Cyclic Citrullinated Peptide Antibodies Research Articles

Study of the Association between MTHFR Polymorphism (rs1801133) and the Outcome of Methotrexate Treatment in Rheumatoid Arthritis Patient

Abstract Background Rheumatoid arthritis is a chronic systemic autoimmune disease that causes loss of joint function and significantly reduces the quality of life. Methotrexate is one of the disease- modifying anti-rheumatic drugs that can influence treatment efficacy and toxicity. Methotrexate is used as an anchor drug for the treatment of rheumatoid arthritis and there may be differences in drug action between genotypes. Aim of the Work The present study was aimed to evaluate the impact of methylenetetrahydrofolate reductase (MTHFR) gene C677T (rs1801133) polymorphism on the clinical outcome of methotrexate treatment as regards treatment efficacy or toxicity in Egyptian rheumatoid arthritis patients. Subjects and Methods This study conducted on 45 patients diagnosed with rheumatoid arthritis receiving methotrexate as a first line of treatment. Subjects were classified into two groups; group I (responders, n = 25) and group II (non-Responders, n = 20) according to clinical response to methotrexate by using disease activity score (DAS28). Complete blood count, erythrocyte sedimentation rate, liver function, renal function, C- reactive protein, cyclic citrullinated peptide antibody and rheumatoid factor were done for all patients. Determination of methylenetetrahydrofolate reductase gene C677T (rs1801133) polymorphism was carried out using Real-time polymerase chain reaction. Results The present study did not confirm the presence of a significant association between the genotypic frequencies of the methylenetetrahydrofolate reductase gene C677T (rs1801133) polymorphism among the responders and the non-responders group in patients with rheumatoid arthritis. In addition, the methylenetetrahydrofolate reductase gene C677T (rs1801133) polymorphism did not show significant difference between disease complications among the responders and the non-responders groups. On the other hand, our findings suggested that a statistically significant difference was found between two groups of patients regarding disease activity score (DAS 28). Conclusion The current study revealed that there is no significant association between the genotypic frequencies of the methylenetetrahydrofolate reductase gene C677T (rs1801133) polymorphism among the responders and the non-responders groups of patients with rheumatoid arthritis. Moreover, the methylenetetrahydrofolate reductase gene C677T (rs1801133) polymorphism did not show significant difference between disease complications among the responders and the non-responders groups in patients with rheumatoid arthritis.

Estimation of interleukin-6 level and atherogenic indices as predictors of severity of rheumatoid arthritis in Iraqi patients

