Variant Of Rheumatoid Arthritis Research Articles

Clinical Features of ACPA-Negative and ACPA-Positive Variants of Rheumatoid Arthritis.

: The study included patients with a reliable diagnosis of rheumatoid arthritis (RA) according to the criteria of ACR/EULAR 2010. Depending on the ACPA values, two groups of patients were recruited: ACPA-positive and ACPA-negative, comparable in gender, age, duration of the disease, and therapy. The nature of the onset and course of the disease and the activity of RA were evaluated (according to the DAS28, SDAI, CDAI indices). : The study involved 79 patients with ACPA-negative variant of RA and 79 ACPA-positive patients. The age of patients (Me [IR] (in years)) with the ACPA(-) variant was 52 [39; 62]; with the ACPA(+) variant, 54 [42; 62]; the duration of the disease (in months) was 59 [23; 122] and 48 [17; 84], respectively. In ACPA(+) patients, a higher disease activity was determined (by the indices DAS 28crp, DAS28esr, SDAI, CDAI), higher values of C-reactive protein and erythrocyte sedimentation rate, and a greater number of painful and swollen joints (p < 0.05). According to the localization of the involved joints, arthritis of the proximal interphalangeal, metacarpal, wrist and shoulder joints was more often determined in ACPA(+) patients. Systemic manifestations of RA at the time of examination and in the anamnesis were statistically significantly more common in ACPA(+) (32.9%) than in ACPA(-) (17.7%) patients. Of the systemic manifestations, rheumatoid nodules were more common in ACPA(+) patients, whereas a tendency to a higher frequency of neuropathy, sclerites, and episcleritis was revealed in ACPA(-) patients. . In patients with ACPA(-) subtype, clinical signs of joint damage and the inflammatory component are less pronounced compared to ACPA(+). However, the mixed picture of manifestation, the less "bright" course of the disease, the absence of characteristic immunological biomarkers necessitate long-term and careful monitoring of this group of patients. At the same time, the subjective severity of the disease and dysfunction due to ankylosing joints do not differ from the ACPA(+) variant of RA.

Is there a “renal-pulmonary syndrome” in rheumatoid arthritis?

Objective: to compare the course of “rheumatoid disease” in multimorbid patients with and without interstitial lung disease (ILD).Material and methods. Two groups were formed of 1034 patients with active rheumatoid arthritis (RA) who met the 2010 ACR/EULAR criteria: one group with ILD identified by high-resolution computed tomography of the lungs (n=82) and another – without ILD (n=900). In all patients, estimated glomerular filtration rate (eGFR) was determined using the Cockroft–Gault formula. The presence and stage of chronic kidney disease (CKD) was assessed depending on the eGFR level: stage I CKD was diagnosed in eGFR &lt;89 ml/min, stage II (subclinical) – 60&lt;eGFR &lt;89 ml/min, stage IIIa (clinical) – 45&lt;eGFR&lt;59 ml/min and IIIb – 30&lt;eGFR&lt;45 ml/min.Results and discussion. Arterial hypertension (p=0.004), cerebrovascular disease (p=0.0001), diabetes mellitus (p=0.04), obesity, psoriasis (p=0.009) and stage II–III CKD (p=0.04) were more frequently observed in the group with ILD.Conclusion. The combination of CKD and ILD frequently found in patients with RA and the known similarity and close interrelationship of the pathogenesis of these diseases, suggest a type of “renal-pulmonary syndrome” associated with a specific variant of RA.

Role of miRNA Let-7 in Plasma of Rheumatoid Arthritis.

