Exacerbation Of Arthritis Research Articles

Epstein-Barr Virus DNA Exacerbates Arthritis in a Mouse Model via Toll-like Receptor 9.

Epstein-Barr virus (EBV) DNA is known to be shed upon reactivation of latent EBV. Based on our previous findings linking Toll-like receptor-9 (TLR9) to an EBV DNA-driven surge in IL-17A production, we aimed to examine the therapeutic potential of TLR9 inhibition in EBV DNA-exacerbated arthritis in a collagen-induced arthritis (CIA) mouse model. C57BL/6J mice were administered either collagen, EBV DNA + collagen, EBV DNA + collagen + TLR9 inhibitor, or only the TLR9 inhibitor. After 70 days, paw thicknesses, clinical scores, and gripping strength were recorded. Moreover, affected joints, footpads, and colons were histologically scored. Furthermore, the number of cells co-expressing IL-17A, IFN-γ, and FOXP3 in joint sections was determined by immunofluorescence assays. Significantly decreased paw thicknesses, clinical scores, and histological scores with a significantly increased gripping strength were observed in the group receiving EBV DNA + collagen + TLR9 inhibitor, compared to those receiving EBV DNA + collagen. Similarly, this group showed decreased IL-17A+ IFN-γ+, IL-17A+ FOXP3+, and IL-17A+ IFN-γ+ FOXP3+ foci counts in joints. We show that inhibiting TLR9 limits the exacerbation of arthritis induced by EBV DNA in a CIA mouse model, suggesting that TLR9 could be a potential therapeutic target for rheumatoid arthritis management in EBV-infected individuals.

Chronic cold environment regulates rheumatoid arthritis through modulation of gut microbiota-derived bile acids

The pathologies of many diseases are influenced by environmental temperature. As early as the classical Roman age, people believed that exposure to cold weather was bad for rheumatoid arthritis (RA). However, there is no direct evidence supporting this notion, and the molecular mechanisms of the effects of chronic cold exposure on RA remain unknown. Here, in a temperature-conditioned environment, we found that chronic cold exposure aggravates collagen-induced arthritis (CIA) by increasing ankle swelling, bone erosion, and cytokine levels in rats. Furthermore, in chronic cold-exposed CIA rats, gut microbiota dysbiosis was identified, including a decrease in the differential relative abundance of the families Lachnospiraceae and Ruminococcaceae. We also found that an antibiotic cocktail suppressed arthritis severity under cold conditions. Notably, the fecal microbiota transplantation (FMT) results showed that transplantation of cold-adapted microbiota partly recapitulated the microbiota signature in the respective donor rats and phenocopied the cold-induced effects on CIA rats. In addition, cold exposure disturbed bile acid profiles, in particular decreasing gut microbiota-derived taurohyodeoxycholic acid (THDCA) levels. The perturbation of bile acids was also associated with activation of the TGR5-cAMP-PKA axis and NLRP3 inflammasome. Oral THDCA supplementation mitigated the arthritis exacerbation induced by chronic cold exposure. Our findings identify an important role of aberrant gut microbiota-derived bile acids in cold exposure-related RA, highlighting potential opportunities to treat cold-related RA by manipulating the gut microbiota and/or supplementing with THDCA.

The interplay between Epstein-Barr virus DNA and gut microbiota in the development of arthritis in a mouse model.

Epstein-Barr virus (EBV) DNA may influence the development of autoimmune diseases by increasing the production of proinflammatory cytokines. Such cytokines have been associated with inducing the dysbiosis of colonic microbiota, which, in turn, is a risk factor for autoimmune diseases such as rheumatoid arthritis (RA). Therefore, we investigated the role that EBV DNA may play in modulating the intestinal microbiota and consequent exacerbation of arthritis in a mouse model. Mice were treated with collagen (arthritis-inducing agent), EBV DNA and collagen, EBV DNA, or water. Fecal samples were collected from arthritic and control mice, and 16S rRNA sequencing was performed to determine the effect of EBV DNA on the composition of colonic microbiota. EBV DNA causes a change in the alpha diversity of the microbiota resulting in an increased Chao1 microbial richness and decreased Shannon diversity index in the RA mouse model. In addition, the abundance of particular genera/genus clusters was significantly altered among the various groups, with the EBV DNA-exacerbated arthritic group having the highest number of altered genera/genus cluster abundances. This group also had the highest number of cells co-expressing IL-17A, FOXP3, and IFNγ in the colons. Antimicrobial-cleared mice transplanted with fecal samples from EBV DNA-exacerbated arthritic mice showed a higher incidence and enhanced severity of RA compared to those transplanted with fecal samples from water or collagen-treated mice. IMPORTANCE Epstein-Barr virus (EBV) DNA alters the composition and diversity of the gut microbiota in a rheumatoid arthritis (RA) mouse model. These induced changes are associated with enhanced severity of symptoms. This better understanding of the various factors involved in the development of RA will possibly help in creating individualized treatments for RA patients including target mediators triggered by viral DNA. Given that a large swathe of the population harbors EBV, a significant proportion of subjects with arthritis may benefit from possible approaches that target EBV or mediators triggered by this virus.

