Parameters Of Rheumatoid Arthritis Research Articles

Cytokine profiles and their correlation with clinical and blood parameters in rheumatoid arthritis and systemic lupus erythematosus.

The abnormal biological activity of cytokines and their imbalance are implicated in developing rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Cytokine levels were measured in RA and SLE patients and compared to healthy controls using the Wilcoxon rank sum test and Kruskal-Wallis test. The relationship between cytokine levels and blood and clinical parameters was assessed using Spearman's correlation test. Compared to healthy controls, both RA and SLE patients exhibited elevated levels of GM-CSF, CX3CL1, IFN-α2, IL-12p70, IL-17A, TNF-α, IL-1β, and IFN-γ, which is evidence of their shared inflammatory signature. IL-2 levels were elevated exclusively in RA patients, while MCP-1 and IL-10 were uniquely increased in SLE patients. Notably, TNF-α showed the most significant increase in SLE patients. IL-4 was elevated in SLE patients with nephritis, correlating with IL-6, IL-10, sCD40L, and IL-8, suggesting B cell involvement in lupus nephritis. The negative correlation between CX3CL1 and TNF-α with HDL in RA and SLE respectively, highlights the potential association of these inflammatory markers with cardiovascular risk. These findings underscore the complex cytokine interplay in RA and SLE. CX3CL1 emerges as a potential therapeutic target for RA, while TNF-α and IL-4 show promise as therapeutic targets for SLE.

Hematological Parameters in Rheumatoid Arthritis and their Relationship with Disease Activity

Hematological Parameters in Rheumatoid Arthritis and their Relationship with Disease Activity

Assessment of corneal parameters in patients with rheumatoid arthritis.

To assess the corneal parameters in rheumatoid arthritis (RA) patients. We enrolled 64 patients with RA (32 receiving biologic and 32 receiving conventional drugs) and 32 healthy subjects. Keratometric values (anterior flat [K1], steep [K2], and mean keratometry [Km]), corneal thickness from the pupil center (CCT), apex (ACT), and the thinnest point (TCT), and corneal volume (CV) were measured and compared between the groups. K1, K2, and Km values were significantly higher in the RA group (P = 0.013, P = 0.048, P = 0.027, respectively). The means of CCT, ACT, TCT, and CV were significantly lower in RA patients (P < 0.001, P < 0.001, P < 0.001, P = 0.011, respectively). When we divided RA patients into two groups according to the treatment and compared them to controls, the differences in K1, CCT, ACT, TCT and CV were significant (P = 0.030, P = 0.005, P = 0.001, P = 0.001, P = 0.034, respectively). K1 and CV values of RA-biologic group were similar to the control group (P = 0.205 and P = 0.127, respectively). Biologic agents contribute to the improvement of K1 and CV values in patients with RA.

Association of Serum IL-17 and IL-23 Cytokines With Disease Activity and Various Parameters of Rheumatoid Arthritis in Indian Patients.

Introduction Interleukin-23/T helper 17 (IL-23/Th17) axis cytokine has been thought to be a critical pathway for rheumatoid arthritis (RA) disease development and its association with disease severity, joint erosion, and functional outcome. There is a paucity of data on the role of IL-23/Th17 axis cytokines in an Indian RA subset of patients. We aimed to determinethe association between serum cytokines (interleukin-17 [IL-17] and [IL-23]) and disease activityas well as with clinical and biochemical parameters of RA patients. Methods In this observational cross-sectional study, 84 consecutive RA cases were recruited after obtaining consent. Serum IL-17 and IL-23 levels were measured by the enzyme-linked immunosorbent assay (ELISA) method. Clinical and laboratory parameters, disease activity score 28-erythocyte sedimentation rate (DAS28-ESR), and Health Assessment Questionnaire-II (HAQ-II) were recorded. Correlation of cytokines with various clinical and biochemical parameters was elicited. Results Only C-reactive protein (CRP) correlated positively with IL-23 (rs = 0.26, p = 0.014)but not the ESR. Both IL-17 and IL-23 levels showed an insignificant, weak positive correlation with the disease activity DAS28 (rs = 0.18, p = 0.097; rs = 0.12, p = 0.259, respectively). Neither IL-17 nor IL-23 levels differed among the disease severity group (p = 0.13, p = 0.215). Only the IL-23 level positively correlated with functional status (HAQ-II) (rs = 0.28, p = 0.009). IL-17 level was higher in advanced RA as compared to early RA (p = 0.028). Both IL-17 and IL-23 levels did not vary within the different subgroups (age, obesity, disease-modifying drugs/steroid/biologics use, and serology status). Conclusion Females had higher IL-23 levels than males. Advanced RA had higher IL-17 levels than early RA. The cytokinelevels were not influenced by factors like age, duration of disease, serology status, or drugs. Neither of the cytokines correlated significantly with disease severity. Higher IL-17 levels may have a role in the progression of early non-erosive to chronic erosive arthritis. Higher IL-23 levels may signal a bad functional outcome.

