular helper (Tfh) cells expressing different markers play critical roles in the development of RA. However, their specific mechanisms of action and association with RA clinical parameters are not clear. We therefore performed a cohort study to investigate the effects of different Tfh cell markers on RA pathogenesis. We retrospectively reviewed clinical data from 30 patients diagnosed with RA and 30 healthy controls (HCs) who visited our hospital. Based on X-ray findings, the patients were divided into a joint bone erosion group (n = 17) and a non-erosive joint bone group (n = 13). Using flow cytometry, we determined the frequencies of five peripheral blood CD4+ Tfh cell types characterized by different markers, and examined these cell types for correlations with clinical parameters. RA patients exhibited higher frequencies of CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+OX40+, and CD4+CXCR5+CD40L+ Tfh cells than HCs. CD4+CXCR5+, CD4+CXCR5+CD40L+, and CD4+CXCR5+OX40+ Tfh cell frequencies positively correlated with disease activity score-28 with erythrocyte sedimentation rate (DAS28-ESR), while those of CD4+CXCR5+ and CD4+CXCR5+CD40L+ Tfh cells were related to rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies. In RA patients without joint bone erosion, CD4+CXCR5+CD40L+ Tfh cell frequencies were positively correlated with both RF and DAS28-ESR. Serum anti-CCP antibody levels and CD4+CXCR5+ICOS+ Tfh cell frequencies were also positively correlated. Circulating CD4+CXCR5+CD40L+ Tfh cells appear to play critical roles in RA pathogenesis, and restricting CD4+CXCR5+CD40L+ Tfh cells may be a therapeutic strategy for controlling RA.

Disease activity and subcutaneous nodules are associated to severe periodontitis in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) was significantly associated with increased overall risk of periodontitis, both chronic, inflammatory pathologies leading to connective tissue breakdown and bone destruction. To identify clinical and/or serological variables routinely evaluated during follow-up of people with RA which are associated with the severity of their periodontal disease. An observational, cross-sectional study was carried out, which included RA patients according to ACR/EULAR 2010 criteria having chronic periodontal disease. RA clinical parameters (disease duration, erythrocyte sedimentation rate, serum C-reactive protein, disease activity (DAS28) and rheumatoid factor, presence of bone erosions and rheumatic nodules) and also corticosteroid therapy were considered. Periodontitis was evaluated according to the American Academy of Periodontology (1999) and chronic periodontitis was assessed by full mouth periapical radiographic examination, periodontal probing depth, clinical attachment level and bleeding index. A total of 110 subjects with RA and chronic periodontitis were included. The female/male relation was 5.1, and no significant differences between genres were found in rheumatic or oral variables. RA patients with longer disease duration, higher disease activity and with rheumatic nodules had significantly greater periodontitis severity. Multivariate analysis confirmed that severe periodontitis was associated with DAS283 4.1 (OR 51.4, CI 95% 9.4-281.5) and the presence of rheumatic nodules (OR 6.4, CI 95% 1.3-31.6). Disease activity and rheumatic nodules were strongly associated with severe periodontitis. Based on these findings it would be desirable to include interdisciplinary management at an early stage of RA to ensure comprehensive treatment of both pathologies.

Activated Platelets Convert CD14+CD16- Into CD14+CD16+ Monocytes With Enhanced FcγR-Mediated Phagocytosis and Skewed M2 Polarization.

Monocytes are important cellular effectors of innate immune defense. Human monocytes are heterogeneous and can be classified into three distinct subsets based on CD14 and CD16 expression. The expansion of intermediate CD14+CD16+ monocytes has been reported in chronic inflammatory diseases including rheumatoid arthritis (RA). However, the mechanism underlying induction of CD16 and its role in monocytes remains poorly understood. Here, we demonstrate that activated platelets are important for induction of CD16 on classical CD14+CD16- monocytes by soluble factors such as cytokines. Cytokine neutralization and signaling inhibition assays reveal that sequential involvement of platelet-derived TGF-β and monocyte-derived IL-6 contribute to CD16 induction on CD14+CD16- monocytes. Activated platelet-induced CD16 on monocytes participates in antibody-dependent cellular phagocytosis (ADCP) and its level is positively correlated with phagocytic activity. CD14+CD16- monocytes treated with activated platelets preferentially differentiate into M2 macrophages, likely the M2c subset expressing CD163 and MerTK. Lastly, the amount of sCD62P, a marker of activated platelets, is significantly elevated in plasma of RA patients and positively correlates with clinical parameters of RA. Our findings suggest an important role of activated platelets in modulating phenotypical and functional features of human monocytes. This knowledge increases understanding of the immunological role of CD14+CD16+ cells in chronic inflammatory diseases.