Comparison of the effects of peficitinib and tofacitinib in the adjuvant-induced arthritis rat model

We investigated and compared the pharmacologic properties of two Janus kinase (JAK) inhibitors, peficitinib and tofacitinib, in an adjuvant-induced arthritis rat model. Repeated administration of peficitinib (3 − 30 mg/kg) or tofacitinib (1 − 10 mg/kg) exhibited a dose-related and significant attenuation of arthritis score, paw swelling, pain threshold, grip strength and histopathologic injuries in the model; peficitinib 10 mg/kg and tofacitinib 3 mg/kg demonstrated comparable efficacy. Equivalent Cmax and AUC0–12h values were observed with peficitinib 10 mg/kg and tofacitinib 3 mg/kg, suggesting that the two drugs may demonstrate comparable efficacy on arthritis-associated symptoms at comparable plasma concentration levels. However, peficitinib 10 mg/kg had greater efficacy than tofacitinib 3 mg/kg on some inflammation- and bone destruction-associated parameters in the paw fluid, including the production of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), receptor activator of nuclear factor kappa-B ligand, and matrix metalloproteinase-3, which are associated with arthritis exacerbation. Peficitinib 10 mg/kg also showed significantly greater inhibitory effects than tofacitinib 3 mg/kg on loss of bone mineral density and synovial thickening score, which might be a result of the VEGF and PDGF receptor kinase inhibitory effects of peficitinib, in addition to JAK inhibition. In conclusion, both tofacitinib and peficitinib potently improved arthritis and associated symptoms in adjuvant-induced arthritis rats; moreover, owing to possible differences in the mechanism of action of the two drugs, peficitinib may have exerted its effects through JAK inhibition and additional unique off-target properties.

Role of Rehabilitation in Comprehensive Management of Juvenile Idiopathic Arthritis: When and How?

Juvenile idiopathic arthritis (JIA), the most common chronic rheumatological disorder in children, can result in significant disability and poorer health-related quality of life. Rehabilitation aimed at pain management, optimizing musculoskeletal function, improving endurance and achieving independence in activities of daily living, and participation in age-appropriate activities, is a vital component in the comprehensive management of children with this condition. Rehabilitation strategies depend on the phase of the disease and focus on pain alleviation in the active phase and improving mobility and function in the inactive phase. Rehabilitation in JIA is multidisciplinary and includes exercise therapy, physical modalities, orthotic and assistive devices, and gait training. Exercise therapy has demonstrated improvement in muscle strength, bone mineral density, exercise capacity, and quality of life, without negative consequences of pain or exacerbation of arthritis. Common exercise interventions for children with JIA include mobilization, strengthening, aerobic exercises, Pilates-based exercises, aquatic therapy, and recreation. Physical modalities such as thermotherapy, cryotherapy, electrotherapy, ultrasound, and low-power laser therapy are commonly employed. Orthotic devices play an important role in joint protection, prevention and reduction of joint deformities, and assistance with function and gait. Assistive devices are prescribed to improve functional ability and independence in activities of daily living in children with disabilities. There have been recent advances in the field of rehabilitation with the advent of robotics, virtual reality, and telerehabilitation.

Immunogenicity and Safety of the BNT162b2 mRNA COVID-19 Vaccine in Patients with Melanoma Treated with Immunotherapy.