Objectives: Micro ribonucleic acids (miRNAs) are noncoding RNAs, recently implicated as potential biomarkers or therapeutic targets for autoimmune diseases such as rheumatoid arthritis (RA). The aim of this study is to assess the role of miRNA Let-7 in the plasma of RA. Materials and methods: Trained medical staff already enrolled for the study collected blood samples from healthy controls (N = 42) and RA patients (N = 44). In the laboratory, these samples were centrifuged at 2000 rpm for 8 minutes to separate serum from the sample, which was then transferred to a plain vial. Until transport to the genetic lab, samples were stored at -20°C Deoxyribonucleic acid (DNA) was isolated using a standard protocol cohort of controls and patient blood samples. Quantification of DNA was conducted using ultraviolet (UV) spectroscopy, and DNA quality was assessed on 0.8% agarose gel. A comparison of genotype frequencies in the different study groups was performed using the Chi-squared test, while a comparison of allelic frequencies was conducted using Fisher's exact test. Results: Variations of alleles, such as 16539423 (G>T), 16539433 (T>G), and 16539629 (A>T) were found only in RA patients. On the other hand, 16539617 (T>A), 16539622 (G>T), and 16539624 (T>C) were found only in control cases. Five sequences (three RA variants and two control variants) with minimal alignment were compared to the wild-type sequence. We found that the sequence modification of pre-miRNA 16539623 del G was significantly higher and had a risk allele in the study group [odds ratio (OR) = 3.29]. Conclusion: Rheumatoid arthritis (RA) is an autoimmune disorder that presents with a variety of clinical manifestations. Genetic factors possibly account for about 60% of disease susceptibility and expression, thus playing a very important role in disease pathogenesis. How to cite this article: Gauri LA, Liyakat N, Dadhich D, et al. Role of miRNA Let-7 in Plasma of Rheumatoid Arthritis. J Assoc Physicians India 2023;71(11):50-52.

A novel missense compound heterozygous variant in TLR1 gene is associated with susceptibility to rheumatoid arthritis - structural perspective and functional annotations.

Besides human leukocyte antigen (HLA-DRB1) locus, more than 100 loci across the genome have been identified and linked with the onset, expression and/or progression of rheumatoid arthritis (RA). However, there are still grey areas in our understanding of the key genetic contributors of the disease, particularly in familial cases. In the present study, we have performed the whole exome sequencing (WES) of RA patients from two consanguineous families of Pakistan in a quest to identify novel, high-impact, RA-susceptibility genetic variants. Through stepwise filtering, around 17,000 variants (common in the affected members) were recognized, out of which 2651 were predicted to be deleterious. Of these, 196 had direct relevance to RA. When selected for homozygous recessive mode of inheritance, two novel pathogenic variants (c.1324T>C, p.Cys442→Arg442; c.2036T>C, p.Ile679→Thr679) in the TLR1 gene displayed the role of compound heterozygosity in modulating the phenotypic expression and penetrance of RA. The structural and functional consequences of the TLR1 missense single nucleotide mutations (Cys442→Arg442; Ile679→Thr679) were evaluated through molecular dynamic simulation (MDS) studies. Analysis showed domain's rigidification, conferring stability to mutant TLR1-TIR/TIRAP-TIR complex with concomitant increase in molecular interactions with pro-inflammatory cytokines, compared to the wild-type conformation. Gene co-expression network analysis highlighted interlinked partnering genes along with interleukin-6 production of TLR1 (corrected p-value 2.98e-4) and acetylcholine receptor activity of CHRNG (corrected p-value 6.12e-2) as highly enriched associated functions. The results, validated through case-control study subjects, suggested that the variants identified through WES and confirmed through Sanger sequencing and MDS are the novel disease variants and are likely to confer RA-susceptibility, independently and/or in a family-specific context. Key Points • Exploration of population based/ethno-specific big data is imperative to identify novel causal variants of RA. • Two new deleterious missense mutations in mutational hotspot exon 4 of TLR1 gene have been identified in Pakistani RA patients. • MD simulation data provides evidence for domain's rigidification, conferring stability to mutant TLR1-TIR/TIRAP-TIR complex, with concomitant increase in production of pro-inflammatory cytokines, thus adding to the onset/erosive outcome of RA.

Long-term use of glucocorticoids in patients with active rheumatoid arthritis: therapeutic "freeze frame"