Background & Objective: Rheumatoid Arthritis (RA) is an inflammatory illness that causes joint degeneration and inflammation of the synovial membrane, leading to significant disability over time. Interleukin-6 (IL-6) is a widely distributed pro-inflammatory cytokine that has a variety of roles in several pathophysiologic systems, most notably in the RA development. The purpose of this study was to assess the blood levels of IL-6 and the severity and activity of RA in patients, and to assess the association of atherogenic indices with IL-6 as a predictor of severity in RA disease. Methodology: This study was a case control observational study involving 300 participants diagnosed with RA by the rheumatologists in accordance with American College of Rheumatologists (ACR)/ European League Against Rheumatism (EULAR) 2010 criteria. Serum levels of IL-6, CRP, RF and ACPA were measured by using ELISA technique. While, lipid profile was determined with spectrophotometry. Receiver operating curve (ROC) was used to study the opportunity of using atherogenic indices and IL-6 as diagnostic tools for RA. Results: The results indicated a higher IL-6 level in RA patients in comparison to the control group, e.g., 28.55 (18.76-41.07) pg/mLvs 10.19 (6.11-12.50) pg/ml. High atherogenic index of plasma (AIP) risk > 0.24 in RA patients parameters (GDF-15, IL-6), the lipid profile parameters and atherogenic indices (TC, TG, VLDL-C, LDL-C, CRI-I, CRI-II, AIP, and AC) were compared with moderate atherogenic risk (AIP < 0.24) in RA patients. While a significant decrease was recorded in the HDL-C and BMI levels, it had significantly high atherogenic risk (AIP > 0.24) compared with moderate atherogenic risk (AIP < 0.24) in RA patients. The ROC results analysis showed that the top 5 highly sensitive predictors for RA, e.g., CRI-I, AC, AIP, CRI-II followed by IL-6, have a relatively good sensitivity and specificities for predictors for RA. Conclusion: Increase in interleukin-6 may indicate the activity and severity of the disease. This biomarker could be helpful for early disease detection. The results showed a higher IL-6 in RA patients as well as increased dyslipidemia and atherogenicity in RA patients. Elevation of serum IL-6 and atherogenic indices are the best predictors for RA patients with a higher risk of atherosclerosis than other biomarkers. There is an important correlation between atherogenic indices parameters and the immunological biomarkers IL-6 indicating a significant role of the inflammation in the incidence of atherogenic indices in RA. Abbreviations: AUC- Area Under Curve; ACPA - Anti Cyclic Citrullinated Peptide Antibodies; CRP- C-Reactive Protein; ESR- Erythrocyte Sedimentation Rate; RF- Rheumatoid Factor; BMI- Body Mass Index; GDF-15 -Growth Differentiation Factor-15; DAS28-CRP- Disease Activity Score-28-C-Reactive Protein; TC- Total Cholesterol; TG- Triglyceride; HDL-C -High Density Lipoprotein Cholesterol; LDL-C -Low Density Lipoprotein Cholesterol; VLDL-C-Very Low Density Lipoprotein Cholesterol; AC-Atherogenic Coefficient; AIP-Atherogenic Index of Plasma; CR-I, CR-II- Castelli’s Risk Indexes. Keywords: Rheumatoid Arthritis, Interleukin-6, Atherogenic Indices. Citation: Abdulridha GAO, Hussein MA, Majeed SR. Estimation of interleukin-6 level and atherogenic indices as predictors of severity of rheumatoid arthritis in Iraqi patients. Anaesth. pain intensive care 2024;28(4):700−705; DOI: 10.35975/apic.v28i4.2400. Received: February 26, 2024; Reviewed: April 16, 2024; Accepted: July 09, 2024

Time to start disease modifying drugs for adults with seropositive rheumatoid arthritis: results of the first year of the national New Zealand Rheumatology Association (NZRA) audit.

This audit describes variation in the time from referral to starting disease modifying drug (DMARD) for people with newly diagnosed seropositive rheumatoid arthritis (RA), how frequently this was within the recommended 6 weeks and whether regional, service-level or patient-level factors were associated with this variation. Rheumatologists submitted data on new patients with a new diagnosis of rheumatoid factor and/or cyclic-citrullinated peptide antibody positive RA. The association between visit funding, ethnicity, socio-economic deprivation, rurality, local specialist staffing levels and the time to DMARD treatment was assessed using Cox proportional-hazard models. Data were collected on 355 patients over 12 months. Overall, 64.8% of patients commenced DMARD treatment within 6 weeks of referral and this was associated with rheumatologist FTE per 100,000 population (adjusted HR 2.47, 95%CI 1.27-4.81; p=0.008) and the rurality (Geographic Classification of Health [GCH]) of the patient (for R2 compared to U1 adjusted HR 0.20, 95%CI 0.09-0.43; p<0.001). There was no association between time to DMARD and ethnicity or socio-economic deprivation. There was significant variation in time to DMARD treatment, mainly related to variation in rheumatologist staffing levels and patient rurality. Rheumatologist staffing levels of 1.0 FTE/100,000 population was associated with 80% of patients meeting the recommended 6-week time to DMARD treatment.

