Cyclic Citrullinated Peptide Antibodies Research Articles

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<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.

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 < 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 < 0.05) in the RA group. Whereas no significant correlation (P > 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 < 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 <i>Helicobacter pylori</i> 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 < 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 < 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.

OP0251 IMPACT OF INTERSTITIAL LUNG DISEASE ON SEVERE COVID-19 OUTCOMES FOR PATIENTS WITH RHEUMATOID ARTHRITIS: A MULTICENTER STUDY

BackgroundRA has been associated with poor COVID-19 outcomes, but few studies have investigated outcomes in RA features such as interstitial lung disease.ObjectivesTo assess COVID-19 outcomes in patients with RA overall, and those with and without ILD, compared to general population comparators.MethodsA multicenter, retrospective cohort study was conducted at Mayo Clinic (19 hospitals and affiliated outpatient centers in 4 states) and Mass General Brigham (14 hospitals and affiliated outpatient centers in New England). Consecutive patients with RA meeting ACR/EULAR criteria and a positive COVID-19 test from March 1, 2020 through June 6, 2021 were matched 1:5 on age, sex, race, and COVID-19 test date with general population comparators without RA. RA features assessed included: RA-ILD per Bongartz criteria [1], duration, rheumatoid factor (RF), cyclic citrullinated peptide antibody (CCP), bone erosions, and treatments. The primary outcome was a composite of hospitalization or death following COVID-19 diagnosis. We used multivariable Cox regression to investigate the association of RA, and features such as ILD, with COVID-19 outcomes compared to matched comparators.ResultsWe analyzed 582 patients with RA and 2892 comparators without RA, all with COVID-19. Mean age was 62 years, 51% were female, and 79% were White. Mean RA duration was 11 years, 67% were seropositive (52% RF+ and 54% CCP+), 27% had bone erosions, 28% were on steroids, and 79% were on DMARDs. 50/582 (9%) patients with RA had ILD.The COVID-19 hospitalization or death rate for RA patients was higher than comparators (3.0 per 1,000 days [95% CI 2.5-3.6] vs. 1.9 per 1,000 days [95% CI 1.7-2.1], respectively). Overall, RA patients had a 53% higher risk of hospitalization or death than comparators after adjustment (95% CI 1.20-1.94).Among those with RA-ILD, the hospitalization or death rate was significantly higher than comparators (10.9 [95% CI 6.7-15.2] vs. 2.5 per 1,000 days [1.8-3.2], respectively). RA-ILD was associated with nearly 3-fold higher risk for hospitalization or death than comparators (multivariable HR 2.84 [95% CI 1.64-4.91], Table 1). There was a significant interaction between RA/comparator status and presence/absence of ILD for risk of severe COVID-19 (p<0.001, Figure 1). The elevated risk for severe COVID-19 was similar for RA subgroups defined by serostatus or bone erosions.Table 1.Frequencies, proportions, and hazard ratios for COVID-19 outcomes, comparing all RA patients, and subgroups with or without RA-ILD, to matched comparators.COVID-19 OutcomesAll RA Patients (n=582)RA-ILD (n=50)RA Patients without ILD (n=532)Comparators (n=2,892)Hospitalization, n (%)121 (21)24 (48)97 (18)402 (14)Unadjusted HR (95% CI)1.58 (1.27, 1.96)2.65 (1.71, 4.09)1.43 (1.12, 1.82)Ref.Adjusted* HR (95% CI)1.45 (1.14, 1.83)2.35 (1.38, 4.00)1.31 (1.00, 1.70)Ref.Death, n (%)26 (4)9 (18)17 (3)63 (2)Unadjusted HR (95% CI)1.72 (0.98, 3.01)5.88 (2.07, 16.71)1.13 (0.56, 2.29)Ref.Adjusted* HR (95% CI)1.24 (0.66, 2.32)13.94 (4.30, 45.18)0.75 (0.35, 1.63)Ref.Hospitalization or death, n (%)126 (22)25 (50)101 (19)419 (14)Unadjusted HR (95% CI)1.66 (1.33, 2.07)3.01 (1.93, 4.70)1.47 (1.14, 1.89)Ref.Adjusted* HR (95% CI)1.53 (1.20, 1.94)2.84 (1.64, 4.91)1.34 (1.02, 1.77)Ref.*Adjusted for age, sex, race, and smokingFigure 1.Multivariable hazard ratios for the composite outcome of hospitalization or death from COVID-19, comparing all RA and subgroups by serostatus, bone erosions, and ILD to matched comparators without RA.ConclusionWe confirmed that RA was associated with severe COVID-19 outcomes compared to the general population. We found evidence that ILD may be an effect modifier for the relationship between RA and severe COVID-19 outcomes, but RA subgroups defined by serostatus and bone erosions had similarly elevated risk. These findings suggest that ILD or its treatment may be a major contributor to severe COVID-19 outcomes in RA.

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.