In Russia, as well as throughout the world, the use of glucocorticoids (GC) in the treatment of rheumatoid arthritis (RA) is widespread, often going beyond the recommendations for both duration and dose regimen, which makes it relevant to study the long-term consequences of such a "wrong" (EULAR, 2022) use of GC in RA therapy. Of 1143 patients with active RA (ACR/EULAR 2010), two groups were formed: A (n=782) RA patients with more than 6 months of experience with systemic GC; group B (n=245) - no experience of taking GC. The cumulative disease index (CIRS) was used to assess the comorbidity profile. Patients in group A were older (p<0.0001), with a longer duration of RA (p=0.0004) and more often with IV radiological stage (p=0.02). With comparable (DAS28) RA activity, the D2T variant of RA was more often detected in them (p=0.036). RA therapy in group A was characterized by a large number of used disease-modifying anti-rheumatic drugs (p=0.0003), more frequent development of methotrexate-induced hepatitis (p=0.03). In group A, the time interval between the onset of RA and the initiation of biological therapy was longer (p=0.0001) and directly correlated with the duration of GC therapy (Rs=0.38) with a comparable qualitative structure of the used b/tsDMARDs. In the same group, tuberculosis, hypertension, chronic kidney disease, cataract and osteoporosis (p<0.05) and its complications were diagnosed significantly more often with a comparable frequency of cardiovascular disease, diabetes, and gastrointestinal lesions. In group A, a higher CIRS multimorbidity index was detected, and the CIRS severity index was lower than in group B (p<0.05). Long-term use of GC did not lead to a decrease in disease activity, inhibition of radiographic progression, delayed the timely administration of b/tsDMARDS and was accompanied by an increase in the multimorbid load.

Identifying shared genetic architecture between rheumatoid arthritis and other conditions: a phenome-wide association study with genetic risk scores.

Rheumatoid arthritis (RA) shares genetic variants with other autoimmune conditions, but existing studies test the association between RA variants with a pre-defined set of phenotypes. The objective of this study was to perform a large-scale, systemic screen to determine phenotypes that share genetic architecture with RA to inform our understanding of shared pathways. In the UK Biobank (UKB), we constructed RA genetic risk scores (GRS) incorporating human leukocyte antigen (HLA) and non-HLA risk alleles. Phenotypes were defined using groupings of International Classification of Diseases (ICD) codes. Patients with an RA code were excluded to mitigate the possibility of associations being driven by the diagnosis or management of RA. We performed a phenome-wide association study, testing the association between the RA GRS with phenotypes using multivariate generalized estimating equations that adjusted for age, sex, and first five principal components. Statistical significance was defined using Bonferroni correction. Results were replicated in an independent cohort and replicated phenotypes were validated using medical record review of patients. We studied n=316,166 subjects from UKB without evidence of RA and screened for association between the RA GRS and n=1317 phenotypes. In the UKB, 20 phenotypes were significantly associated with the RA GRS, of which 13 (65%) were immune mediated conditions including polymyalgia rheumatica, granulomatosis with polyangiitis (GPA), type 1 diabetes, and multiple sclerosis. We further identified a novel association in Celiac disease where the HLA and non-HLA alleles had strong associations in opposite directions. Strikingly, we observed that the non-HLA GRS was exclusively associated with greater risk of the validated conditions, suggesting shared underlying pathways outside the HLA region. This study replicated and identified novel autoimmune phenotypes verified by medical record review that share immune pathways with RA and may inform opportunities for shared treatment targets, as well as risk assessment for conditions with a paucity of genomic data, such as GPA. This research was funded by the US National Institutes of Health (P30AR072577, R21AR078339, R35GM142879, T32AR007530) and the Harold and DuVal Bowen Fund.

Clinical features of ACPA-negative and ACPA-positive variants of rheumatoid arthritis

