Group Of Rheumatoid Arthritis Patients Research Articles

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

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

Periprosthetic joint infections in patients with rheumatoid arthritis are associated with higher complication and mortality rates.

Periprosthetic joint infection (PJI) remains the most devasting complication after total joint arthroplasty (TJA). There has been a significant focus on this topic in recently-published medical literature. However, relatively little has been published about PJI in patients with rheumatoid arthritis (RA), which are often physiologically frail and immunocompromised. A better understanding of PJI in this patient population is therefore crucial. The main aims of this paper are to (1) report complication and mortality rates in a cohort of PJI-RA patients; and (2) clinically characterize them. Medical and surgical records of all RA PJI patients treated surgically from 2003 to 2020 were retrospectively reviewed. Medical history, physical examination, reactive protein (CRP) level, procalcitonin, white blood cell (WBC) count, joint aspiration results, and cultures were used to determine PJI. 54PJIs, 49 of them chronic, were treated in 53RA patients. Mean patient age was 65yrs. (range = 32-88); 33females and 20 males (one bilateral hip). The overall mortality rate was 18.9%(n = 10), with five deaths directly attributed to PJI. Staphylococci accounted for 34 infections (63%), while 11(20.4%) had multiorganism infections and six culture-negative PJI. At the end of treatment 79.6%(n = 43) still had an implanted TJR, 7.4% (n = 4) had spacers, 5.6%(n = 3) had undergone resection arthroplasty, 3.7%(n = 2) arthrodesis, and one each amputation and exarticulation. Mortality and specially complication rates were (are) high in this RA patients group presenting PJI. Delays to diagnosis and treatment may explain some of these poor outcomes. A cohort level III retrospective study.

Whole-Exome Sequencing and Analysis of the T Cell Receptor β and γ Repertoires in Rheumatoid Arthritis.

This study investigated the potential genetic variants of rheumatoid arthritis (RA) using whole-exome sequencing (WES) and evaluated the disease course using T cell receptor (TCR) repertoire analysis. Fourteen patients with RA and five healthy controls (HCs) were enrolled. For the RA patient group, only treatment-naïve patients were recruited, and data were collected at baseline as well as at 6 and 12 months following the initiation of the disease-modifying antirheumatic drug (DMARD) treatment. Laboratory data and disease parameters were also collected. Genetic variants were detected using WES, and the diversity of the TCR repertoire was assessed using the Shannon-Wiener diversity index. While some variants were detected by WES, their clinical significance should be confirmed by further studies. The diversity of the TCR repertoire in the RA group was lower than that in the HCs; however, after DMARD treatment, it increased significantly. The diversity was negatively correlated with the laboratory findings and disease measures with statistical significance. Variants with a potential for RA pathogenesis were identified, and the clinical significance of the TCR repertoire was evaluated in Korean patients with RA. Further studies are required to confirm the findings of the present study.

Clinical and ultrasound features of difficult-to-treat rheumatoid arthritis: A multicenter RA ultrasound cohort study

Objective: The optimal strategy for difficult-to-treat (D2T) rheumatoid arthritis (RA) has not been identified, and the ultrasound characteristics of D2T RA have not been reported. We investigated the clinical characteristics and factors contributing to the outcome in D2T RA in a multicentre RA ultrasound observational cohort. Method: We reviewed 307 Japanese patients diagnosed with RA who underwent treatment with biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). We compared the differences in patient characteristics between the D2T RA and non-D2T RA groups. We examined the factors contributing to a good response [defined as b/tsDMARD continuation and Clinical Disease Activity Index (CDAI) ≤ 10 at 12 months] in the D2T RA patient group. Results: Forty-three patients (14%) were categorized as D2T RA and the remaining 264 (86%) as non-D2T RA at baseline. The grey-scale (GS) score, disease duration, and CDAI at the initiation of treatment were significantly higher in the D2T RA group than in the non-D2T RA group. In contrast, the power Doppler (PD) score was not significantly different between the two groups. Of the 43 D2T RA patients, 20 achieved a good response. The introduction of CTLA4-Ig (n = 5) was significantly associated with a good response in analysis based on inverse probability weighting with propensity score. GS and PD scores at baseline were not significantly associated with therapeutic response at 12 months in D2T RA patients. Conclusions: Patients with D2T RA had high clinical and ultrasound activity and poor responses to treatment with b/tsDMARDs. CTLA4-Ig was associated with a good response at 12 months in D2T RA patients.