Antiarthritic potential of the butanol fraction of Sesuvium sesuvioides: An in vitro, in vivo, and in silico evaluation.

Sesuvium sesuvioides (Fenzl) Verdc (Aizoaceae) has been traditionally used in the treatment of inflammation, arthritis, and gout. However, its antiarthritic potential has not been evaluated scientifically. The current study was designed to assess the antiarthritic properties of the n-butanol fraction of S. sesuvioides (SsBu) by phytochemical analysis, in vitro and in vivo pharmacological activities, and in silico studies. Phytochemical analysis showed total phenolic contents (90.7 ± 3.02mg GAE/g) and total flavonoid contents (23.7 ± 0.69mg RE/g), and further analysis by GC-MS identified possible bioactive phytocompounds belonging to phenols, flavonoids, steroids, and fatty acids. The in vitro antioxidant potential of SsBu was assessed by DPPH (175.5 ± 7.35mgTE/g), ABTS (391.6 ± 17.1mgTE/g), FRAP (418.2 ± 10.8mgTE/g), CUPRAC (884.8 ± 7.97mgTE/g), phosphomolybdenum (5.7 ± 0.33mmolTE/g), and metal chelating activity (9.04 ± 0.58mg EDTAE/g). Moreover, in the in vitro studies, inhibition (%) of egg albumin and bovine serum albumin denaturation assays showed that the anti-inflammatory effect of SsBu at the dose of 800μg/ml was comparable to that of diclofenac sodium used as a standard drug. The in vivo antiarthritic activity was assessed to determine the curative impact of SsBu against formalin-induced (dose-dependent significant (p < 0.05) effect 72.2% inhibition at 750mg/kg compared to standard; 69.1% inhibition) and complete Freund's adjuvant-induced arthritis (40.8%; inhibition compared to standard, 42.3%). SsBu significantly controlled PGE-2 level compared to the control group (p < 0.001) and restored the hematological parameters in rheumatoid arthritis. Treatment with SsBu significantly reduced oxidative stress by reinstating superoxide dismutase, GSH, and malondialdehyde along with pro-inflammatory markers (IL-6 and TNF-α) in arthritic rats. Molecular docking revealed the antiarthritic role of major identified compounds. Kaempferol-3-rutinoside was found to be more potent for COX-1 (-9.2kcal/mol) and COX-2 inhibition (-9.9kcal/mol) than diclofenac sodium (COX-1, -8.0 and COX-2, -6.5kcal/mol). Out of the 12 docked compounds, two for COX-1 and seven for COX-2 inhibition showed more potent binding than the standard drug. The results from the in vitro, in vivo, and in silico approaches finally concluded that the n-butanol fraction of S. sesuvioides had antioxidant and antiarthritic potential, which may be due to the presence of potential bioactive compounds.