The aim of the study was to study the features of the clinical picture of the disease in patients with ACPA-negative and ACPA-positive variants of rheumatoid arthritis.Materials and methods. The study included patients with a reliable diagnosis of rheumatoid arthritis (RA) according to the criteria of ACR/EULAR 2010. Depending on the values of the ACPA, two groups of patients were recruited: ACPA-positive and ACPA-negative, comparable in gender, age, duration of the disease and therapy. The nature of the onset and course of the disease, the activity of RA were evaluated (according to the DAS28, SDAI, CDAI indices).Results and discussion. The study included 79 patients with ACPA-negative variant of RA and 79 with ACPA-positive. Age of patients (Me [IR], in years) with the ACPA(–) variant was 52 [39; 62], with the ACPA(+) – 54 [42; 62], the duration of the disease (in months) is 59 [23; 122] and 48 [17; 84] respectively. In ACPA(+) patients, higher disease activity was determined by the indices DAS28-CRP, DAS28-ESR, SDAI, CDAI, values of C-reactive protein and erythrocyte sedimentation rate, a greater number of painful and swollen joints (p&lt;0.05). According to the localization of the involved joints, arthritis of the proximal interphalangeal, metacarpal, wrist and shoulder joints was more often determined in ACPA(+) patients. Systemic manifestations of RA at the time of examination and in the anamnesis were statistically significantly more common in ACPA(+) (32.9%) than in ACPA(–) (17.7%). Of the systemic manifestations, rheumatoid nodules were more common in ACPA(+) patients, a tendency to a higher frequency of neuropathy, scleritis and episcleritis was revealed in ACPA(–) patients.Conclusion. In patients with ACPA(–) subtype, clinical signs of joint damage and the inflammatory component are less pronounced compared to ACPA(+). However, the mixed picture of manifestation, the less “bright” course of the disease, the absence of characteristic immunological biomarkers necessitate long-term and careful monitoring of this group of patients. At the same time, the subjective severity of the disease and dysfunction due to ankylosing joints do not differ from the ACPA(+) variant of RA.

ACCP-negative rheumatoid arthritis – clinical and immunological features

Depending on the presence of laboratory biomarkers: rheumatoid factor IgM and anti-cyclic citrullinated peptide antibodies (ACCP), “seropositive” and “seronegative” variants of rheumatoid arthritis (RA) are distinguished. Immunological subtypes differ in risk factors, immunopathogenesis, and the course of the disease. A review of data concerning immunology and clinical features of ACCP-negative rheumatoid arthritis is presented. The presence of ACCP in the peripheral blood reflects the progressive erosive process with a predominance of the inflammatory component and involvement of the B cells. Proliferative changes predominate in the ACCPnegative subtype; disorders associated with the T-cell link, primarily with CD4+ T-lymphocytes, play an important role in pathogenesis. This variant of the disease is characterized by a less pronounced erosive process, but the inflammatory activity in both subtypes of RA can be comparable. Early diagnosis, regular monitoring of the disease activity and the «treat to target» strategy are recommended for both positive and negative ACCP RA, however, the effectiveness of individual drugs in these subtypes may vary significantly.

SLAMF6 is associated with the susceptibility and severity of rheumatoid arthritis in the Chinese population

ObjectivesA recently published genome-wide association study identified six novel loci associated with rheumatoid arthritis (RA) in Korean population. We aimed to investigate whether these newly reported RA-risk loci are associated with RA in the Chinese population and to further characterize the functional role of the susceptible gene.MethodsThe susceptible variants of RA were genotyped in 600 RA patients and 800 healthy controls, including rs148363003 of SLAMF6, rs117605225 of CXCL13, rs360136 of SWAP70, rs111597524 of NFKBIA, rs194757 of ZFP36L1 and rs1547233 of LINC00158. Synovial tissues were collected from the knee joint of 50 RA patients and 40 controls without osteoarthritis for the gene expression analysis. Inter-group comparisons were performed with the Chi-square test for genotyping data or with Student's t-test for gene expression analysis.ResultFor rs148363003 of SLAMF6, RA patients were observed to have a significantly lower frequency of genotype CC (4.5% vs. 0.9%, p = 0.004) as compared with the controls. The frequency of allele C was remarkably higher in the patients than in the controls (11.5% vs. 8.0%, p = 0.002), with an odds ratio of 1.49 (95% CI = 1.16–1.92). There was no significant difference between the patients and the controls regarding genotype or allele frequency of the other 5 variants. The mRNA expression of SLAMF6 was 1.6 folds higher in the RA patients than in the controls. Moreover, SLAMF6 expression was 1.5 folds higher in patients with genotype CC than in the patients with genotype TT.ConclusionsSLAMF6 was associated with both the susceptibility and severity of RA in the Chinese population. Moreover, rs148363003 could be a functional variant regulating the tissue expression of SLAMF6 in RA patients. It is advisable to conduct further functional analysis for a comprehensive knowledge on the contribution of this variant to the development of RA.