Increase in MEG3, MALAT1, NEAT1 Significantly Predicts the Clinical Parameters in Patients With Rheumatoid Arthritis

Aim: This study investigated deregulation of lncRNAs MEG3, MALAT1, NEAT1 and their associations with clinical parameters in rheumatoid arthritis (RA). Materials & methods: LncRNAs MALAT1, MEG3, NEAT1 were quantified from peripheral blood mono-nuclear cells (PBMCs) and plasma of 82 RA patients with 15 matched controls and from knee fluid of 24 RA patients with ten osteoarthritis controls. Multivariate analyses were performed among lncRNAs and clinical parameters of RA. Results: MALAT1, MEG3, NEAT1 were increased in PBMCs, plasma, synovial fluid(p<0.05) of RA patients. Significant correlations were observed for MEG3 with TJC (r=0.29), NEAT1 with TJC (r=0.49), swollen joint count (r=0.20), DAS28-CRP (r=0.29). Multivariate analysis revealed that 48.5% of TJC and 31.5% of swollen joint count could be predicted by lncRNAs. Conclusion: The findings suggested that the lncRNAs might be explored as probable markers in monitoring disease activity.

Expression patterns of CD28 and CTLA-4 in early, chronic, and untreated rheumatoid arthritis.

BackgroundT‐cell activation pathways have been proposed as trigger mechanisms in the pathogenesis of rheumatoid arthritis (RA). CD28 and CTLA‐4 play major roles in regulating the stimulatory and inhibitory co‐signals in T cells.ObjectiveTo analyze the association between soluble and surface expression of CD28 and CTLA‐4 with the clinical parameters of RA patients.MethodsA total of 35 RA patients classified as early RA (n = 14), chronic RA (n = 14), and untreated RA (n = 7), as well as 7 age‐ and sex‐matched control subjects (CS) were included. Surface expression of CD28 and CTLA‐4 on T cells was evaluated by flow cytometry. Soluble levels of CD28 (sCD28), CTLA‐4 (sCTLA‐4), and anti‐CCP antibodies were measured by ELISA.ResultsA significant lower percentage of CD8 + T cells positive to CD28 (CS = 64.9% vs RA = 42.7%, P = .04), and diminished surface expression of CD28 (CS: MFI = 122.9 vs RA: MFI = 33.1, P = .006), were found in chronic RA patients compared to CS. Higher sCD28 were observed in early RA patients compared with chronic RA patients (P < .05). sCTLA‐4 was found increased in untreated RA patients compared to early RA patients (P < .05). sCD28 concentration correlated with anti‐CCP levels (rho = −0.12; P = .032). The soluble and surface expressions of CTLA‐4 were not associated with RA clinical parameters.ConclusionsIn RA, the percentage of CD8 + CD28+ T cells decreases and expresses fewer membrane CD28 than CS. sCD28 levels are lower in chronic RA and are associated negatively with anti‐CCP levels. sCTLA 4 levels are lower in early RA patients than in untreated 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.

CCR6+ group 3 innate lymphoid cells accumulate in inflamed joints in rheumatoid arthritis and produce Th17 cytokines

BackgroundRecent studies show that innate lymphoid cells (ILCs) contribute to the development of chronic inflammation and autoimmune disease. In this study, we assessed the ILC function in the development of rheumatoid arthritis (RA).MethodsIn a mouse model of collagen-induced arthritis (CIA), we identified and purified the ILC subsets in peripheral blood (PB), local lymph nodes (LNs), and joints by fluorescence-activated cell sorting and used quantitative PCR to assess the expression levels of representative cytokines. We also correlated the frequencies of each ILC subset in synovial fluid (SF) with clinical parameters in RA patients.ResultsIn the CIA model, the proportion of CCR6+ ILC3s to total ILCs in joints with active inflammation significantly increased relative to non-arthritic joints (median 29.6% vs 16.7%, p = 0.035). CCR6+ ILC3s from mice with arthritis expressed significantly higher levels of IL-17A and IL-22 mRNA than did comparable cells from control mice (p < 0.0001 and p = 0.015). In RA patients, the proportion of CCR6+ ILCs in SF was positively correlated with tender joint counts (TJC) and swollen joint counts (SJC) (ρ=0.689, p = 0.0032 and ρ=0.644, p = 0.0071, respectively). Levels of CC chemokine ligand 20 (CCL20) increased in SF of patients with RA and were significantly correlated with CCR6+ ILC number (ρ=0.697, p = 0.0001).ConclusionCCR6+ ILC3s may play some roles in the development of RA through the production of IL-17 and IL-22.