Association of rheumatoid factor and anti-cyclic citrullinated peptide antibody with demographic, clinical, and inflammatory parameters in rheumatoid arthritis

Association of rheumatoid factor and anti-cyclic citrullinated peptide antibody with demographic, clinical, and inflammatory parameters in rheumatoid arthritis

Analysis of the relationship between the response to methotrexate therapy and its pharmacokinetic parameters in rheumatoid arthritis. Sovremennaya Revmatologiya

The development of therapeutic drug monitoring of methotrexate (MT) remains an important and unresolved problem.Objective: to study the dynamics of the concentration of MT metabolites in groups of patients with different responses to MT therapy, to identify the clinical features of these groups.Patients and methods. The study included 79 patients with rheumatoid arthritis (RA), including 65 (82%) women and 14 (18%) men (mean age 53±11 years). MT monoglutamate was measured in erythrocytes (ER) and mononuclear cells (MO), as well as the main MT metabolites: polyglutamates with 2, 3 and 4 glutamate residues (MTPG2-4), as well as 7-hydroxymethotrexate (7-OH-MT) after 4, 12, 24 and 36 weeks after the start of MT treatment.Results and discussion. Among the patients who completed the 24-week follow-up, 34 responded to MT therapy (Group 1) and 36 did not respond to it (Group 2). Patients of the two groups did not differ in the concentration of various metabolites of MT after 4 weeks, age, body mass index, duration of RA, DAS28 value, radiological stage, functional class, presence of extra-articular manifestations, single and cumulative doses of MT. In the 1st group after 12 weeks of therapy, a higher concentration of 7-OH-MT (ER) was detected, after 24 weeks – a higher concentration of 7-OH-MT (MO) and a lower level of MTPH3 (ER).Conclusion. The concentration of 7-OH-MT after 12 and 24 weeks of therapy was higher in the group of patients who responded to therapy. 7-OH-MT appears to be a more persistent metabolite of MT and therefore more applicable for therapeutic drug monitoring of MT. The level of MT and its metabolites (MT monoglutamate, MTPG2 and 7-OH-MT) gradually decreases over time in responders to therapy. A 7-OH-MT concentration of 14.5 nmol/l may be a predictor of a good response to MT therapy.

Qing-Luo-Yin Alleviated Experimental Arthritis in Rats by Disrupting Immune Feedback Between Inflammatory T Cells and Monocytes: Key Evidences from Its Effects on Immune Cell Phenotypes.

BackgroundQing-Luo-Yin (QLY) is an anti-rheumatic herbal formula. Despite the well-investigated therapeutic efficacy of QLY, its immune regulatory properties are largely unknown. CD4+ T cells and monocytes are two key parameters in rheumatoid arthritis (RA). This study investigated the changes in these cells in QLY-treated RA animal models.Materials and MethodsRA models were induced in male SD rats and were orally treated with QLY. Dynamic metabolic changes in collagen-induced arthritis (CIA) rats were monitored by 1H NMR approach. The immunity profiles of CIA and adjuvant-induced arthritis (AIA) rats were evaluated using immunohistochemical, PCR, ELISA, cytokine chip, flow cytometry, and immunofluorescence experiments. The bioactive components in QLY were identified by bioinformatic-guided LC-MS analyses. The compounds with high abundance in QLY decoction and easily absorbed were taken as key anti-rheumatic components and used to treat blood-derived immune cells using in vitro experiments.ResultsThe results indicated that QLY decreased Th17 cells frequency and T cells-released IL-6, IL-17 and GM-CSF in CIA rats, which was attributed to the impaired lymphocyte maturation and altered differentiation. QLY inhibited lactic acid production and inflammatory polarization in the monocytes during the peak period of AIA and CIA. AIA monocytes elicited significant increase in Th17 cells counts, IL-6 and IL-1β secretion in co-cultured splenocytes, which was abrogated by QLY. QLY-containing serum suppressed the phosphorylation of JNK and p65 in AIA lymphocyte-stimulated normal monocytes and consequently inhibited iNOS and IL-1β expression as well as IL-6 and IL-1β production. Matrine, sinomenine and sophocarpine were identified as major bioactive compounds in QLY. These identified compounds effectively inhibited the development of inflammatory T cells using concentrations detected in QLY-treated rats. At higher concentrations (20-fold increase), the chemical stimuli significantly suppressed the production of IL-1β in AIA monocytes by inhibiting JNK and p65 pathways.ConclusionBy targeting inflammatory T cells and monocytes as well as disrupting their interplay, QLY improved immune environment in RA models especially during the active stages of disease.