ASSOCIATION OF SEROLOGICAL STATUS WITH THE FREQUENCY OF CLINICAL AND RADIOLOGICAL REMISSION IN RHEUMATOID ARTHRITIS

Relevance. Achieving remission is one of the main goals in the treatment of patients with rheumatoid arthritis (RA). One of the determining predictors of the disease, according to the literature, is the serological variant of RA. However, there are conflicting data in scientific publications on the relationship between the presence of antibodies to cyclic citrullinated peptide (ACCP) and / or rheumatoid factor (RF) and the frequency and rate of remission. There is no unanimous opinion in the literature on the influence of the titer of serological markers of RA (ACCP and RF) on the possibility of achieving remission on the background of basic treatment, which prompted to conduct their own research to study this issue. Objective: to study the relationship between the presence / absence of serological markers of RA (ACCP, RF) and the frequency and timing of clinical and radiological remission of RA under the influence of treatment with traditional synthetic basic drugs and to analyze the relationship between ACCP and RF titers and the possibility of remission.Material and methods. The study analyzed the influence of serological status of patients with RA on the possibility and time of remission while taking the main non-biological basic drugs. The relationship between the presence and level of ACCP and / or RF and clinical and radiological remission in RA has been studied. The study included 128 patients. Analysis of RA activity and assessment of remission were performed after 6, 12 and 24 months of treatment, using the DAS28 activity scale and the dynamics of radiological changes on the Sharpe-van der Heide scale. Results. During the 2-year follow-up, clinical remission was observed three times more often in the group of patients negative for ACCP (anti-cyclic citrullinated peptide) (36.1% in the group ACCP-RF- compared with 12.5% ​​in the group ACCP + RF ( +, χ2 = 7.74, p &lt; 0.05, and in 33.3% in the group ACCP-RF +, a significant difference compared with ACCP + RF +, χ2 = 4.55, p &lt;0.05). Early remission (during the first 6 months of treatment) was also more common in the group of patients with no ACCP (χ2 = 10.7, p &lt;0.01 and χ2 = 6.69, p &lt;0.05, respectively). The rate of remission (the share of early in the structure of the total) in the four analyzed groups did not differ significantly and was 75%, 66.6%, 66.6% and 84.6%, respectively. The titer of ACCP in the group of patients who achieved remission was 240.8 ± 38.5 and did not differ significantly from that in the group of patients whose RA (rheumatoid arthritis) activity exceeded the remission threshold (187.8 ± 13.7, p&gt; 0.05). There was also no significant difference between these two groups in the titers of the RF (rheumatoid factor): 257.9 ± 233.8 and 293.2 ± 257.3, respectively. Radiological remission was achieved in 46.7% of ACCP-negative patients and only in 10.6% of ACCP-positive patients (p &lt;0.01). The absence of RF in the blood was also associated with a more frequent achievement of radiological remission (in 34.2% of patients) compared with the RF-positive cohort of patients (in 15.4%, p &lt;0.05). Conclusions. It was found that the frequency of clinical remission, including early (during the first 6 months of treatment), is three times higher in patients with RA, negative for ACCP. The rate of clinical remission (ratio of early in the structure of the general) does not depend on the serological variant of the disease: about two thirds of patients in all analyzed groups achieve remission in the first half of basic therapy. Titers of the main serological markers of RA (ACCP and RF) in the onset of the disease do not affect the possibility of achieving clinical and radiological remission. Radiological remission is observed three times more often in seronegative (for ACCP or RF) patients. Double seropositivity has an additive effect on subsequent joint destruction.

Influence of the FCGR2A rs1801274 and FCGR3A rs396991 Polymorphisms on Response to Abatacept in Patients with Rheumatoid Arthritis.