Bone mineral density in women with rheumatoid arthritis: A link between immune and biochemical markers

To study the association of bone mineral density (BMD) with serum biochemical and immunological markers in postmenopausal women with rheumatoid arthritis (RA). The study included 173 women with RA (age 61.0 [56.0; 66.0] years). A survey, dual-energy X-ray absorptiometry to measure the BMD of the lumbar spine (LI-LIV), femoral neck (FN) and total hip (TH), routine blood chemistry, measurement of C-reactive protein (CRP), rheumatoid factor, cyclic citrullinated peptide antibodies (CCPA), parathyroid hormone (PTH), vitamin D3, myostatin, follistatin, interleukin-6 (IL-6), IL-6 receptors, insulin-like growth factor 1, adiponectin, leptin, fibroblast growth factor 23, and tumor necrosis factor SF12 were performed. PTH (β=-0.22, -0.35 and -0.30 for LI-LIV, FN and TH, respectively), CRP (β=-0.18, 0.23 and -0.22 for LI-LIV, FN and TH, respectively) and leptin (β=0.35, 0.32 and 0.42 for LI-LIV, FN and TH, respectively) were shown a significant association with BMD in all sites of measurement. It was independent of age, body mass index and postmenopause duration. Associations were also found between adiponectin and BMD of LI-LIV and TH (β=-0.36 and -0.28, respectively), CCPA and BMD of FN and TH (β=-0.21, -0.24, respectively) and IL-6 and BMD of FN (β=0.37). The study of biochemical and immunological markers in women with RA demonstrated that CRP, CCPA, PTH, IL-6, adiponectin, and leptin influenced BMD.

Identification of citrullinated α1-antitrypsin (A1AT) in saliva in a mouse model of rheumatoid arthritis

ObjectivesRheumatoid arthritis (RA) is an autoimmune disease characterized by progressive joint destruction. Early diagnosis and treatment, before joint deformation or destruction occurs, are crucial. Identifying novel biomarkers for RA in saliva could potentially enable early detection of the disease, prior to its onset. MethodsWe conducted a comprehensive proteomic analysis of salivary proteins in a mouse model of RA. Proteins were identified using western blotting and enzyme-linked immunosorbent assay in the serum, saliva, and ankle joints of DBA/1JJmsSlc mice, a model of RA. Ankle joints and submandibular glands were stained with hematoxylin and eosin and immunostained, and the results were compared with those of control mice. ResultsCitrullinated alpha-1 antitrypsin (A1AT, 46 kDa) was commonly detected in the saliva, serum, and ankle joints of mice with severe RA and was confirmed through proteomic analysis. Western blotting showed a band corresponding to 46 kDa in the serum, saliva, and ankle joints. Immunostaining of the ankle joints with the A1AT antibody showed a strong positive signal in the synovium. ConclusionsIn DBA/1JJmsSlc mice, cyclic citrullinated peptide antibodies and A1AT may be involved in citrullination and contribute to the development and severity of RA, making them valuable treatment targets requiring further study.

Prediction of Cardiovascular Diseases in Women With Rheumatoid Arthritis.

To develop prognostic models for arterial hypertension (AH) and atherosclerosis based on studying the totality and significance of traditional and disease-mediated risk factors (RFs) in women with rheumatoid arthritis (RA). 223 female patients with RA aged 54.9±2.1 years were evaluated at the premises of the polyclinic of the Gulla Municipal Hospital #4 (Barnaul), the "Health Center", the City Rheumatology Department of the polyclinic, and the Hospital Department in 2016-2019. Statistical analysis was performed using Excel Microsoft Office 2007, Statistica 6.0 and 10.0, and SigmaPlot 12.5 software packages. Multivariate regression analysis was used for studying the attributes influencing the development of AH and atherosclerosis in RA and for constructing predictive models. ROC analysis was used to determine the quality of the developed models. Differences were considered statistically significant at p&lt;0.05. The following RFs predominating in the onset of disease were identified: traditional (hyperglycemia, obesity, increased diastolic BP (DBP), tachycardia, dyslipidemia); disease-mediated (ESR, fibrinogen, C-reactive protein (CRP), rheumatoid factor, cyclic citrullinated peptide antibodies, moderate and high DAS-28 activity), and psychosocial (stress, anxiety, depression, sleep disorders). The highest RF incidence and their combinations were determined with a RA duration of more than a year: traditional (obesity, hyperglycemia, increased systolic BP (SBP)), and decreased glomerular filtration rate; and disease-mediated (prednisolone treatment). A highly sensitive model for AH screening was developed that included a combination of RFs: disease-mediated (RA duration, CRP); traditional (improper diet, low physical activity, history of early cardiovascular diseases, increased SBP and DBP, preeclampsia and/or eclampsia, early menopause, older age, dyslipidemia); psychosocial (anxiety, depression), and a high salt-taste threshold. A highly sensitive model was developed for probable prediction of multifocal atherosclerosis in RA in women. The model includes a complex of risk factors: disease-mediated (RA activity by DAS-28, CRP, fibrinogen, ESR, dose-dependent prednisolone treatment); traditional (AH, SBP, waist circumference, heart rate, early menopause, preeclampsia and/or eclampsia, age 55 years and older, dyslipidemia); and psychosocial (sleep disorders, depression). Algorithms for early prevention of AH and atherosclerosis were developed with consideration of identified predictors and proposed prediction models for women with RA.