Evaluation of Liver Function and Lipid profiles in Iraqi patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease with a destructive pattern that affects the joints. It affects the synovial lining tissue of the joints. Females develop rheumatoid arthritis at a higher risk than males. The main treatment for rheumatoid arthritis is disease-modifying anti-rheumatic agents (DMARD) such as methotrexate (MTX) and Etanercept. In this study, ESR, CRP, liver function enzymes, renal function tests and lipid profile were evaluated for rheumatoid arthritis patients. The study includes 120 female patients with rheumatoid arthritis and 60 healthy individuals as a control group with an age range between (20-60) years. The obtained results indicated a significant increase in ESR, CRP activity (p <0.01) in patients compared to the control values. The results also indicated a substantial increase in liver enzymes activity, renal function and lipid profile parameters in rheumatoid arthritis compared to the control values. In conclusion, it appears that DMARD treatment such as methotrexate may be the cause of many complications such as renal impairment. On this basis, we can suggest lowering the weekly dose of methotrexate to patients when effects on liver enzymes activity, renal function, lipid profiles and/or changing treatment when MTX is no longer beneficial.

Association of myostatin, a cytokine released by muscle, with inflammation in rheumatoid arthritis: A cross-sectional study.

Myostatin is a cytokine produced and released by myocytes that might have an outstanding role not only in muscle wasting during cachexia but also in inflammation. Herein we explore the association between myostatin levels and inflammatory parameters in rheumatoid arthritis (RA).One hundred twenty-seven women without rheumatic diseases and 84 women with a diagnosis of RA were assessed in a cross-sectional study. Outcomes reflecting the activity of the arthritis including Disease Activity Score (DAS28-ESR) and impairment in functioning by the Health Assessment Questionnaire-Disability Index were assessed in RA. We obtained Skeletal muscle mass index (SMI), fat-free mass index (FFMI), and fat mass index using dual-energy x-ray absorptiometry. Serum myostatin was determined by enzyme-linked immunosorbent assay. Myostatin levels were correlated with disease activity and parameters of muscle mass.The SMI was lower and concentration of myostatin was higher in RA patients than in controls (P = .008 and P < .001, respectively). Myostatin significantly positively correlated with C-reactive protein (rho = 0.48, P < .001), erythrocyte sedimentation rate (rho = 0.28, P = .009), and DAS28-ESR (rho = 0.22, P = .04), and negatively correlated with SMI (rho = -0.29, P = .008), (FFMI) (rho = -0.24, P = .027). In the multivariate logistic regression analysis, levels of myostatin remained associated with disease activity in RA (P = .027).In our study, myostatin was associated with disease activity in RA patients, suggesting a mechanistic link between myostatin, muscle wasting and inflammation in RA.

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.

PREVALENCE OF 25-HYDROXY VITAMIN D DEFICIENCY AND SOME BIOCHEMICAL PARAMETERS IN IRAQI PATIENTS WITH RHEUMATOID ARTHRITIS AND THEIR ASSOCIATIONS WITH DISEASE ACTIVITY