Effects of coenzyme Q10 supplementation on matrix metalloproteinases and DAS-28 in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled clinical trial.

This study aimed to assess the effect of CoQ10 supplementation on serum matrix metalloproteinases (MMPs) and clinical parameters in rheumatoid arthritis (RA) patients. In this randomized, double-blind, placebo-controlled trial, 54 RA patients who fulfilled the eligibility criteria (18-56years, diagnosed at least 6months ago, with DAS-28 > 3.2) were randomly assigned into two groups to receive 100mg/day CoQ10 (n = 27) or placebo (n = 27) for 2months. Serum MMP-1 and MMP-3 levels and clinical status using disease activity score in 28 joints (DAS-28) were assessed before and after supplementation. Data were analyzed using χ2, independent sample t test, paired t test, Wilcoxon, Mann-Whitney, and analysis of covariance. A significant reduction was observed in both CoQ10 and placebo groups in the medians of serum MMP-1 (0.2 to 0.16, P < 0.001), (0.18 to 0.15, P = 0.001); swollen joint count (2 to 0, P < 0.001), (2 to 0, P = 0.009); and the means of DAS-28 (5.01 ± 1.21 to 2.34 ± 0.68, P < 0.001), (4.88 ± 0.96 to 4.04 ± 1.36, P = 0.009) respectively. Serum MMP-3 level increased significantly in placebo group (2.26 to 2.57, P = 0.020), and the MMP-3 changes between groups were significant (P = 0.027). Furthermore, significant reductions were only observed in ESR, pain score, and tender joint count in CoQ10 group compared with baseline (P = 0.001, P < 0.001, and P < 0.001, respectively). Significant differences were observed between two groups in DAS-28, pain score, and swollen and tender joint count after the intervention (P < 0.001, P < 0.001, and P = 0.012 and P < 0.001, respectively). It seems that CoQ10 may provide a new complementary approach for RA patients.Key Points• CoQ10 supplementation in RA patients attenuated serum MMP-3 level.• CoQ10 supplementation in RA patients improved clinical outcomes and ameliorated disease severity.• CoQ10 may provide a new complementary approach for patients with RA.

Decreased Gene Expression of Epstein–Barr Virus-Induced Gene 3 (EBI-3) may Contribute to the Pathogenesis of Rheumatoid Arthritis

ABSTRACTBackground: Interleukin-35 (IL-35) is a member of the IL-12 family of heterodimeric cytokines produced by regulatory T (Treg) cells. This immunosuppressive cytokine can prevent exaggerated inflammatory responses like those responsible for the development of rheumatoid arthritis (RA). This study aims to determine the correlation between the gene expression of Epstein–Barr virus-induced gene 3 (EBI-3) and IL-12A (p35) subunits of IL-35 in peripheral blood leukocytes with immunological and clinical parameters in RA patients.Methods: We recruited 47 patients with RA and 44 healthy subjects. The disease activity score-28 (DAS-28) was assessed by an expert rheumatologist and the plasma levels of neopterin and anti-cyclic citrullinated peptide (anti-CCP) was measured using ELISA method also Serum rheumatoid factor (RF) was assessed by the agglutination test. For the evaluation of IL-12A and EBI-3 gene expression, we used qPCR.Results: We did not find any significant correlation between the gene expression of IL-35 subunits and DAS-28. There was a negative correlation between the plasma levels of neopterin and the gene expression of EBI-3 (p = 0.004). Inversely, we found a positive correlation between plasma level of anti-CCP and neopterin (p < 0.001) also between RF and DAS-28 (p = 0.001).Conclusion: Regarding the significant negative correlation between EBI-3 gene expression and plasma levels of neopterin, it can be concluded that the altered gene expression of EBI-3 may play a role in the pathogenesis of RA.