Rheumatoid Arthritis: Brief Overview of Diagnosis and Treatment along with Disease Management

Background: Rheumatoid Arthritis (RA) is a multisystem illness specifically marked through chronic distension and joint destruction. Time of life, gender, heredity, and ecological familiarity are risk factors (cigarette smoking, air contaminants, and industrial). If left untreated, Felty disorder can lead to permanent joint damage needing arthroplasty, rheumatic vasculitis, rheumatic vasculitis, and rheumatic vasculitis necessitating splenectomy. Because RA is noncurable, the focus of action is on reducing discomfort and preventing additional damage via rest. In this article, I provide a brief overview of various previous and current reporting mechanisms for RA-related issues.
 Description: RA is a debilitating, long-term illness that can cause joint deterioration and incapacitating symptoms. Initial analysis, in addition to participation, is crucial in preventing grave damage and the forfeiture of dynamic bodily roles. Autoantibodies including rheumatoid factor (RF) and anti cyclic citrullinated peptide antibodies (anti-CCP) have a longstanding experience of therapeutic specificity, and they can correctly predict RA in patients with UA. Furthermore, a few experimental otherwise radiological features on the reference line might predict RA progression in the future.
 Significance: Rheumatoid Arthritis affects the joints and the internal organs, resulting in incapacity in a variety of instances. There is currently no definable treatment for this autoimmune disease. The conventional and current coping choices available for monitoring impacted, suffering from this complex illness is succinctly outlined at this point.

P010 Clinico-epidemiological characteristics and outcomes of Juvenile Idiopathic Arthritis (JIA) patients in Kenya: data from the KAPRI registry

Abstract Background Pediatric rheumatic diseases pose a significant disease burden upon children and their families (1–3). They lead to physical disability and diminished quality of life (1–3). Determination of the burden and clinical characteristics of these diseases is a critical first step to improving access to care and optimizing use of existing health systems for the well-being of these patients (4). This is in line with the goal of the Bone and Joint decade (2000–2010) aimed at increasing recognition and understanding of the impact of musculoskeletal diseases (5,6). The Kenya Pediatric Rheumatology Registry (KAPRI) offers a unique opportunity to pioneer and spearhead a systematic and organized format to inform policy and better healthcare provision. Our objective was to determine the patient characteristics, clinical features and outcomes of Juvenile Idiopathic Arthritis (JIA) patients assessed at the Aga Khan University Medical College East Africa from March 2019 to December 2020. Methods Data of JIA patients on age, gender, laboratory and clinical features at diagnosis and treatment options offered were extracted from the database. A further detailed chart review was undertaken to determine the proportion of patients who achieved remission or minimally active diseases. Results Among the 207 patients enrolled thus far, 16 (7.7%) were diagnosed to have JIA. Majority of the patients were females (75%; n = 12) with a mean age of 7 years and 3 months (Range : 1 year—13 years 7 months). All patients had joint pain and swelling as the initial presenting complaints. Majority of the patients had polyarticular JIA (75%, n = 12). The other 4 patients were oligoarticular (n = 2) and systemic JIA (n = 2). Among the polyarticular JIA patients (n = 12), only 3 (25%) were rheumatoid factor (RF) positive and 1 was antinuclear antibody (ANA) positive. The oligoarticular and systemic JIA patients were all negative for antinuclear antibody, rheumatoid factor and cyclic citrullinated peptide antibodies (anti-ccp). Seven patients (43.8%) required biological therapies; tocilizumab (n = 2: systemic JIA), adalimumab (n = 2: polyarticular JIA), etanercept (n = 2: polyarticular JIA) andtofacitnib (n = 1: polyarticular JIA). One patient with systemic JIA on tocilizumab developed herpes simplex which was successfully managed with oral acyclovir. All the other patients did not develop any infections, allergic reactions or any other untoward events as adverse outcomes following the use of biological therapies. Five patients have attained remission as illustrated in the table below. Two patients have been lost to follow up. Conclusion Seronegative polyarticular JIA was the predominant form of JIA observed with a predilection to affect more girls and boys. Over a period of 2 years, remission has been attained among 31.25% of the patients (5 of 16) with use of synthetic disease modifying anti-rheumatic drugs and biological therapies.

Содержание кремния в крови и синовиальной жидкости больных ревматоидным артритом: клинико-патогенетическая значимость микроэлементоза

Актуальность. Распространенность ревматоидного артрита (РА) среди населения земного шара составляет около 1 %, а среди отдельных популяций людей достигает 5–7 %. К факторам риска развития и высоких темпов прогрессирования РА относятся большие концентрации во вдыхаемом воздухе кварца (диоксида кремния), токсическое воздействие которого рассматривается как один из мощных патогенетических факторов этого заболевания. Цель. Оценка клинико-патогенетической значимости кремниевого микроэлементоза при РА. Материалы и методы. Обследованы 83 больных РА (22 % мужчин и 78 % женщин в возрасте от 22 до 75 лет; в среднем 45 лет). Длительность заболевания от первых признаков его манифестации составила 9 лет. Системная форма болезни диагностирована в 19 % случаев, серопозитивный РА по ревматоидному фактору установлен в 68 % наблюдений, по антицитруллиновым антителам — в 80 %. Содержание кремния (Si) в сыворотке крови и синовиальной жидкости у 19 больных определяли с помощью атомно-абсорбционного спектрометра SolAAr-Mk2-MOZe с электрографитовым атомизатором (Великобритания). С использованием компьютерного тензиометра PAT2-Sinterface (Германия) исследовали параметры поверхностного натяжения сыворотки крови и синовиальной жидкости при времени «жизни поверхности» 0,01 с, стремящемся к бесконечности, подсчитывали их соотношение. Результаты. РА сопровождается отсутствием достоверных изменений уровня кремниемии. Микроэлементоз Si связан с клиническими, рентгенологическими и сонографическими признаками течения заболевания, степенью активности и тяжестью артрита, а кремниевый дисбаланс участвует в патогенетических построениях суставного синдрома, поражении скелетных мышц, периферической нервной системы, причем показатели Si в крови могут обладать прогностической значимостью.