Objectives: The objectives of the study were to evaluate changes in 25(OH) Vitamin D levels and some biochemical parameters in rheumatoid arthritis (RA) patients compared with healthy controls and assess the correlation of 25-hydroxy Vitamin D, calcium, magnesium, and disease activity. Study the effects of anti-RA drugs on these biochemical parameters and also the role of supplements calcium and 25-OH Vitamin D in RA patients.&#x0D; Methods: This study conducted between 60 patients for RA and 20 healthy controls according to the American College of Rheumatology standards in 2010. In this study, 25-hydroxy Vitamin D was measured using an enzyme-linked immunosorbent assay, and also some biochemical parameters were measured with a spectrophotometer (Humalyzer 2000).&#x0D; Results: Serum 25(OH) Vitamin D, calcium, magnesium, and albumin levels were significantly lower in RA patients compared with healthy controls. Serum alanine aminotransferase aspartate aminotransferase levels were significantly increased in RA patients compared with healthy controls. The correlation was non-significantly among 25-hydroxy Vitamin D and clinical disease activity index (CDAI), while the results showed significantly inverse correlation calcium and magnesium concentrations with CDAI.&#x0D; Conclusion: 25-OH Vitamin D, calcium, albumin, and magnesium deficiency appear to be widespread in patients with RA. Thus, biochemical changes in RA are reflected in the pathogenesis of RA. Furthermore, in these results, there is no relationship between Vitamin D and the disease activity, while there is a relationship between calcium and magnesium with disease activity.

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.

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.

Ultrasound findings in knee osteoarthritis and rheumatoid arthritis compared to MRI

Background: Osteoarthritis is a common musculoskeletal degenerative disease of the cartilage of joints and rheumatoid arthritis is a destructive autoimmune joint disease. The aim of our study was comparing of ultrasound findings in knee osteoarthritis and rheumatoid arthritis with MRI as the gold standard.Methods: One hundred subjects with chronic knee pain referred for knee MRI were evaluated by ultrasound and MRI on the same day. Two radiologists assessed knee osteoarthritis and rheumatoid arthritis parameters on ultrasound and MRI separately and independently. Agreement between the ultrasound and MRI evaluations was determined using weighted kappa statistics. Intra-class correlation coefficients were used to evaluate agreement using the absolute values of knee osteoarthritis and rheumatoid arthritis parameters.Results: The overall agreements between the two expert’s radiologists were 85% for the knee joint. Taking an agreement in US examination of 2 expert’s radiologist the overall k for was 0.69 when comparing assessment of knee osteoarthritis and rheumatoid arthritis parameters between ultrasound and MRI. For the knee joint the overall agreement of US findings with MRI was 89%. The overall sensitivity for US of the knee joint was 95.59%, the overall specificity 81.88% in the detection of knee osteoarthritis and rheumatoid arthritis parameters.Conclusions: Ultrasound assessment of knee osteoarthritis and rheumatoid arthritis parameters is reliable and, showing good diagnostic performance for the detection of knee osteoarthritis and rheumatoid arthritis parameters compared with MRI.

Gray Scale and Power Doppler Ultrasonographic Findings in the Assessment of Disease Activity and Their Correlation with Disease Activity Parameters in Rheumatoid Arthritis.

To study the utility of gray scale and power Doppler ultrasonography in assessing the disease activity and correlation of ultrasonographic findings with disease activity parameters in Rheumatoid Arthritis (RA). This cross-sectional study was conducted on 100 RA patients diagnosed as per 2010 classification criteria. Rheumatoid Factor (RF), serum Anti-cyclic Citrullinated Peptide Antibodies (ACPA), Erythrocyte Sedimentation Rate (ESR), C-reactive Protein (CRP), disease activity score with 28-joint counts and ESR (DAS28-ESR), Visual Analogue Scale (VAS) for global disease activity and Gray Scale Ultrasonography (GSUS) and Power Doppler Ultrsonography (PDUS) scores in hands and wrists were determined. Of 100 RA patients with clinically active arthritis, GSUS detected disease activity in all and PDUS in 95 (95%) patients. Of total 2200 joints assessed, disease activity was seen by clinical assessment in 51.31% (1116/2200), GSUS in 57.36% (1262/2200) and PDUS in 48.36% (1064/2200) joints. For detecting active arthritis, clinical assessment showed 79.5% sensitivity and 76.2% specificity while GSUS showed 100% sensitivity and 82.5% specificity using PDUS as a gold standard. GSUS findings of synovitis, joint effusion and bone erosions and PDUS score showed significant correlations with the swollen joint count, tender joint count, ESR and DAS28- ESR (p<0.05 each) but not with VAS, CRP, RF and ACPA (p>0.05 each). Multivariate analysis showed that swollen joint count was independently associated with synovitis (p=0.029) and tender joint count with PDUS score (p=0.036). GSUS and PDUS findings are useful in ascertaining the disease activity and correlate with clinical disease activity in joints in RA.