Impact of vitaminD deficiency on clinical parameters in treatment-naïve rheumatoid arthritis patients.

To determine if patients with rheumatoid arthritis (RA) are at risk of vitaminD deficiency and whether the levels of vitaminD are correlated with clinical parameters in RA. Atotal of 280treatment-naïve RA patients, and 140age- and sex-matched healthy volunteers were enrolled. Serum levels of 1,25-dihydroxycholecalciferol (1,25(OH)2D3), the active form of vitaminD, were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations of 1,25(OH)2D3 less than 25 ng/mL were defined as insufficient. Linear regression was performed to evaluate correlations as (modifying and) confounding factors were controlled. The levels of serum 1,25(OH)2D3 in RA individuals (12.24 ± 6.68 ng/ml) were significantly lower than in healthy controls (21.08 ± 7.14 ng/ml; p < 0.05). An inverse association was found between the levels of 1,25(OH)2D3 and ESR in obese and overweight individuals with RA(βobese = -0.385, βoverweight = -0.395, both p < 0.05), but not in normal and underweight subjects. Asignificant negative association between levels of 1,25(OH)2D3andDAS28score (β = -0.164, p = 0.018) was observed. The levels of 1,25(OH)2D3 were associated moderately and inversely with the absolute numbers of Th-17 (β = -0.158, p = 0.019) and positively with those of CD4+ regulatoryT (Treg) cell (β = 0.146, p = 0.025). The levels of 1,25(OH)2D3 in anti-cyclic citrullinated peptide (anti-CCP)-positive patients with RA were lower than in the anti-CCP-negative RA patients (10.86 ng/ml versus 15.98 ng/ml; t = -3.08, p < 0.01). Asignificant association was observed between levels of vitamin Dand parameters of disease, including body mass index (BMI), DAS28, Th17 cell counts, Treg cell counts, and presence of anti-CCP antibody in RA patients.

Immunological aspects of balneology

The skin is the biggest immune organ of the human body. On the one hand the different mineral waters have strong influence on the skin during the head out water immersion, on the other hand they can casue a lot of molecular changes in the human body, by the modulation of the immune system. On the basis of the available evidence among the inorganic elements the sulphur(and its derivatives) has one of the most pronounced effect on the skin and human body. The sulphurous water can inhibit the production of cytokines,especially IL-2 and interferon gamma (IFN-c) Hydrogen sulphide(H2S) decreases IL-1β-induced activation of fibroblast-like synoviocytes at patients suffering from osteoarthritis, which may have a beneficial effect for its treatment. H2S partially antagonizes IL-1β stimulation through selective manipulation of the MAPkinase. Sulphurous thermal water increases the release of the anti-inflammatory cytokine IL-10 and modulates antioxidant enzyme activity. Sulfur bath therapy could reduce the oxidative stress, by alterations of SOD activities. The radon bath can reduce the activation marker of CD69 on T, B, and NK cells. Radon bath has a beneficial effect on clinical parameters in Rheumatoid arthritis. As account of a new study, it showed for the first time a modulation of the peripheral immune cells following standard radon spa therapy. Mud-bath therapy, can decrease the serum adiponectin and resistin levels at patients after mud bath treatment. Balneotherapy caused statistically significant and long lasting decrease in serum levels of C-reactive protein in patients treated with mineral thermal baths. Long-term bathing in CO2-enriched water proved a cellular protein response of epithelial cells in the epidermis. The heatwater has a possible immunomodulatory effect on keratinocytes during the progression of IL-17-mediated inflammatory skin diseases. Skin Microbiome can change in Patients with Psoriasis before and after Balneotherapy. Thermal stress has an immunosuppressive effect. There are growing numbers of studies when the balneotherapy was combined with anti- TNF therapy, and the results demonstrated that the combined therapy gave better results that the biological therapy alone.