Plasma TNF-α Elevation in Biologic Naive Rheumatoid Arthritis Patients Belonging to a Population with New Mutations in TLR4 and CYP51A1 genes without Association with Disease-Related Antibodies Levels.

In a system biology-based study, we previously reported that IL-6 and IL6R -specific m-RNA levels were elevated in leukocytes of patients with Rheumatoid arthritis (RA). Here, the association of toll-like receptor4 (TLR4) rs 141534085 and cytochrome P450 family 51 subfamily A member 1(CYP51A1) rs6 with tumor necrosis factor-α (TNF- α), rheumatoid factor (RF)- and Anti- cyclic citrullinated peptide (anti-CCP) antibody -positivity was investigated in almost the same subjects. Forty-six patients and 48 normal subjects were recruited in this study. The blood leucocytes TLR4 rs 141534085 and CYP51A1 rs6 -comprising DNA sequences were amplified by using tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) technique and the PCR products were checked by Sanger DNA sequencing method. ELISA method was used to determine plasma levels of TNF- α, anti-CCP antibody and RF positivity of plasma was evaluated through a latex agglutination test. The TNF- α level was significantly higher in the patient group than control subjects (p= 0.001). Moreover, we were not able to find any correlation between TNF-α levels and RF as well as anti-CCP antibodies when we used the K2/ Fisher's exact test and Pearson test respectively. Our DNA sequencing data revealed the following new mutations in TLR4 rs141534085 comprising regions: A>T in position 1050, T>A in position 1052, and C>A in position 1054; and for CYP51A1 rs6 encompassing region, the new mutations were; G>A in position 21680, the T nucleotide was inserted in position 21762 and the G nucleotide was inserted in position 21763, G>T in position 21764. The data of this study showed that both TLR4 rs141534085 and CYP51A1 rs6 related DNA regions should be considered as hotspot areas in RA pathogenicity. Moreover, these data indicated that, TNF- α did not alter the production of anti-CCP and RF pathogenic antibodies in patients with long-term RA.

A study of the roles of some immunological biomarkers in the diagnosis of rheumatoid arthritis.

Autoimmune rheumatoid arthritis (RA) is a systemic condition closely correlated with a variety of autoantibodies (Abs) that could be considered diagnostic and prognostic markers. The current research was designed to detect the diagnostic values for a number (n) of these auto-Abs in RA detection and to evaluate the accuracy of a combined diagnostic scheme. This prospective study was conducted between September 2021 and August 2022 and included 110 subjects with RA, 70 individuals with other autoimmune disorders as positive controls (PC), and 50 unrelated, apparently healthy individuals as healthy controls (HC). The eligibility criteria for all study groups were followed stringently. An enzyme-linked immunosorbent assay (ELISA) was employed to measure rheumatoid factors (RF), cyclic citrullinated peptide antibodies (CCP-Abs), mutated citrullinated vimentin antibodies (MCV-Abs), anti-perinuclear factor antibodies (APF-Abs), and anti-keratin antibodies (AKA). We calculated the specificity, sensitivity, and predictive values of all auto-Abs. Significantly higher levels of anti-CCP-Abs, anti-MCV-Abs, APF-Abs, and AKAs were reported in the RA patients compared to the HC and PC subjects. RF levels, however, were only statistically elevated when compared to the HC individuals. Anti-APF-Abs had a higher sensitivity rate (70.9%), and anti-CCP-Abs had a higher specificity rate (94.16%) compared to other auto-Abs, whereas the combined detection scheme revealed a higher sensitivity (81.81%) and excellent specificity (90.83%) compared to the two former auto-Abs. Anti-perinuclear factor-Ab was a highly sensitive test, and CCP-Ab was a surpassingly specific assay for identifying RA. Furthermore, the combined detection scheme is an essential serological approach for RA diagnosis and crucial in differentiating this disease from other autoimmune diseases, thus promoting early diagnosis and treatment.