Simple SummaryThe efficacy and safety of the BNT126b2 vaccine against SARS-CoV-2 has not been thoroughly studied in cancer patients treated with immunotherapy. This research aims to investigate the efficacy and safety of the vaccine in patients with melanoma under immunotherapy; at the same time, through the immunophenotyping of T cells and myeloid cells of the peripheral blood, it will be possible to look for changes in the subpopulations of such cells after vaccinations. The results of the study help establish the efficacy and safety of the vaccine in this population, especially since a theoretical concern exists about the vaccine triggering irAEs.The BNT162b2 vaccine against SARS-CoV-2 has a proven efficacy and a favorable safety profile. In cancer patients under immunotherapy in the form of immune-checkpoint inhibitors (ICIs), the efficacy of the vaccine has not been thoroughly studied, while a theoretical concern has also been raised about triggering immune-related adverse events (irAEs) by the vaccine. We conducted a prospective, non-interventional study on the immunogenicity and safety of the BNT162b2 vaccine in patients with advanced or metastatic melanoma treated with ICIs. Blood samples were obtained 0–4 days before the first dose and 12–21 days after the second dose of the vaccine for the quantification of the SARS-CoV-2 anti-spike antibody using an ELISA and immunophenotyping of the T and myeloid cell subpopulations. The active recording of AEs for a two-month period was conducted. Forty patients were included in the study. All but one (97.3%) achieved seroconversion after two doses of the vaccine and no correlations of the antibody titers with any of the studied parameters (age, gender, stage and duration of the disease, type of ICI, previous treatment, etc.) were found. Moreover, no differences in the subpopulations of the T cells (including the T-regulatory cells) or the myeloid cells were found pre- and post-vaccination. All AEs were low-grade, while one case of arthritis exacerbation was noted. The seroconversion rate in the studied population was high and was comparable to that of healthy subjects, while no major safety issues were raised during the safety follow-up. Finally, no derangements in the subpopulations of T cells or myeloid cells were noted. This is the first study focusing on the immunogenicity, safety, and effect of anti-SARS-CoV-2 vaccines on the blood-cell immunophenotype status of patients with melanoma treated with ICIs.

The Effect of Inhaled Air Particulate Matter SRM 1648a on the Development of Mild Collagen-Induced Arthritis in DBA/J Mice

Air pollution is considered to be one of a risk factor for rheumatoid arthritis (RA). Collagen-induced arthritis (CIA) is commonly used as a mouse model of human RA. However, the impact of specific particulate matter (PM) components on the incidence and severity of RA has still not been established. The aim of this study was to develop an experimental model of CIA suitable to test arthritogenicity of inhaled PM. A mild form of CIA was induced in DBA1/J mice inhaled with various components of SRM 1648a PM. The incidence and severity of arthritis was assessed, and the selected serum markers of autoimmunity and inflammation were determined. Clinical arthritis was observed from the booster CII immunisation onward. Anti-cyclic citrullinated peptide antibodies, a diagnostic marker of RA, were detected in serum of these mice. All inhaled pollutants, crude PM, PM with reduced organic content, ferric, and silica nanoparticles markedly increased CIA incidence and severity. The fastest progression of CIA development was caused by crude PM and was linked to enhanced serum levels of anti-CII IgG, the prominent arthritogenic autoantibodies. On the other hand, inhaled nanoparticles enhanced serum levels of TNFα, a major proinflammatory arthritogenic cytokine. We recommend this experimental model of mild CIA to test the mechanisms of arthritis exacerbation by inhaled air pollutants. Further studies are necessary to determine whether PM-aggravated arthritis is caused by inflammatory mediators translocated from inflamed lung into systemic circulation or whether PM translocated into the bloodstream directly exacerbate joint inflammation.

Colchicine for the treatment of COVID-19: short path from theory to practice

Colchicine is an alkaloid isolated from plants of the Colchicum genus. Colchicine has been used for thousands of years and remains one of the few drugs whose use remains relevant today. The therapeutic use of colchicine is widely known for gout, familial Mediterranean fever, Behcet’s disease, cardiovascular diseases (pericarditis, coronary heart disease, pericarditis, after coronary artery bypass grafting, etc.) and other diseases and is due to anti-inflammatory effects, which are based, including , inhibition of NLRP3 inflammasome and interleukin (IL)-1β production. The mechanisms of anti-inflammatory action of colchicine are diverse. It is primarily an inhibitor of mitosis and microtubule assembly. Colchicine destroys the structure of microtubules and reduces the elasticity and relaxation of neutrophils, thereby preventing the extravasation of neutrophils from blood vessels to the site of inflammation. Systemic inflammation is also a hallmark of coronavirus disease (COVID-19), which develops immunological disorders accompanied by the production of a large number of pro-inflammatory cytokines, including interleukin-1. Coronavirus disease 2019 (COVID-19), which has become the most urgent medical problem in the world in the last 2 years, given the mechanisms of inflammation similar to rheumatic diseases, is also considered a disease with the potential effectiveness of colchicine treatment. SARS-CoV-2 vaccines also have a trigger factor for the development of an exacerbation of arthritis. On average, colchicine use was associated with a 47% reduction in post-vaccination arthritis. This article provides an update on the mechanisms of action and current experience with colchicine in COVID-19, including in patients with microcrystalline arthritis.