Abatacept (ABA) is an immunosuppressant indicated for treatment of rheumatoid arthritis (RA). Effectiveness might be influenced by clinical RA variants and single-nucleotide polymorphisms (SNPs) in genes encoding protein FCGR2A (His131Arg) and FCGR3A (Phe158Val) involved in pharmacokinetics of ABA. An observational cohort study was conducted in 120 RA Caucasian patients treated with ABA for 6 and 12 months. Patients with the FCGR2A rs1801274-AA genotype (FCGR2A-p.131His) showed a better EULAR response (OR = 2.43; 95% CI = 1.01–5.92) at 12 months and low disease activity (LDA) at 6 months (OR = 3.16; 95% CI = 1.19–8.66) and 12 months (OR = 6.62; 95% CI = 1.25–46.89) of treatment with ABA. A tendency was observed towards an association between the FCGR3A rs396991-A allele (FCGR3A-p.158Phe) and better therapeutic response to ABA after 12 months of treatment (p = 0.078). Moreover, we found a significant association between the low-affinity FCGR2A/FCGR3A haplotypes variable and LDA after 12 months of ABA treatment (OR = 1.59; 95% CI = 1.01–2.58). The clinical variables associated with better response to ABA were lower age at starting ABA (OR = 1.06; 95% CI = 1.02–1.11) and greater duration of ABA treatment (OR = 1.02; 95% CI = 1.01–1.04), lower duration of previous biological therapies (OR = 0.99; 95% CI = 0.98–0.99), non-administration of concomitant disease-modifying antirheumatic drugs (DMARDs) (OR = 24.53; 95% CI = 3.46–523.80), non-use of concomitant glucocorticoids (OR = 0.12; 95% CI = 0.02–0.47), monotherapy (OR = 19.22; 95% CI = 2.05–343.00), lower initial patient’s visual analogue scale (PVAS) value (OR = 0.95; 95% CI = 0.92–0.97), and lower baseline ESR (OR = 0.92; 95% CI = 0.87–0.97). This study showed that high-affinity FCGR2A-p.131His variant, low-affinity FCGR3A-p.158Phe variant, and combined use of FCGR2A/FCGR3A genetic variations could affect ABA effectiveness. Further studies will be required to confirm these results.

Genetic variants shape rheumatoid arthritis-specific transcriptomic features in CD4+ T cells through differential DNA methylation, explaining a substantial proportion of heritability

ObjectiveCD4+ T cells have been suggested as the most disease-relevant cell type in rheumatoid arthritis (RA) in which RA-risk non-coding variants exhibit allele-specific effects on regulation of RA-driving genes. This...

Large-scale meta-analysis across East Asian and European populations updated genetic architecture and variant-driven biology of rheumatoid arthritis, identifying 11 novel susceptibility loci

ObjectivesNearly 110 susceptibility loci for rheumatoid arthritis (RA) with modest effect sizes have been identified by population-based genetic association studies, suggesting a large number of undiscovered variants behind a highly...

Spondyloarthritis evolution: what is in your history?

This review encompasses a detailed history of spondyloarthritis (SpA) evolution as early as the 17th century, continues on to the current concept of SpA, and ends with current gaps in our understandings of SpA. Until the early 1960s, ankylosing spondylitis and other SpA family members were considered to be variants of rheumatoid arthritis (RA). The formal medical community separated them from RA at that time, and shortly thereafter they were recognized to be inter-connected based on shared clinical, laboratory, and imaging features. The last two decades have witnessed the formal distinction between axial and peripheral SpA and the connections that exist between nonradiographic and radiographic axial SpA. Recent studies have revealed different microbial compositions among patients with SpA and healthy controls and also between HLA-B27 positive and negative healthy individuals. Further investigation of the roles of intestinal microbiome and physical force transduction toward SpA pathogenesis, strategies to improve delay in SpA diagnosis, biomarkers to better predict radiographic progression, and modification of current classification criteria to better address the axial and peripheral groups are gaps in our understandings that pose top priorities for SpA research.

Severely destructive unilateral wrist arthritis as a rare variant of rheumatoid arthritis: analysis of clinical and imaging features

Rheumatoid arthritis (RA) is a common autoimmune disease typically affecting joints symmetrically. A small number of patients develop unilateral and severely destructive wrist arthritis (DWA). The objective of our study was to characterise patients with this type of affection. This was a retrospective cohort study of RA patients with positive RF/anti-CCP antibodies. Clinical characteristics, including, age, gender, disease duration, dexterity, occupational history, smoking status, and the number of prescribed DMARDs were recorded. Conventional radiographs were evaluated using the modified Sharp/van der Heijde scoring (mSS) method. We analysed our laboratory database of 1247 patients and identified 559 patients with a clinical diagnosis of RA. For 395 of the patients, radiographs of the hands were available for evaluation. 25 patients had extensive unilateral DWA, corresponding to a prevalence of 6.3% (25 of 395 patients). 11 patients were excluded due to incomplete data. Of the remaining 14 patients, 13 were female with a median age of 61 (33-83) years, and median disease duration of 18 (1-33) years. 8 of 11 (72.7%) patients were smokers; in three, smoking status was not known. 80% with known dexterity developed unilateral DWA in the dominant hand. Total mSS was significantly higher on the affected side (39, interquartile range 35.25-46.25) versus non-affected (13, IQR 3-23). MSS were not different if the carpal bones were excluded from scoring. Side of involvement (left vs. right), or dominant versus non-dominant hand, did not result in a different mSS. Unilateral DWA is a rare variant of RA which predominantly affects women who smoke.