Evaluation of Serum Ghrelin and Leptin Levels in Patients with Celiac Disease, Type1Diabetes Mellitus and Rheumatoid Arthritis

Ghrelin and leptin are two hormones that possess multiple functions, including appetite regulation, maintenance of the tissue homeostasis and regulation of proinflammatory cytokines. A few studies on serum ghrelin and leptin levels in autoimmune diseases have exhibited conflicting results. Therefore, the present study aimed to investigate the relationship between the two energy balance hormones and autoimmune diseases. Serum ghrelin and leptin levels were assessed in 94 adult patients, 61 females and 33 males, with various autoimmune diseases (celiac disease, type 1 diabetes mellitus and rheumatoid arthritis) as well as in 35 healthy people as controls, using commercially available ELISA kits. Statistically important distinctions (P &lt; 0.05) were found between the patients and controls with regard to serum ghrelin and leptin levels. Moreover, females had higher mean serum ghrelin and leptin levels than males. On the other hand, serum ghrelin level was positively correlated with serum leptin levels (r = 0.399, P &lt; 0.05) in the RA group. Whereas no significant correlation (P &gt; 0.05) was found between serum ghrelin and leptin levels in both CD and T1DM groups. As well as the correlation of the diseases biomarkers (tissue transglutaminase antibodies, anti-tTG; glutamic acid decarboxylase antibodies, anti-GAD; and cyclic citrullinated peptide antibodies, anti-CCP) with ghrelin/leptin levels revealed that anti-CCP was the only marker that significantly (P &lt; 0.05) associated with ghrelin and leptin in patients with RA. The current study indicates a linkage between the immune system and metabolic hormones depending on response to different autoimmune conditions. Additional studies are required to understand whether changes in ghrelin-leptin levels influence the emergence of autoimmune diseases or vice versa.

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.

Rapid Production of Cyclic Citrullinated Peptide Monoclonal Antibody in Nicotiana benthamiana for the Early Detection and Diagnosis of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, affecting 0.5% to 1% of the population. It could ultimately result in joint destruction, functional decline, work disability, and enhanced mortality. Cyclic citrullinated peptide antibodies (CCP Abs) are useful biomarkers for the early detection and diagnosis of RA. In this study, we used plant viral-based expression vectors that produce rapidly large quantities of CCP-specific monoclonal antibodies. Heavy and light chain genes of a CCP monoclonal antibody (CCP mAb) were cloned from the hybridoma cell (12G1) and introduced into two separate plant viral-based expression vectors, TMV and PVX. A cyclic citrullinated peptide monoclonal antibody was produced in Nicotiana benthamiana through an Agrobacterium-mediated transient expression system. The expression of CCP mAb in tobacco plants was confirmed by dot blot, western blot analysis, and enzyme-linked immunosorbent assays (ELISA). It was shown that tobacco plants could accumulate CCP mAbs up to 0.35% of total soluble protein. Accumulated CCP mAb from infiltrated leaves was purified by protein G affinity chromatography. Immunoblot assays and ELISA showed plant-produced CCP mAbs successfully bound to a synthetic CCP peptide antigen. This system provides a fast strategy for the production of pharmaceutical CCP mAbs in tobacco plants.