Machine learning to characterize bone biomarkers profile in rheumatoid arthritis.

Bone metabolism is disrupted in rheumatoid arthritis (RA); however, the bone metabolic signature of RA is poorly known. The objective of the study is to further characterize the bone metabolic profile of RA and compare it to psoriatic arthritis (PsA), systemic sclerosis (SSc) and healthy controls. We did a cross-sectional case-control study on consecutively enrolled patients and age-matched controls. We collected clinical characteristics, serum biomarkers related to bone metabolism and Bone Mineral Density (BMD). A multiple correlation analysis using Spearman's rank correlation coefficient was conducted within the RA patient group to investigate associations between biomarker levels and clinical variables. Machine learning (ML) models and Principal Component Analysis (PCA) was performed to evaluate the ability of bone biomarker profiles to differentiate RA patients from controls. We found significantly lower BMD in RA patients compared to PsA, and Systemic Sclerosis SSc groups. RA patients exhibited higher Dkk1, sclerostin and lower P1nP and B-ALP levels compared to controls. No significant differences in CTX levels were noted. Correlation analysis revealed associations between bone biomarkers and clinical variables. PCA and ML highlighted distinct biomarker patterns in RA which can effectively discriminated bone biomarkers profile in RA from controls. Our study helped uncover the distinct bone profile in RA, including changes in bone density and unique biomarker patterns. These findings enhance our comprehension of the intricate links between inflammation, bone dynamics, and RA activity, offering potential insights for diagnostic and therapeutic advancements in managing bone involvement in this challenging condition.

Funcionality assessed by the core set of the international classification of functionality and health for rheumatoid arthritis: A cohort study.

The aim of this study was to evaluate the function of a cohort of patients with rheumatoid arthritis (RA) from the core set of the International Classification of Functioning and Health (ICF) for RA over 12 months. We used prospective longitudinal data to conduct a cohort study among a well-characterized group of RA patients. Ninety RA patients aged between 40 and 70 years were included in the study. Patients were evaluated at baseline and after 12 months. Age, disease duration, current smoking, erosions, disease activity, functional test, disability and physical activity were evaluated. Then, the ICF core set classification for RA was applied. 81 patients completed the assessments, the majority of patients were female (88.9%) and the mean age was 56.5 ± 7.3 years. At baseline, the median disease activity was 3.0. There was a statistically significant (p < 0.02) improvement in "Exercise tolerance functions" over 12 months and also a statistically significant (p < 0.001) decrease in "Muscle strength functions" over 12 months. The activity and participation domain showed a weak correlation with the clinical data of the DAS28-PCR (p<0.02). We conclude that relevant aspects of the ICF Core Set for RA were able to adequately express the physical and functional factors of the RA cohort. This tool provides a common language for the interdisciplinary team, which can enhance the use of timely interventions to prevent physical disability in clinical practice.

Evaluating the expression level of genes related to autophagy in rheumatoid arthritis patients.

Rheumatoid arthritis or joint rheumatism is the most common systemic inflammatory disease of the joints and is considered one of the chronic autoimmune diseases. T cells and other immune cells are called to the synovial tissue and cause this disease to progress. Autophagy is a process that is associated with the breakdown of intracellular organelles. As a regulator of cell homeostasis, it can affect the activation of immune cells and participate in the pathogenesis of rheumatoid arthritis. This study aimed to evaluate the gene expression level of autophagy genes in two groups of rheumatoid arthritis patients and healthy individuals. For this purpose, peripheral blood was obtained from two groups of people, including 40 rheumatoid arthritis patients, and 40 healthy individuals. The expression of two genes related to autophagy, Atg5, and Beclin-1, was evaluated in peripheral blood cells using the real-time PCR method. The results showed that the expression of the Beclin-1 gene increased by 2.21 times in rheumatoid arthritis patients compared to healthy individuals (P = 0.024). The expression of the Atg5 gene in rheumatoid arthritis patients increased by 1.53 times compared to healthy subjects (P = 0.041). In general, this study showed that in rheumatoid arthritis patients, increased expression of autophagy genes could be involved in the pathogenesis of this disease. In other words, the findings showed that reducing autophagy can reduce the severity of the disease in people with rheumatoid arthritis.

Comparison of Plasma Levels of MicroRNA-155-5p, MicroRNA-210-3p, and MicroRNA-16-5p in Rheumatoid Arthritis Patients with Healthy Controls in a Case-control Study.