INTERSTITIAL LUNG DISEASE AS THE ONLY MANIFESTATION OF RHEUMATOID ARTHRITIS: CAN LUNGS BE THE SITE OF ORIGIN FOR RHEUMATOID ARTHRITIS-RELATED INFLAMMATION?

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Rheumatoid Arthritis (RA) is a systemic inflammatory disease primarily involving joints. Extra-articular manifestations of RA without joint disease are extremely rare. Lung disease represents a second common cause of death in RA after cardiovascular events (1). RA related lung disease includes interstitial lung disease (ILD), bronchiectasis and pleural disease. We report a patient with severe progressive RA related ILD, usual interstitial pneumonia (UIP) phenotype without joint involvement and poor outcome. CASE PRESENTATION: A 67-year-old female with one-year history of seropositive rheumatoid arthritis without joint involvement, on methotrexate presented with worsening shortness of breath. The exertional dyspnea started two years ago, and a screening low dose CT chest showed mild fibrotic changes at lung bases prior to methotrexate initiation. This time HRCT revealed progressive interstitial lung disease-usual interstitial pneumonia pattern, bilateral honeycombing of the lung bases and traction bronchiectasis. Pulmonary function test revealed restrictive ventilatory and severe gas transfer defect. Rheumatoid factor (RF) and Cyclic Citrullinated Peptide antibody (IgG) were 99.6 and above 250 respectively. ANA titer was low at 1:40, speckled pattern with normal ANCA. Methotrexate was discontinued and prednisone was started. She was discharged home on oxygen therapy but continued to decompensate with progressive hypoxemic respiratory failure eventually requiring high flow nasal canula. Repeat HRCT showed new ground glass opacities on left along with baseline interstitial changes. Flexible bronchoscopy with bronchoalveolar lavage showed no evidence of infection or malignancy. Patient was started on pulse dose steroids for possible ILD flare. However, her oxygen requirement and symptoms continued to worsen, and she was started on Mycophenolate Mofetil. With no improvement patient eventually opted for home hospice. DISCUSSION: Risk factors associated with RA-related ILD include older age, male sex, smoking and seropositivity for RF or anti-CCP antibodies. In addition, women with seropositive RA have increased risk of lung involvement than women without RA (2). Our patient presented with rapidly progressive ILD-UIP type without any joint disease and poor outcome. Methotrexate was less likely a culprit given the interstitial fibrotic changes present before drug initiation and rapid progression of ILD despite drug cessation. In our case lungs seem to be the primary site of RA related inflammation in setting of smoking causing citrullination of proteins and autoimmune responses (2). CONCLUSIONS: Although data on identification, management staging or monitoring of RA-related ILD without joint disease is lacking, clinicians should remain vigilant of this complication. RA-related UIP is more frequent with progressive disease and poor outcome and warrants early recognition and treatment (3). REFERENCE #1: G. Cafaro, A. Alunno, V. Valentini, M.C. Leone, E. Marcucci, E. Bartoloni, R. Gerli. The onset of rheumatoid arthritis: the joints or the lung? Reumatismo, 2016; 68 (4): 167-175 REFERENCE #2: Paolo Spagnolo, Joyce S. Lee, Nicola Sverzellati, Giulio Rossi, Vincent Cottin. The lung in Rheumatoid Arthritis. Focus on Interstitial Lung Disease. ARTHRITIS & RHEUMATOLOGY Vol. 70, No. 10, October 2018, pp 1544-1554 DOI 10.1002/art.40574 American College of Rheumatology REFERENCE #3: Hyun-Kyung Lee, MD; Dong Soon Kim, MD; Bin Yoo, MD; Joon Beom Seo, MD; Jae-Yoon Rho, MD; Thomas V. Colby, MD; Masanori Kitaichi, MD. Histopathologic Pattern and Clinical Features of Rheumatoid Arthritis-Associated Interstitial Lung Disease (CHEST 2005; 127:2019-2027) DISCLOSURES: No relevant relationships by Maria Azhar, source=Web Response No relevant relationships by Fatima Halilu, source=Web Response No relevant relationships by Qasim Muhammad, source=Web Response No relevant relationships by Matthew Woodford, source=Web Response