Early onset of Felty syndrome or leukemia: A case report

Felty syndrome is a form of rheumatoid arthritis (RA) that usually presents with neutropenia and splenomegaly. It usually occurs in the setting of long-lasting (RA)and rarely as an early manifestation of RA. Case presentation: A 47-year-old female patient presented to the emergency department with a history of fever and arthralgia. She was found to have splenomegaly and pancytopenia. After ruling out hematologic malignancies by bone marrow biopsies, she was diagnosed with RA. Rheumatoid factor (RF) and cyclic citrullinated peptide antibody (Anti-CCP) levels were elevated. The patient was ultimately diagnosed with early-onset Felty syndrome in the course of RAand an occult hepatitis B infection. Despite the low incidence rate of Felty syndrome, it should be considered as a differential diagnosis of patients with arthralgia, fever, neutropenia, and splenomegaly.

A microfluidic platform for detection and quantification of two biomarkers for rheumatoid arthritis

Early detection of rheumatoid factors (RF) and cyclic citrullinated peptide antibodies (anti-CCP) has been proven to be effective in diagnosing, and even preventing progression to more advanced-stages, of rheumatoid arthritis (RA), thereby decreasing irreversible damage to joints. Herein a novel, dual-target detection approach was integrated in a 45 mm × 62 mm microfluidic chip that featured a symmetrical design in which magnetic beads surface-coated with fragment-crystallizable regions of immunoglobulin G and biotinylated CCP enabled detection of these two RA biomarkers within 55 min with only 5 μL of serum. This device could therefore be useful for rapid clinical diagnosis of this all-too-common ailment.

Immunosensing for Early Detection of Rheumatoid Arthritis Biomarkers: Anti-Cyclic Citrullinated Peptide Antibodies Based on Tilted-Fiber Bragg Grating Biosensor

Rheumatoid arthritis (RA) is regarded as a chronic, immune-mediated disease that leads to the damage of various types of immune cells and signal networks, followed by inappropriate tissue repair and organ damage. RA is primarily manifested in the joints, but also manifests in the lungs and the vascular system. This study developed a method for the in vitro detection of RA through cyclic citrullinated peptide (CCP) antibodies and antigens. The diameter of a tilted-fiber Bragg grating (TFBG) biosensor was etched to 50 μm and then bonded with CCP antigens and antibodies. The small variations in the external refractive index and the optical fiber cladding were measured. The results indicated that the self-assembled layer of the TFBG biosensor was capable of detecting pre- and post-immune CCP antigen and CCP peptide concentrations within four minutes. A minimum CCP concentration of 1 ng/mL was detected with this method. This method is characterized by the sensor's specificity, ability to detect CCP reactions, user-friendliness, and lack of requirement for professional analytical skills, as the detections are carried out by simply loading and releasing the test samples onto the platform. This study provides a novel approach to medical immunosensing analysis and detection. Although the results for the detection of different concentrations of CCP antigen are not yet clear, it was possible to prove the concept that the biosensor is feasible even if the measurement is not easy and accurate at this stage. Further study and improvement are required.