Rheumatoid arthritis is a chronic autoimmune disease that causes inflammation and destruction of the joints. The objective of the current study was to evaluate the expression of microRNA (miR)-155-5p, miR-210-3p, and miR-16-5p in the plasma of patients with rheumatoid arthritis in comparison with a healthy control group to attain an expression profile for earlier diagnosis and treatment. To carry out this study, 100 individuals were chosen as two equally sized groups of rheumatoid arthritis patients and healthy controls. Five milliliters of blood were drawn from each individual, and plasma RNA was extracted using Trisol solution. Complementary DNAs were synthesized using the Moloney leukemia virus (MMLV) and deoxynucleoside triphosphate (dNTP). Finally, real-time polymerase chain reaction (PCR) was implemented using the SYBR Green kit. The mean expression of miR-155-5p, miR-210-3p, and miR-16-5p were 2.46±2.79, 1.97±1.90, and 69.62±88.44 in the rheumatoid arthritis group, and 0.34±0.33, 9.82±9.34, and 7.94±7.09 in the healthy group, respectively. Additionally, significant differences were revealed in the relative expression of the selected microRNAs in 4 subgroups of rheumatoid arthritis patients with different disease activities based on the disease activity score 28 (DAS28). ROC curve analysis showed that miR-155-5p (area under the curve, AUC=0.90, sensitivity=80%, specificity=81%), miR-210-3p (AUC=0.75, sensitivity=66%, specificity=71%), and miR-16-5p (AUC=0.96, sensitivity=89%, specificity=82%) could be potential biomarkers for rheumatoid arthritis diagnosis. Increased expressions of miR-16-5p and miR-155-5p and decreased expression of miR-210-3p in rheumatoid arthritis patients compared with healthy individuals demonstrate the effectiveness of these microRNAs in disease incidence and progression. Thus, the expression levels of these microRNAs can be used for diagnostic and therapeutic purposes.

Serum Cytokine Profiles in Patients with Rheumatoid Arthritis Before and After Treatment with Methotrexate.

Rheumatoid arthritis (RA) is an inflammatory autoimmune illness affecting around 1% of the population globally. Cytokines have a crucial role in the pathogenesis of RA. The objectives of the present study were to compare the serum cytokine profiles between methotrexate (MTX)-treated and MTX-naive RA patient groups, MTX-treated RA patient group and healthy controls, and MTX-naive RA patient group and healthy controls. Enzyme linked immunosorbent assay (ELISA) kits were used to quantify the serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-17, IL-6, interferon-gamma (IFN-γ), and IL-10 in 80 RA patients (48 MTX treated and 32 MTX naive) and 80 healthy controls. For all cytokine assays, absorbance was measured at 450 nm using a microplate reader (Bio-Rad). Independent sample t-test was used to compare the serum cytokine concentrations between the study groups using SPSS version 25. MTX-treated RA patient group had significantly reduced serum levels of TNF-α (36.13 ± 17.64 versus 45.82 ± 23.07, *P = 0.037), IL-17 (307.85 ± 151.74 versus 435.42 ± 241.19, **P = 0.006), and IFN-γ (414.93 ± 212.13 versus 527.15 ± 269.61, *P = 0.041) compared to MTX-naive RA patients. Both MTX-treated and MTX-naive RA patient groups had significantly high serum levels of TNF-α, IL-1β, IL-17, IL-6, IFN-γ, and IL-10 when compared to healthy controls (***P < 0.001). Downregulation of the serum concentrations of certain key cytokines, viz. TNF-α, IL-17, and IFN-γ, demonstrates the anti-inflammatory effect of MTX in RA patients.

Proteomics analyses of human plasma reveal triosephosphate isomerase as a potential blood marker of methotrexate resistance in rheumatoid arthritis.

The objective of this study was to assess differentially expressed blood proteins between patients with active RA and patients in remission after MTX treatment, with the aim of identifying a biomarker of MTX resistance (MTXR). Two populations of RA patients treated with a stable dose of s.c. MTX for at least 3 months were constituted according to the DAS28: remission (DAS28 < 2.6; n = 24) and active disease (DAS28 > 3.2; n = 32). The two groups of RA patients were homogeneous regarding their epidemiological characteristics, except for the duration of treatment, which was longer in the remission group. After collection of a blood sample, plasma protein digestion was performed, followed by untargeted proteomics analysis. Then, a targeted analysis was performed to confirm the results of the untargeted approach. Untargeted proteomics analysis revealed eight plasma proteins that were differentially expressed between the two groups of patients. Among them, triosephosphate isomerase (TPI-1) and glucose-6-phosphate isomerase (GPI), which are main actors in glycolysis, were found down-regulated in the active group. This result was confirmed for TPI-1 in the targeted proteomics analysis. A first step was achieved in the search for biomarkers of MTXR, with the identification of two actors in glycolysis (TPI-1 and GPI). The next step will be to confirm these results in a larger cohort, including samples from treatment-naive patients, to assess the predictive potential of these protein markers.