Long-term outcomes of open arthrolysis combined with radial head arthroplasty for post-traumatic elbow stiffness: results are durable over 8 years.

Post-trauma elbow stiffness (PTES) is a common complication after elbow trauma that causes severe upper limb disability. Open elbow arthrolysis (OEA) with radial head arthroplasty (RHA) is an effective method to treat PTES with rotation limitation, or persistent pain/instability after radial head resection. However, no long-term results have been reported for this technique. This study aimed to show the clinical and radiographic outcomes of OEA with RHA over 8 years and compare its efficacy at 3 years (short-term). Patients with PTES treated by OEA with RHA between September 2010 and December 2012 were retrospectively reviewed. Seventeen patients were followed up over 8 years (range, 100-106 months). A bipolar prosthesis of RHA was performed during OEA. Preoperative, 3-year, and 8-year elbow and forearm motion, upper limb function, radiographic outcomes, and complications were recorded. Clinically important improvements in elbow motion and forearm rotation were obtained, from 34° and 58° preoperatively, to 109° and 135° at 3 years, which were maintained over 8 years, to 113° (P = .262) and 134° (P = .489). The Mayo Elbow Performance Index had clinically important increases from the preoperative level of 58 to 94 points at 3 years, and was maintained over 8 years (95 points, P = .422), with 100% reporting excellent to good outcomes. Pain and nerve symptoms were also improved. Complications consisted of new-onset ulnar nerve symptoms in 1 patient, nonclinically significant heterotopic ossification recurrence in 3, humeroulnar arthritis exacerbation in 4, and periprosthetic lucency in8. OEA with RHA yielded satisfactory short-term outcomes for PTES at 3 years, with substantial improvements in elbow mobility and function, and the results were durable over the long term (8 years).

Modern facilities of pharmacological correction of hyperuricemia in rheumatic diseases: management of difficult clinical cases

The article presents clinical cases of management of patients with low compliance with treatment, suffering from rheumatic diseases and disorders of purine metabolism.Cases report 1. The first patient with advanced gout, after taking 100 mg of allopurinol, developed undesirable effects: sore throat, change in voice, cough, and therefore treatment was discontinued. After six months without therapy, the condition worsened and, in self-medication, the patient resumed taking allopurinol at a dose of 300 mg per day, which, as expected, resulted in a resumption of the allergic reaction and a serious exacerbation of gouty arthritis. In order to stop continuous relapses of arthritis, it became necessary to prescribe glucocorticoids. After stabilization of the state, constant administration of febucostat with positive clinical and laboratory dynamics was recommended.Cases report 2. The second patient with rheumatoid arthritis (RA) developed analgesic nephropathy, secondary hyperuricemia, and typical gouty attacks in the background of high activity of the underlying disease, existing kidney pathology and inappropriate use of non-steroidal anti-inflammatory drugs (NSAIDs). Frequent exacerbations of arthritis prompted the patient to finally see a rheumatologist. The adjusted therapy made it possible to reduce RA activity, reach the recommended level of uric acid, and reduce the drug load on the kidneys with almost complete withdrawal of NSAIDs. Thus, in modern conditions, rheumatologists have in reserve all the necessary means for the pharmacological correction of hyperuricemia, even in difficult clinical cases. Febucostat is the drug of choice for correcting uric acid levels in case of intolerance to allopurinol, as well as in the development of secondary gout against the background of renal failure. In addition, it should be noted that the effectiveness of the treatment of rheumatic diseases largely depends on the patient’s compliance. To increase adherence to therapy, regular patient schools are recommended.

Neurological involvement in secondary hemophagocytic lymphohistiocytosis in children.