Relief of chest pain after SARS-CоV-2 vaccination

A 46-year-old patient consulted a cardiologist complaining of discomfort behind the sternum, which manifested itself in 3 weeks after a mild COVID-19 recovery and had been persisting for about 4 months by the time she consulted the doctor. Echocardiography did not reveal any disturbances in regional and global contractility. It was thickening and hyperechogenicity of the pericardium of the lower-lateral, and lateral areas of the left ventricle without any signs of pathological exudation that attracted attention. A chest X-ray and a test with physical activity were performed. Blood tests did not reveal any abnormality, an increase in C-reactive protein was observed. The patient was diagnosed with chronic non-exudative form of pericarditis associated with COVID-19. A successful treatment was carried out: colchicine 0.5 mg/day, ibuprofen 600 mg 3 times a day. Next time the patient consulted a doctor 3 months later. Against the background of ARVI, typical episodes of low-intensity chest pain repullulated. Echocardiography showed regional exudation and initial signs of impaired diastolic function. A compulsory vaccination with Gam-COVID-Vac was carried out in 4 weeks. The post-vaccination period was accompanied by low-grade pyrexia for 2 days, after which the patient noted the complete disappearance of the heart pain. Echocardiography recorded pericardial layers separation and some improvement in diastolic function. The treatment was not carried out for various reasons. Over the next months, cardialgia did not recur. Check study 3 months after showed no visible exudation into the pericardial cavity, a decrease in hyperechogenicity compared to the records of previous studies was noted. In 8 months after vaccination, the patient suffered another mild COVID-19 with exudative pericarditis recurrence and the involvement of the pleura. Blood tests taken during the 1st week of the disease revealed a characteristic cellular shift (lymphocytosis 38%), as well as an increase in ERS up to 26 mm/h, D-dimer up to 1166 μg/l. CRP was normal. Additional analysis for cardiolipin antibodies, antinuclear factor, rheumatoid factor, cyclic citrullinated peptide antibodies, b2 glycoprotein I antibodies did not reveal any pathology. Transient low-grade pyrexia had been persisting for 3 weeks in evening hours, in spite of the fact that she kept taking 800 mg of ibuprofen per day. By now, the patient continues receiving colchicine according to the planned 6-months course of administration.

Interpreting Rheumatology Laboratory Tests

Interpreting Rheumatology Laboratory Tests

Mechanistic and therapeutic links between rheumatoid arthritis and diabetes mellitus.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and irreversible cartilage and bone damage. Despite its predominant osteoarticular and periarticular manifestations, RA is also a systematic disease associated with organ-specific extra-articular manifestation. Increasing evidence indicates that RA patients are susceptible to diabetes mellitus (DM), and RA aggravates metabolic disordered in DM, indicating the close association between RA and DM. Many factors involved in RA stimulate insulin resistance and DM development. These factors include proinflammatory cytokines (such as TNF-α, IL-6, IL-1β), RA autoantibodies (such as rheumatoid factor, cyclic citrullinated peptide antibodies), excess RA related adipokines (such as leptin, resistin, ANGPTL4), C-creative protein, and other protein (such as TXNDC5, NLRP3, RBP4). Furthermore, commonly used RA drugs, such as conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological disease-modifying antirheumatic drugs (bDMARDs), and glucocorticoids, provide potential benefits in improving insulin resistance and inhibiting DM development. This review discusses the mechanistic and therapeutic links between RA and DM, aiming to provide valuable information for the prevention and treatment of DM in RA patients.

Relationship of cytokine level dynamics with longterm results of early rheumatoid arthritis therapy

The aim of the work – to research the relationship between the dynamics of cytokine levels in the early period (the first 12 and 24 weeks) of pharmacotherapy for rheumatoid arthritis (RA) and long-term outcomes in patients with the disease.Material and methods. The analysis included 93 patients with early RA. The majority of patients were women (n=77), middle-aged (58 [49; 66] years), with an early stage of the disease (the duration of the disease is 7 [4–11.5] months), seropositive according to IgM rheumatoid factor and cyclic citrullinated peptide antibodies, who had high (59.7%) or moderate (38.8%) disease activity.The concentration of 27 cytokines in the blood serum was determined with the help of multiplex xMAP technology on the Bio-Plex array system analyzer (BIORAD, USA). Repeated clinical examination of patients was carried out after 6 years.Results. Patients who achieved remission/low disease activity SDAI after 6 years had a lower level of IL-6 (7.7 [7.4; 23.3]), IL-9 (13.5 [9.1; 18.9]) 12 weeks after the start of therapy; lower IL-9 level (12.6 [6.8; 16.2]) 24 weeks after the start of the treatment, compared with the group of patients with moderate and high inflammatory activity (23.5 [12.4; 69.5], 17.8 [15; 29] and 18.5 [14.2; 22.8] respectively).Findings. The assessment of the level of proinflammatory cytokines (IL-6, IL-17), immunoregulatory cytokine IL-9 allows to evaluate the activity of the disease more fully and identify a group of patients, who needs the therapy intensification.