Preclinical Characterization of Pharmacologic NAD+ Boosting as a Promising Therapeutic Approach in Rheumatoid Arthritis.

We analyzed NAD+ metabolism in patients with rheumatoid arthritis (RA), its association with disease activity and clinical outcomes of RA, and the therapeutic potential of pharmacologic NAD+ boosting. Our study included 253 participants. In the first cohort, comprising 153 RA patients and 56 healthy donors, we assessed NAD+ levels and NAD+ -related gene pathways. We analyzed 92 inflammatory molecules by proximity extension assay. In the second cohort, comprising 44 RA patients starting anti-tumor necrosis factor (anti-TNF) drugs, we evaluated changes in NAD+ levels and their association with clinical response after 3 months. Mechanistic studies were performed ex vivo on peripheral blood mononuclear cells (PBMCs) from patients with RA to test the beneficial effects of NAD+ boosters, such as nicotinamide and nicotinamide riboside. Reduced NAD+ levels were found in RA samples, in line with altered activity and expression of genes involved in NAD+ consumption (sirtuins, poly[ADP-ribose] polymerase, CD38), transport (connexin 43), and biosynthesis (NAMPT, NMNATs). Unsupervised clustering analysis identified a group of RA patients with the highest inflammatory profile, the lowest NAD+ levels, and the highest disease activity (as shown by the Disease Activity Score in 28 joints). NAD+ levels were modulated by anti-TNF therapy in parallel with the clinical response. In vitro studies using PBMCs from RA patients showed that nicotinamide riboside and nicotinamide increased NAD+ levels via NAMPT and NMNAT and reduced their prooxidative, proapoptotic, and proinflammatory status. RA patients display altered NAD+ metabolism, directly linked to their inflammatory and disease activity status, which was reverted by anti-TNF therapy. The preclinical beneficial effects of NAD+ boosters, as shown in leukocytes from RA patients, along with their proven clinical safety, might pave the way for the development of clinical trials using these compounds.

Antibodies to cyclic citrullinated peptide and angiopoietin-like protein type 4 as markers of immune inflammation and osteoporotic processes in rheumatoid arthritis patients

Low-energy fractures in rheumatoid arthritis (RA) are more common in patients with high activity and long duration of disease, and with high titers of anti-citrullinated antibodies (ACPA). Increased expression of angiopoietin-like protein type 4 (ANGPTL4) in bone tissue has also been noted in inflammatory arthritis. The purpose of the present study was to analyze the effect of ACPA and ANGPTL4 on systemic bone mineral density in RA patients. Antibodies to ACPA and ANGPTL4 content were detected in blood serum of 96 RA patients (women, 91.7%) by enzyme immunoassay. Mineral density of the lumbar vertebrae (BMDL1-L4), hip neck, and entire femur (BMDtotal) was measured by dual-energy X-ray absorptiometry (DXA). In study group, the ACPA and ANGPTL4 tests were positive in 61.5% and 41.7% of patients, respectively. Negative correlations were shown between ACPA and BMDtotal, and of ANGPTL4 with BMDL1-L4 (p &lt; 0.05). Separation of the patients into groups with low (n = 34) and high (n = 62) DAS28 activity demonstrated a significant increase in ACPA with increasing RA activity (p = 0.042). ACPA and ANGPTL4 scores were also significantly higher in the group of 45 RA patients with osteoporosis (OP) compared to the RA group without OP (n = 51) showing significant difference at p = 0.002 and p = 0.028, respectively. Patients’ age, body mass index (BMI), duration and activity of the disease had no significant effect on ACPA in the general group of RA patients. However, the correlation between ACPA and DAS28 proved to be significant in the group of RA patients with OP (b = 0.31, p = 0.039). Among all presented variables, the disease duration was the only significant factor for ANGPTL4 in the total group of RA patients (b = 0.31, p = 0.039). In the regression model, BMDtotal showed similar correlations with patients’ age (b = -0.28), BMI (b = 0.25), and ACPA level (b = -0.26). A search for association between BMDL1-L4 and various RA characteristics demonstrated a strong correlation with ANGPTL4 only (b = -0.74; R2 = 0.57). The revealed correlation between ANGPTL4 and decreased BMD specifically in the spongy layer of bone allows us to identify the RA patients with high ANGPTL4 levels as a risk group specifically for spinal fractures thus considering ANGPTL4 as a potential target for treatment of osteoporotic disorders.