Subclinical features of atherosclerotic remodeling of arteries in patients with rheumatoid arthritis

The aim of the research – to study the structural-functional state of artery walls in patients with rheumatoid arthritis depending of disease duration, seropositivity for rheumatoid factor/ cyclic citrullinated peptide antibodies, disease activity. Materials and methods. 82 patients with rheumatoid arthritis were investigated: 19 men (23.1 %) and 63 women (76.9 %), the average age of whom was (37.6 ± 5.1) years old. The control group consisted of 30 apparently healthy persons. In all the patients measurements of diameter and thickness of intima-media complex of common carotid arteries were carried out, the stiffness index was calculated. Results. 47.5 % (n = 39) of patients had rheumatoid arthritis with the present illness duration less than 3 years, in 47.5 % of patients (n = 39) the duration of rheumatoid arthritis was more than 3 years. In 48 (58.5 %) of patients rheumatoid factor/cyclic citrullinated peptide antibodies were present – seropositive variant of rheumatoid arthritis, in 34 (41.5 %) patients – rheumatoid factor/cyclic citrullinated peptide antibodies seronegative variant of the disease. Within all investigated patients with rheumatoid arthritis the highest rates of intima-media thickness complex of common carotid arteries were detected in patients with longer-term (more than 3 years) present illness rheumatoid factor/cyclic citrullinated peptide antibodies of seropositive rheumatoid arthritis; in patients of this group higher stiffness index of common carotid arteries was also detected that characterizes the local (carotid) rigidity of artery wall. Correlation analysis showed the existence of direct relationship between DAS28 and intima-media complex of common carotid arteries, the duration of rheumatoid arthritis and stiffness index of intima-media complex of common carotid arteries, and also between their size and the level of rheumatoid factor, cyclic citrullinated peptide antibodies, which shows the substantial contribution of activity and duration of autoimmune inflammation course in rheumatoid arthritis to changes of common carotid arteries architectonics. Conclusions. The data obtained demonstrate the existence of subclinical lesion of common carotid arteries in patients with rheumatoid arthritis and absence of cardiovascular diseases, more significant in long-term course (more than 3 years) of seropositive for rheumatoid factor/ cyclic citrullinated peptide antibodies disease variant.

Changes the cytokine profile and calcium-regulating hormones in rheumatoid arthritis.

The aim was to study the level of some cytokines (İL-2, İL-6, İL-8 TNFα) and calcium regulating hormones (calcitonin, parathyroid hormone, 25 (OH) D) in the blood of patients with rheumatoid arthritis (RA) depending on rheumatoid factor (RF) and the assessment of the role of the revealed violations in the pathogenesis of bone loss in this pathology. For this purpose, 74 patients with RA (59 women, 15 men) aged from 27 to 71 were examined. On the basis of RF in the blood serum, the patients were divided into 2 groups: seronegative and seropositive RA. The control group included 16 healthy individuals (13 women, 3 men). The results obtained that the serological variant of RA affects the serum levels of proinflammatory cytokines and calcium-regulating hormones: more pronounced changes were found in seropositive RA. The high production of IL-2, IL-6, IL-8, TNF-α and parathyroid hormone detected in both groups of patients undoubtedly contributes to the mechanisms of bone loss in RA. In both groups we detected hypovitaminosis D. This results recommended to use this vitamin in the complex treatment of RA.