Comparative clinical characteristics of untreated early rheumatoid arthritis in patients with early and late onset according to the All-Russian Register of Patients with Arthritis “OREL”

The question about the peculiarities of the course of rheumatoid arthritis in different age periods was raised in the literature repeatedly and the answer depended on the period of development of rheumatology and was not unambiguous. The course of age-specific features of the initial stages of disease development has also been studied (although less frequently). At the same time, the issues of age-related features of as yet untreated early rheumatoid arthritis have not been previously presented in the literature studied by the authors. This article gives a brief overview of the problem and discusses the findings.The aim of the present study was the comparative study of the characteristics of untreated early rheumatoid arthritis with early (18–49 years) and late (50 years and older) onset.The material was represented by 292 patients with rheumatoid arthritis with disease duration from 1 to 12 months from the disease onset, entered into the All-Russian Register of Patients with Inflammatory Arthritis “OREL” in the period from January 01, 2012 to December 31, 2018 with the results of examination at the time of the first examination. All patients were naïve to treatment with basal (synthetic, biological or other targeted) drugs and systemic glucocorticoid therapy. In 141 patients, the disease started at a younger age, group 1 (18–49 years), and in 151, at an older age (50 years or older), group 2.Methods. Disease activity (according to DAS-28 index), radiological stage – (according to Steinbroker, modified), functional disorders – according to functional class, immunological characteristic and additional immunological characteristic (rheumatoid factor, cyclic citrullinated peptide antibodies) and other parameters were estimated in accordance to requirements of current national rheumatoid arthritis classification. The results of the study indicate that the disease in older age is characterized by more pronounced inflammatory, destructive changes in relation to the joint apparatus and functional disorders than the onset of rheumatoid arthritis at a young age.

Периферійна нейропатія при хламідійному реактивному артриті

Актуальність: периферійна нейропатія (ПНП) при реактивному хламідійному урогенітальному артриті (РХА) описується у вигляді поодиноких спостережень, і багато клініко-патогенетичних аспектів такого ураження нервової системи залишаються нез’ясованими. Мета дослідження: оцінити частоту й характер перебігу ПНП при РХА, взаємозв’язок нервових та суглобових ушкоджень, вивчити питання патогенетичних побудов цієї нейропатії, виділити чинники ризику. Матеріал і методи. Під наглядом перебував 101 хворий на РХА, середній вік яких становив 32 роки, тривалість захворювання — 4 роки, а співвідношення чоловіків і жінок — 1 : 1. У 90 % спостережень РХА виявлено Chlamydia trochamatis у секреті передміхурової залози, зіскобах з уретри, шийки матки, стінок піхви, у 83 % — позитивні серологічні тести на хламідійну інфекцію. Результати. При РХА ознаки ПНП мають місце в 19 % хворих у співвідношенні мононейропатія/полінейропатія як 1 : 1, із моторними, сенсорними і змішаними розладами в пропорції 1 : 3 : 6, наявністю вегетативних змін у кожного другого пацієнта та частішою дистальною локалізацією процесу в руках, на що впливають тяжкість перебігу суглобового синдрому, високі рівні протихламідійних антитіл у крові, а на аксональні й демієлінізуючі показники електронейроміографії — вираженість уражень урогеніталій і наявність синдрому Гійена — Барре. Високий показник темпів прогресування артриту є прогнознегативною ознакою перебігу ПНП у хворих на РХА. У патогенетичних побудовах ПНП беруть участь запальні імунні білки, порушення ендотеліальної функції судин та фізико-хімічні поверхневі реологічні властивості сироватки. Висновок. ПНП має місце в кожного п’ятого пацієнта з РХА, взаємопов’язана з клініко-лабораторними ознаками уражень суглобів, а в майбутньому буде корисним активне виявлення такої патології нервової системи для подальших своєчасних реабілітаційних заходів, причому серопозитивність РХА за антитілами до циклічного цитрулінового пептиду є чинником ризику такої ПНП.