Alterations of Gut Microbiome in Rheumatoid Arthritis

Purpose: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which can cause cartilage and bone damage as well as disability. Recent studies have indicated that the pathogenesis of RA requires the interaction between genetic and environmental factors, such as gut microbiome. However, current evidence for the alterations of gut microbiome in RA is still limited. Thus, our study aimed to analyze the fecal samples from a cohort patient with RA and to identify the associated alterations in gut microbiome when compared to healthy controls. Methods: Fecal samples were obtained from treatment-naïve RA patients (n=50) and healthy controls (n=50). High-quality 16S rDNA V3–V4 sequences were extracted from fecal samples and further sequenced on a 454 Genome Sequencer platform for bioinformatics analysis, resulting in operational taxonomic units (OTUs) related to gut microbiota and phylogenetic tree. Clinical parameters of RA were correlated with specific microbial taxa by Correlation analysis. Results: A total of 121227 OTUs was clustered at 97 % sequence similarity and assigned taxonomic lineages by comparison with the Ribosomal Database Project database. The OTUs were classified into 35 phylums, 73 classes, 143 orders, 280 families, and 1165 genus. Intriguingly, our data revealed a lower alpha diversity, including richness, evenness and Shannon Index, as well as a lower Firmicutes / Bacteroidetes ratio in the gut microbiome of RA patients when compared with the healthy controls (Figure 1a, b). Moreover, at genus level, our taxonomic analysis identified 288 differentially abundant taxa (P< 0.05) (Figure 2a), among which 6 taxa, including Bacteroides, Parabacteroides, Paraprevotella, Porphyromonadaceae, Phascolarctobacterium and Carnobacterium, were significantly enriched in the gut microbiome of RA patients (Figure 2b, c). Conversely, a series of butyrate-producing taxa such as Faecalibacterium, Roseburia, Subdoligranulum, Ruminococcus and Pseudobutyrivibrio were depleted in RA patients but enriched in healthy controls (Figure 2b, c). Furthermore, we found a negative correlation (P<0.05) between the abundance of butyrate-producing Roseburia and the clinical parameters of disease status and activity such as erythrocyte sedimentation rate and the blood level of rheumatoid factors (IgM) (Figure 3). Conclusions: In the present study, we demonstrated that the composition of the gut microbiome in RA patients differed from that in healthy individuals. Our results revealed a decreased microbial diversity accompanied by altered microbial abundance in the gut microbiome of RA patients, which could be characterized as ‘dysbiosis’ and associated with the disease status and activity. The identified alterations in the gut microbiome might provide an updated overview for postulating molecular understandings and therapeutic strategy in RA.Figure 2. Differentially abundant gut microbiome in RA patients. (a) Data of phylogenetic tree analysis to identify differentially abundant taxa. (b) Percentage of 16S reads of major genus of the gut microbiota of RA patients and controls. (c) Quantification of differentially abundant genus of gut microbiome in RA and Control groups.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3. Abundance of Roseburia negatively correlated with the clinical parameters of disease activity in RA patients. Upper pannel: Correlation analysis of the 16S reads number of Roseburia and the erythrocyte sedimentation rate (ESR) in RA patients. Lower pannel: Correlation analysis of the 16S reads number of Roseburia and the blood level of rheumatoid factors (IgM) in RA patients. Note: Pearson rank correlation test was performed to determine correlations in the study variables.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Has the median nerve involvement in rheumatoid arthritis been overemphasized?

Rheumatoid arthritis (RA) is a well and widely recognized cause of carpal tunnel syndrome (CTS). In the rheumatoid wrist, synovial expansion, joint erosions and ligamentous laxity result in compression of the median nerve due to increased intracarpal pressure. We evaluated the published studies to determine the prevalence of CTS and the characteristics of the median nerve in RA and its association with clinical parameters such as disease activity, disease duration and seropositivity. A total of 13 studies met the eligibility criteria. Pooled data from 8 studies with random selection of RA patients revealed that 86 out of 1561 (5.5%) subjects had CTS. Subclinical CTS, on the other hand, had a pooled prevalence of 14.0% (30/215). The cross sectional area of the median nerve of the RA patients without CTS were similar to the healthy controls. The vast majority of the studies (8/13) disclosed no significant relationship between the median nerve findings and the clinical or laboratory parameters in RA. The link between RA and the median nerve abnormalities has been overemphasized throughout the literature. The prevalence of CTS in RA is similar to the general population without any correlation between the median nerve characteristics and the clinical parameters of RA.