CHANGES THE CYTOKINE PROFILE AND CALCIUM-REGULATING HORMONES IN RHEUMATOID ARTHRITIS

The aim was to study the level of some cytokines (İL-2, İL-6, İL-8 TNFα) and calcium regulating hormones (calcitonin, parathyroid hormone, 25 (OH) D) in the blood of patients with rheumatoid arthritis (RA) depending on rheumatoid factor (RF) and the assessment of the role of the revealed violations in the pathogenesis of bone loss in this pathology. For this purpose, 74 patients with RA (59 women, 15 men) aged from 27 to 71 were examined. On the basis of RF in the blood serum, the patients were divided into 2 groups: seronegative and seropositive RA. The control group included 16 healthy individuals (13 women, 3 men). The results obtained that the serological variant of RA affects the serum levels of proinflammatory cytokines and calcium-regulating hormones: more pronounced changes were found in seropositive RA. The high production of IL-2, IL-6, IL-8, TNF-α and parathyroid hormone detected in both groups of patients undoubtedly contributes to the mechanisms of bone loss in RA. In both groups we detected hypovitaminosis D. This results recommended to use this vitamin in the complex treatment of RA.

Palindromic rheumatism as part of the rheumatoid arthritis continuum.

Palindromic rheumatism is a distinctive syndrome that has a long-recognized association with rheumatoid arthritis (RA). Palindromic rheumatism is characterized by intermittent flares of pain, erythema and swelling in and around the joints, which are typically severe and unpredictable. The observation that most patients with palindromic rheumatism haveRA-related autoantibodies and that many eventually develop RA has led to palindromic rheumatism often being viewed as a relapsing-remitting variant of RA. However, the clinical andimaging phenotypes of palindromic rheumatism suggest important distinctions from RA and imply underlying mechanistic differences between the two conditions. Furthermore, the pattern of inflammation seen in palindromic rheumatism has interesting parallels with that seen in other groups of symptomatic individuals at risk of developing RA. In this Review, we explore the concept of palindromic rheumatism as part of the RA continuum and propose an updated disease paradigm for this unique syndrome.

Influence of immunological markers of cardiovascular risk on atherosclerosis early development in patients with rheumatoid arthritis

Aim of the study. To investigate the peculiarities of immunological markers of systemic inflammation in patients with rheumatoid arthritis (RA) depending on the clinical-immunological variant of the course of RA and on the duration of the disease.Materials and methods. We examined 82 patients with RA, aged (37.6±5,1) years. The history of the disease was less than 3 years in 47.5 % of patients (n=39) and in 52.5 % of patients (n=43) – it was more than 3 years. In 48 (58.5 %) patients a seropositive variant of RA was observed and 34 (41.5 %) patients were with seronegative variant of the disease. All patients underwent a complex clinical, laboratory and immunological examination. RA activity was assessed using the DAS 28 index; immune-enzyme assay method was used to assess the level of rheumatoid factor (RF), antibodies to cyclic citrulinated peptide (ACCP), C-reactive protein (CRP), proinflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6).Results. The levels of pro-inflammatory cytokines in RA showed a statistically significant increase in their concentration in all groups of examined patients compared with the control one. The highest levels of TNF-α (p=0.046) and IL-1β (p=0.025) were in the group of patients with the seronegative variant of RA lasting less than 3 years; the highest concentration of IL-6 (p=0.018) was determined in patients with a long course of seropositive RA. Correlation analysis allowed determining the association of hyperproduction of TNF-α, IL-1β and IL-6 with the duration of RA and disease activity. In all groups of patients with RA an increase in the serum CRP concentration was detected. It was more expressed in patients with a seropositive variant of RA with a disease duration of more than 3 years. In addition, correlation links between CRP and IL-6, IL-1β, TNF-α have been established. The direct correlation between the level of CRP and the DAS28 index (p&lt;0.0001), RF concentration, ACCP (p=0.05) was also revealed.Conclusions. A study in the serum of mediators of immune inflammation in patients with different clinical and immunological variants and duration of RA revealed differences in their content. In patients with anamnesis of RA less than 3 years, a predominant increase in TNF-α and IL-1β was detected in case of a seronegative disease type. In patients with a disease duration of seropositive RA for more than 3 years, the content of IL-6 was increased largely, compared with rates in patients with a similar duration of the seronegative disease. In patients with a RA seropositive duration of more than 3 years, the CRP content was 1.3 times (p=0.05) higher than in the group of patients with a history of the disease less than 3 years and 1,6 times (p=0.001) higher than in patients with similar duration of seronegative RA