Chromosomal radiosensitivity in oncological and non-oncological patients with rheumatoid arthritis and connective tissue diseases

BackgroundThe risk of developing late radiotoxicity after radiotherapy in patients with high chromosomal radiosensitivity after radiotherapy could potentially be higher compared to the risk in patients with average radiosensitivity. In case of extremely high radiosensitivity, dose reduction may be appropriate. Some rheumatic diseases (RhD), including connective tissue diseases (CTDs) appear to be associated with higher radiosensitivity. The question arises as to whether patients with rheumatoid arthritis (RA) also generally have a higher radiosensitivity and whether certain parameters could indicate clues to high radiosensitivity in RA patients which would then need to be further assessed before radiotherapy.MethodsRadiosensitivity was determined in 136 oncological patients with RhD, 44 of whom were RA patients, and additionally in 34 non-oncological RA patients by three-colour fluorescence in situ hybridization (FiSH), in which lymphocyte chromosomes isolated from peripheral blood are analysed for their chromosomal aberrations of an unirradiated and an with 2 Gy irradiated blood sample. The chromosomal radiosensitivity was determined by the average number of breaks per metaphase. In addition, correlations between certain RA- or RhD-relevant disease parameters or clinical features such as the disease activity score 28 and radiosensitivity were assessed.ResultsSome oncological patients with RhD, especially those with connective tissue diseases have significantly higher radiosensitivity compared with oncology patients without RhD. In contrast, the mean radiosensitivity of the oncological patients with RA and other RhD and the non-oncological RA did not differ. 14 of the 44 examined oncological RA-patients (31.8%) had a high radiosensitivity which is defined as ≥ 0.5 breaks per metaphase. No correlation of laboratory parameters with radiosensitivity could be established.ConclusionsIt would be recommended to perform radiosensitivity testing in patients with connective tissue diseases in general. We did not find a higher radiosensitivity in RA patients. In the group of RA patients with an oncological disease, a higher percentage of patients showed higher radiosensitivity, although the average radiosensitivity was not high.

The Protective Effect of HLA-DRB1 and HLA-DQB1 Alleles to ACPA-Positive and RF-Positive RA in Albanian Population

BACKGOUND: The prevalence of rheumatoid arthritis (RA) and its specific autoantibodies varies in different populations. This variability depends on the genetic polymorphism of the immune response genes among which the HLA system plays a major role. AIM: We conducted a preliminary study of the distribution of HLA-DRB1 and HLA-DQB1 first field level alleles in a sample of 100 Albanian patients with RA. METHODS: In this context, we studied the HLA-DRB1 and HLA-DQB1 first-level allele frequencies in 100 Albanian patients with RA and considering their rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) serologic subgroups. We compared them with the respective frequencies in a population of 191 Albanian individuals without known pathology. RESULTS: No differences were found between the controls and the RA patient group, but three statistically significant differences were found: an increase in DRB1*04 among ACPA-positive, RF-positive and ACPA-positive/RF-positive patients, a significant decrease in DRB1*11 among ACPA-positive/RF-positive, and also a decrease in DRB1*13 among RF-positive patient subgroups. The frequencies of DRB1 allotypes in ACPA+ and RF+ patients compared to their counterpart ACPA− and RF−patient subgroups showed the predisposing effect of HLA-DRB1*04 for ACPA and RF seropositivity (p, respectively, 0.0008 and 0.0017) and the protective role of HLA-DRB1*11 for ACPA and RF positivity (p, respectively, 0.007 and 0.02). The same protective role from the RF positivity is also found with the HLA-DRB1*13 alleles (p = 0.007). As far as the DQB1 locus is concerned, a protective association has been found between the HLA-DQB1*06 alleles with both RF+ and RF+ ACPA+ positivity (p, respectively, 0.05 and 0.04) when comparing the control group with the respective RA patient subgroups. In ACPA+ and RF+ patients compared to the ACPA− and RF− patient subgroups, the only detected difference was between RF (+) and RF (−) patients (p =0.04). CONCLUSION: The relatively low frequencies of DRB1*04 and high (DRB1*11 and DRB1*13) in the Albanian population might explain the rather low positivity rate of ACPA and RF antibodies among the Albanian RA patients. Our study demonstrates that DRB1*11, DRB1*13 and DQB1*06 may be negatively associated with RA. Conversely, DRB1*04 may confer susceptibility to RA in Albanian population.