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.

Exosomal amyloid A and lymphatic vessel endothelial hyaluronic acid receptor-1 proteins are associated with disease activity in rheumatoid arthritis

BackgroundExosomes are thought to play an important role in exchanging information between cells. The proteins and lipids in exosomes play roles in mediating inflammatory and autoimmune diseases. The aim of this study was to identify exosomal candidate proteins that are related to other inflammatory parameters in rheumatoid arthritis (RA).MethodsThe study population consisted of 60 patients with RA: 30 in the clinical remission (CR) group with a Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) ≤2.6 and 30 in the non-clinical remission (non-CR) group with a DAS28-ESR >2.6. Preparation of exosomes from patient serum samples was performed with the ExoQuick kit, and protein identification/quantification was performed using tandem mass tag labeling/mass spectrometry and an enzyme-linked immunosorbent assay. Comparisons between groups were made using Student’s t test or the Mann-Whitney U test, as appropriate. Spearman’s correlation coefficients (ρ) were calculated.ResultsWe identified six candidate proteins. Exosomal levels of amyloid A (AA) and lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1) differed between the CR and non-CR groups. Both serum and exosomal AA levels were higher in the non-CR group than in the CR group (p = 0.001). Significant positive correlations were found between exosomal AA and C-reactive protein (CRP) as well as between serum AA and CRP (ρ = 0.614, p = 0.001, and ρ = 0.624, p = 0.001, respectively). Although serum levels of LYVE-1 did not differ between the non-CR and CR groups, exosomal levels of LYVE-1 were lower in the non-CR group than in the CR group (p = 0.01). We identified positive correlations between serum/exosomal LYVE-1 and CRP only in the non-CR group (serum ρ = 0.376, p = 0.04; exosome ρ = 0.545, p = 0.002).ConclusionsExosomal LYVE-1 shows potential for use as an additional marker of disease activity in patients with RA, and exosomes may carry other useful markers for RA.

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

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

Comparison of Tear Osmolarity in Rheumatoid Arthritis Patients With and Without Secondary Sjogren Syndrome

To compare tear osmolarity (TO) and other dry eye parameters in rheumatoid arthritis (RA) patients with or without secondary Sjogren syndrome (sSS). Consecutive patients with RA were divided into a sSS group and no-sSS group using conventional diagnostic criteria by rheumatologists using symptomatology, Schirmer test score, and anti-Ro or anti-La autoantibody status. The TO, Ocular Surface Disease Index, dry eye disease (DED) parameters [such as tear breakup time (TBUT) and corneal staining score] and the systemic inflammatory markers [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)] were compared. Correlation analyses between TO and the DED parameters and inflammatory markers were also performed. A total of 42 cases with mean age 54.8 ± 12.3 were included, with 12 patients (29%) having sSS and 30 (71%) without sSS. TO was increased in both groups (329 ± 20 and 319 ± 25 mOsm/L, respectively), but no statistically significant difference was found between the 2 groups (P = 0.126). RA with sSS had significantly shorter TBUT, higher corneal staining score, and ESR CRP levels (P < 0.05). TO did not correlate with the Schirmer test score, but had significant positive correlations with age, corneal staining score, ESR, and CRP levels, and a significant negative correlation with TBUT. TO was increased in RA patients with or without sSS. There was no significant correlation between TO and the Schirmer test score, and the physician could not use TO to diagnose sSS. However, TO correlated well with both DED parameters (TBUT and corneal staining score) and systemic inflammatory markers (ESR and CRP).