O envolvimento do nervo mediano na artrite reumatoide tem sido excessivamente valorizado?

Rheumatoid arthritis (RA) is a well and widely recognised cause of carpal tunnel syndrome (CTS). In the rheumatoid wrist, synovial expansion, joint erosions and ligamentous laxity result in compression of the median nerve due to increased intracarpal pressure. We evaluated the published studies to determine the prevalence of CTS and the characteristics of the median nerve in RA and its association with clinical parameters such as disease activity, disease duration and seropositivity. A total of 13 studies met the eligibility criteria. Pooled data from 8 studies with random selection of RA patients revealed that 86 out of 1561 (5.5%) subjects had CTS. Subclinical CTS, on the other hand, had a pooled prevalence of 14.0% (30/215). The cross sectional area of the median nerve of the RA patients without CTS were similar to the healthy controls. The vast majority of the studies (8/13) disclosed no significant relationship between the median nerve findings and the clinical or laboratory parameters in RA. The link between RA and the median nerve abnormalities has been overemphasized throughout the literature. The prevalence of CTS in RA is similar to the general population without any correlation between the median nerve characteristics and the clinical parameters of RA.

IL17A and IL17F gene polymorphisms in patients with rheumatoid arthritis.

BackgroundInterleukin-17 plays important role in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to examine the associations between polymorphisms in the IL17A and IL17F genes and RA.MethodsWe examined 422 RA patients and 337 subjects as a control group. Single nucleotide polymorphism (SNP) in the IL17A (rs2275913) and IL17F (rs763780, rs11465553, rs2397084) genes were genotyped using TaqMan genotyping assays from Life Technologies Genomic.ResultsThere were no significant differences in distribution of IL17A and IL17F genotypes and alleles between RA patients and control group. There were no significant associations between IL17A and IL17F genotypes and age of disease diagnosis rheumatoid factor, erosive disease as well as extra-articular manifestations.ConclusionsThe results of this study suggest, that IL17A and IL17F gene polymorphism are not the important factors associated with susceptibility and some clinical parameters of RA in a Polish population.

Preferential Induction of the T Cell Auxiliary Signaling Molecule B7-H3 on Synovial Monocytes in Rheumatoid Arthritis

B7-H3, a newly identified B7 family member, has functional duality as a co-stimulator and co-inhibitor that fine-tunes T cell-mediated immune responses. Given that B7-H3 expression on human monocytes and dendritic cells is enhanced by inflammatory cytokines, its potential inmmunoregulatory role at sites of inflammation has been suggested. Further, monocytes play crucial roles in the pathophysiology of various inflammatory disorders including autoimmune diseases; however, the immunological role of B7-H3 in rheumatoid arthritis (RA) has not been defined. Thus, we aimed to investigate the possible roles of monocyte B7-H3 in the pathogenesis of RA. Synovial monocytes, but not peripheral monocytes, in RA patients predominantly express surface B7-H3. The 4Ig isoform of B7-H3 is exclusively induced on the cell surface, whereas the 2Ig B7-H3 isoform is constitutively expressed in the intracytoplasmic region of both peripheral and synovial monocytes. B7-H3 knockdown experiments reveal that surface B7-H3 has an inhibitory effect on IFN-γ production in CD4 memory cells. Moreover, surface B7-H3 expression on synovial monocytes inversely correlates with RA clinical parameters. Our findings demonstrate that activation-induced B7-H3 expression on synovial monocytes has the potential to inhibit Th1-mediated immune responses and immunomodulatory roles affecting RA pathogenesis.

Mental health status can reflect disease activity in rheumatoid arthritis.