Peculiarities of immunological manifestations in patients with rheumatoid arthritis in the presence of chronic infection with &lt;i&gt;Helicobacter pylori&lt;/i&gt; variant encoding cytotoxin-associated gene A

The study aimed to evaluate the association between cyclic citrullinated peptide antibody seropositivity and chronic Helicobacter pylori (H. pylori) infection in patients with rheumatoid arthritis (RA). We examined 92 women with moderate RA activity. Serum antibodies to cyclic citrullinated peptide (antiCCP), antibodies to H. pylori (anti-H. pylori-IgG), and total antibodies to H. pylori CagA antigen (antiCagA) were determined by enzyme immunoassay; the presence of anti-CagA-IgG positivity was confirmed by immunoblot. 68.5% of RA patients were positive for anti-H. pylori-IgG, and 44.4% of patients in this group were positive for anti-CagA-IgG. All the study participants were divided into three groups: I – H. pylori seronegative (H. pylori- ); II – H. pylori positive, CagA negative (H. pylori+/CagA- ); III – H. pylori positive and CagA positive (CagA+). The anti-CCP values in RA patients with CagA+ (group III) were significantly higher not only in comparison with patients seronegative for H. pylori (p &lt; 0.001), but also in comparison with patients from group II (H. pylori+/CagA- ) (p = 0.041). A study of the influence of the RA activity, the presence of RF and H. pylori on anti-CCP content demonstrated a small proportion of anti-CCP variability (R2 = 0.09), with a high contribution of H. pylori (beta = 0.25). The addition of the CagA(+) index (beta = 0.503) to the presented model allowed us to describe the variability of anti-CCP in almost 30% of cases (R2 = 0.29). In the group of RA patients with anti-CCP values exceeding the established threshold value of 20 U/mL (normal index), there was an increase in the proportion of patients infected with H. pylori (p &lt; 0.001), but not the proportion of CagA-positive patients (p = 0.06). When the threshold level was increased to 60 U/mL (three times the upper limit of normal) in patients with significantly high anti-CCP, the association with positivity for CagA became significant (p = 0.005). CagA is highly immunogenic and is capable of inducing an inflammatory response in the host that goes beyond the effect of H. pylori itself. Additional experimental studies are needed to investigate possible clinical and laboratory associations that may influence the treatment tactics of CagA+ patients with RA who are seropositive for anti-citrullinated antibodies, as well as to evaluate the possible effects of therapeutic intervention aimed at the eradication of H. pylori in this group.

The role of regulatory micro-RNAs in inflammatory processes and production of tumor necrosis factor-alpha in patients with rheumatoid arthritis

Background. Micro-RNAs are fundamental agents of post-transcriptional control of gene expression. In recent years many works have appeared on the possible role of micro-RNAs in rheumatoid arthritis (RA). Studies of the role of micro-RNA and the relationship with the synthesis of tumor necrosis factor-α (TNF-α) are very promising for understanding the pathogenesis and treatment of RA and other autoimmune diseases. The purpose of the research was to study the role of regulatory micro-RNAs in inflammatory processes and the possible connection with the production of TNF-α in patients with RA. Materials and methods. 29 patients with active RA and 20 healthy individuals (control) were examined. All subjects were examined for 16 micro-RNAs. The choice of micro-RNA was based on previous studies and theoretical conclusions (according to the miRWalk database). Rheumatoid factor, the level of antibodies to cyclic peptides containing citrulline, C-reactive protein (СRP), levels of TNF-α (serum, spontaneous, and stimulated) were determined in the blood of patients. Results. Statistical analysis demonstrated significant overexpression of miR-221, miR-203, miR-146b, miR-132, miR-21 and miR-17-3p and inhibition of miR-223 synthesis in RA patients. The activation of TNF-α synthesis at rest and the increased production of TNF-α by mononuclear cells after stimulation in RA were shown. Differences in the levels of relative expression of some micro-RNAs between seropositive and seronegative groups of RA patients were found, but only hyperexpression of miR-155 was highly reliable. For the first time, a possible relationship between TNF-α production and miR-29 and miR-155 micro-RNAs, as well as a correlation between miR-16, miR-99b and miR-203 and CRP levels, was revealed. Conclusions. The obtained data on the profile of micro-RNAs in RA makes it possible to distinguish the most “interesting” micro-RNAs for further study of pathogenesis, their role in inflammation, to study the choice of TNF-α inhibitors, and predicting the effectiveness of that treatment.

Socioeconomic, Disease-Related, and Personal Factors Associated With Participation in Remote Follow-Up in Rheumatoid Arthritis: A Cross-Sectional Study.

To identify socioeconomic, disease-related, and personal factors associated with participation in remote follow-up in patients with rheumatoid arthritis (RA). Following the implementation of a patient-reported outcome-based remote follow-up intervention in RA patients in Denmark, a cross-sectional study was conducted among 775 prevalent patients. In 2019, an electronic questionnaire was sent to eligible RA patients, covering health literacy and patient experience regarding involvement and confidence with remote care. Questionnaire data were linked to nationwide registries regarding socioeconomic status, labor market affiliation, and comorbidity level. Associations between registry- and questionnaire-based factors and remote follow-up were analyzed using multiple logistic regression analysis. All 775 patients were included in the registry-based analyses, but only 394 of 646 (61%) completed the questionnaire. No attachment to the labor market or low household income was associated with lower odds of remote follow-up participation (odds ratio [OR] 0.53 [95% confidence interval (95% CI) 0.34-0.83]) and (OR 0.69 [95% CI 0.48-1.00]). Further, a high level of comorbidity was associated with lower odds of remote follow-up participation compared to a low/medium level of comorbidity (OR 0.53 [95% CI 0.34-0.81]). No association was found between health literacy and remote follow-up, but remote follow-up attendees reported more confidence in remote care (OR 1.33 [95% CI 1.21-1.47]). Participation in remote follow-up was associated with attachement to the labor market, household income, degree of comorbidity, and confidence with remote care. Additional research is necessary to investigate whether a larger and more divergent group of RA patients should be considered for inclusion in remote follow-up programs.

Rheumatoid arthritis and the proinflammatory cytokine IL-17.

Rheumatoid arthritis (RA) is the most common inflammatory joint disease. Various proinflammatory cytokines are involved in the pathogenesis of this chronic disorder. It is characterized by the presence of autoantibodies, such as rheumatoid factor and antibodies against citrullinated peptides. The present study focuses on investigation of possible association between the proinflammatory cytokine interleukin 17 and anti-CCP, anti-MCV, and anti-CarP antibodies seropositivity in RA patients. To assess serum levels of interleukin 17 (IL-17) in patients with rheumatoid arthritis and healthy controls (HC) and to investigate the relationship between IL-17 and anti-cyclic citrullinated protein (anti-CCP) antibodies, antimutated citrullinated vimentin (anti-MCV) antibodies, and anti-carbamylated protein (anti-CarP) antibodies in patients with RA. Forty-seven patients diagnosed with rheumatoid arthritis and 44 healthy controls were included in the study. Serum IL-17 levels were examined in all participants. Anti-CCP, anti-MCV, and anti-CarP antibodies were tested in the group of RA patients. The mean serum level of IL-17 in RA patients was higher (12.8pg/ml) than that in healthy controls (7.9pg/ml), but the difference was not statistically significant (p=0.276). No significant correlation was observed between anti-CCP (+/-) and IL-17 (rs=0.162, p=0.380), and between anti-MCV (+/-) and IL-17 (rs=0.157, p=0.340). A significant positive correlation of moderate value was reported between anti-CarP (+/-) and IL-17 (rs=0.388, p=0.015). The present study demonstrated that the IL-17 serum levels in RA patients were increased compared to healthy controls. No correlation was found between ACPA immunological markers and IL-17 levels in patients with RA. A positive correlation was found between anti-CarP antibodies and IL-17 in the patients' group. The increased level of IL-17 is suggestive of its possible role in the pathogenesis of CarP positive RA patients.