A significant number of patients with rheumatoid arthritis (RA) link the start of illness with psychological trauma or severe stress. Impaired mental health (IMH), defined as depression and anxiety with psychoneuroimmunological factors, can play a significant role in RA. The main objective of this research was to investigate the mutual correlation of IMH and RA activity, estimated by the laboratory and clinical parameters in RA patients. An open clinical prospective study that lasted for 6 months was designed. There were 72 patients included, 58 women and 14 men, aged 34 to 80 years and screened for mental health status. The study population was randomized following the Brief Symptoms Inventory (BSI) scale, comprised of 53 questions with a range from 0 (no symptoms) to 4 (severe). This mental test was done only once during the study. Following the results from the BSI scale, RA patients were divided into mentally stable and mentally unstable patients to investigate the influence of RA activity on mental health. The following laboratory and clinical parameters were analyzed: sex, age, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), anti-cyclic citrullinated peptide (anti-CCP) antibody, and disease activity score (DAS28). All RA patients did not express extra-articular manifestations or Sjögren's syndrome. The chi-square test, ANOVA, Pearson's coefficient, and IBM Statistics - SPSS v19 were used. From a total of 72 RA patients, there were 44 mentally stable and 28 mentally unstable patients. All patients had either moderate or severe active disease. The only significant correlation of IMH and activity of RA was found in CRP and DAS28, but no significance was observed in ESR, RF, and anti-CCP. The DAS28 showed high disease activity with an average of 5.3 and CRP of 20.9 mg/L in patients with unstable mental health compared to stable mental health patients, where RA was associated with a moderate DAS average value of 4.35 and CRP of 14.1 mg/L. Depression and anxiety were found in all 28 (39%) RA patients. Mentally unstable RA patients correlate more with severe disease activity, while mentally stable patients express moderate disease activity.

Analyses of Human and Rat Clinical Parameters in Rheumatoid Arthritis Raise the Possibility of Use of Crude Aloe vera Gel in Disease Amelioration

Rheumatoid Arthritis (RA) is a chronic inflammatory condition affecting the joints causing swelling, stiffness and pain which finally leads to substantial loss of functioning and mobility in its advanced stages. In the present study we have monitored important serological parameters of fifty RA patients and also have discussed the justification of using rat as a model for human RA researches by comparing their respective serological parameters. We have also evaluated the anti-arthritic roles of raw Aloe vera gel and its effects in rat model where arthritis was induced by using Freund’s Complete Adjuvant (FCA). Three essential conclusive statements were derived from the study. Firstly, the six clinical parameters that we have selected for the study namely, RA factor, CRP, ASO, ESR, ceruloplasmin and serum creatinine were all essential for the differential diagnosis of Rheumatoid Arthritis during its early and later stages, RA factor being the most sensitive of all parameters (92% sensitivity). Secondly, this study has supported the use of the rat as a model for designing therapeutic strategies against RA. Lastly, as evident from our study, Aloe vera extracts can be beneficial for the reduction of inflammatory edema and also for the reduction of ceruloplasmin in RA condition in rat model. However, further investigations are necessary for more refined therapeutic usage of Aloe vera for the treatment of RA in human.

Elevated CD8+ IL-17+ Tc17 Levels and Their Correlation with Disease Activity in Patients with Rheumatoid Arthritis

Objectives: In this study, we aimed to determine the role of CD8 + IL-17 + double-positive T cells (Tc17) in the pathogenesis and activity of rheumatoid arthritis (RA). Patients and methods: The frequency and distribution of the Tc17 cells were identified using double immunofluorescent staining in peripheral blood mononuclear cells (PBMCs), synovial fluid mononuclear cells (SFMCs), and synovial tissues in RA patients. Soluble interleukin (IL)-17 levels were measured using the enzyme-linked immunosorbent assay (ELISA). Real-time polymerase chain reaction (PCR) was used to determine the IL-17 messenger ribonucleic acid (mRNA) in CD8 + T cells. The correlation between the Tc17 cells and RA clinical parameters, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and Disease Activity Score 28 (DAS 28), a test used for the evaluation of the 28 commonly affected joints in RA, was analyzed. Results: The frequency of Tc17 in the PBMCs of the RA patients was higher compared to the healthy controls. The frequency of Tc17 cells in the SFMCs of the RA patients was also higher than that found in the RA PBMCs and OA SFMCs. The IL-17 mRNA expression in the RA CD8 + T cells was significantly higher than in the healthy controls. The levels of soluble IL-17 in the sera and synovial fluid of the RA patients were significantly higher than those of the healthy control and OA groups. There was a significant positive correlation between the frequency of Tc17 cells in the SFMCs and DAS 28 scores in the RA patients. Conclusion: Our study results strongly demonstrated that a new Tc17 subset existed in RA patients and its frequency was significantly correlated with the disease activity of RA patients. Thus, our study suggests that Tc17 cells along with other IL-17- producing cells, may play an important role in the pathogenesis + IL-17 + T cells; double immunofluorescent staining;