Prothrombotic state in rheumatoid arthritis

Aim. To study the indices of standard coagulogram and thrombodynamics test in native plasma and in the test with phospholipids in relation to the activity of rheumatoid arthritis (RA) and the ongoing therapy.Material and methods. We examined 28 patients with rheumatoid arthritis and eight age- and sex-matched healthy controls: 11 patients with high rheumatoid arthritis activity (DAS28&gt;5.2) (Group 1), nine patients with low and moderate rheumatoid arthritis activity (DAS28&lt;5.2) (Group 2) and eight rheumatoid arthritis patients receiving anticoagulants (Group 3). Results. Elevated fibrinogen was more common in the RA patient groups: 5/11(45%) in group 1, 3/9(33%) in group 2 and 3/8(38%) in group 3. In the control group, fibrinogen was normal, p&gt;&lt;0.05. Increased SFMC was found in all patients in all three groups (100%) and only in 2 of the controls (25%), with p&gt;&lt;0.05. Mean clot density was significantly higher in RA groups than in controls: 26811, 25437 and 24740 versus 20631 c.u. in groups 1, 2, 3 and control, respectively, p&gt;&lt;0,01. In patients with anticoagulants, lag time (1.4 minutes) was longer than without anticoagulants (1.1-1.2 minutes), with p&gt;&lt;0.05 in all cases. Spontaneous clots were detected only in patients: 3 in groups 1 and 1 each in groups 2 and 3. Hypocoagulation was detected only in group 3 in 1/8(12%) patients, and thrombotic readiness status was detected in groups 1 and 2: in 2/11(18%) and 1/9(11%) patients, respectively. The frequency of normal- and hypercoagulation did not differ between the patient and control groups. Conclusion. According to the thrombodynamics test, hypercoagulability is present in RA patients. Thrombodynamics test can be used to identify the risk of thrombosis and to individualize therapy in RA patients. Keywords: prothrombotic state, hypercoagulation, rheumatoid arthritis, thrombodynamics&gt;˂ 5.2) (Group 2) and eight rheumatoid arthritis patients receiving anticoagulants (Group 3).Results. Elevated fibrinogen was more common in the RA patient groups: 5/11(45%) in group 1, 3/9(33%) in group 2 and 3/8(38%) in group 3. In the control group, fibrinogen was normal, p˂ 0.05. Increased SFMC was found in all patients in all three groups (100%) and only in 2 of the controls (25%), with p˂ 0.05. Mean clot density was significantly higher in RA groups than in controls: 26811, 25437 and 24740 versus 20631 c.u. in groups 1, 2, 3 and control, respectively, p˂ 0,01. In patients with anticoagulants, lag time (1.4 minutes) was longer than without anticoagulants (1.1-1.2 minutes), with p˂ 0.05 in all cases. Spontaneous clots were detected only in patients: 3 in groups 1 and 1 each in groups 2 and 3. Hypocoagulation was detected only in group 3 in 1/8(12%) patients, and thrombotic readiness status was detected in groups 1 and 2: in 2/11(18%) and 1/9(11%) patients, respectively. The frequency of normal- and hypercoagulation did not differ between the patient and control groups.Conclusion. According to the thrombodynamics test, hypercoagulability is present in RA patients. Thrombodynamics test can be used to identify the risk of thrombosis and to individualize therapy in RA patients.

Analysis of IGH allele content in a sample group of rheumatoid arthritis patients demonstrates unrevealed population heterogeneity.

Immunoglobulin heavy chain (IGH) germline gene variations influence the B cell receptor repertoire, with resulting biological consequences such as shaping our response to infections and altering disease susceptibilities. However, the lack of information on polymorphism frequencies in the IGH loci at the population level makes association studies challenging. Here, we genotyped a pilot group of 30 individuals with rheumatoid arthritis (RA) to examine IGH allele content and frequencies in this group. Eight novel IGHV alleles and one novel IGHJ allele were identified in the study. 15 cases were haplotypable using heterozygous IGHJ6 or IGHD anchors. One variant, IGHV4-34*01_S0742, was found in three out of 30 cases and included a single nucleotide change resulting in a non-canonical recombination signal sequence (RSS) heptamer. This variant allele, shown by haplotype analysis to be non-expressed, was also found in three out of 30 healthy controls and matched a single nucleotide polymorphism (SNP) described in the 1000 Genomes Project (1KGP) collection with frequencies that varied between population groups. Our finding of previously unreported alleles in a relatively small group of individuals with RA illustrates the need for baseline information about IG allelic frequencies in targeted study groups in preparation for future analysis of these genes in disease association studies.