To describe neurological characteristics and CNS involvement on MRI in secondary hemophagocytic lymphohistiocytosis (sHLH) and differentiate it from primary hemophagocytic lymphohistiocytosis (pHLH) and acute disseminated encephalomyelitis (ADEM). Nine children with sHLH who had neurological symptoms were retrospectively included. Characteristics of brain MRI were compared to those of 15 children with pHLH and neurological involvement and 44 children with ADEM. Three children (33%) presented with isolated neurological symptoms. Neurological signs occurred within one month following Epstein-Barr virus primary infection or systemic juvenile arthritis exacerbation in 8 patients (89%). Eight children (89%) had MRI lesions. sHLH MRI lesions were distinct of those of pHLH by morphology and signal with more frequent hyposignal intensities on T1-weighted sequences (p=0.01) and well-defined and less fuzzy lesions (p=0.03). All patients survived and one patient presented severe motor and cognitive disability. Neurological symptoms of sHLH are non-specific and their outcome is favorable in most of the children. MRI at onset may help to differentiate this condition from pHLH.

Colchicine for gout

Colchicine is a drug that has been known for several millennia, since the days of Ancient Egypt, but has been successfully used to treat gout to this day. The action of colchicine is based on microtubule damage, mitosis suppression, as well as the ability to inhibit the activation of NLRP3 inflammasoma by monosodium urate crystals and block the release of interleu-kina (IL)-1p - key cytokine in the development of gout inflammation. However, the mechanism of action of colchicine is still not fully understood.Colchicine should be considered as the optimal drug not only for relieving an acute attack of arthritis in gout, but also as the best method for preventing attacks of gouty arthritis when choosing urate-lowering therapy. Recent studies have confirmed the good efficacy and safety profile of the drug when used correctly in patients with gout. Currently, it is recommended to use low doses of the drug (1-1.5 mg per day to relieve an acute attack of arthritis and 0.5-1.0 mg to prevent attacks when initiating uratelowering therapy). At the same time, according to the results of recent studies on the effectiveness, low doses are not inferior to high doses, but when low doses are used, the frequency of undesirable effects is much less. Unlike non-steroidal anti-inflammatory drugs and glucocorticoids, the drug does not have a negative effect on the cardiovascular system and can be used in patients with diabetes mellitus. This allows the drug to be used for a long time, which is especially important, since it is recommended to prevent arthritis attacks for at least 6 months from the start of taking urate-lowering drugs. This avoids the exacerbation of arthritis in most patients and significantly reduces their frequency. In addition, in the light of the accumulating data on the effect of the drug on the cardiovascular system of the drug, in conjunction with the high safety profile, other points of application should be considered where both anti-inflammatory and cardioprotective properties of colchicine can be used.

Bone changes in early inflammatory arthritis assessed with High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT): A 12-month cohort study.

Erosion development is of crucial significance as it impacts prognosis and therapy decisions in patients with inflammatory joint diseases. Our study aimed to determine the sensitivity of high-resolution peripheral quantitative computed tomography (HR-pQCT) to detect change of bone surface over time and to identify erosion development in early inflammatory arthritis (EIA) patients. Moreover, the contribution of prognostic factors on periarticular bone damage in the first year of diagnosis assessed by HR-pQCT was explored. 46 patients with arthritic symptoms for less than one year, and a clinical diagnosis of inflammatory arthritis were prospectively imaged at baseline and 12-months. HR-pQCT scans of the 2nd and 3rd MCP joints and CR of the hands and feet were performed. Joint space width (JSW), total bone mineral density (Tt.BMD), erosion presence and volume were assessed with HR-pQCT. Scan-rescan precision was assessed to define an individual-level least significant change (LSC) criterion. Regression analyses explored prognostic factors for bone damage progression. We observed no significant group-level changes in JSW, Tt.BMD or erosion volume. 20% or fewer joints demonstrated individual-level changes greater than the LSC criterion for mean JSW, Tt.BMD and erosion volume. HR-pQCT detected more erosions than CR in the 2nd and 3rd MCP. Increased symptom duration at diagnosis was weakly associated (P<0.10) with lower JSW minimum and higher JSW standard deviation. Gradual degradation of JSW, proportional to symptom duration, was detected by HR-pQCT. EIA patients need to be closely monitored for exacerbation of arthritis and progression of periarticular bone damage.

Targeting both IL-17 and CXCR2 in the gut leads to the suppression of arthritis and joint inflammation in the autoimmune arthritis mice driven by a mycoplasma superantigen

Abstract Individuals with autoimmune susceptible genes infected with environmental microbial agents might amplify an autoimmune condition by either exacerbating an ongoing disorder, including a relapse, or by leading to chronic progressive disease. Previously we have established an autoimmune arthritis model by infecting mice with the Mycoplasma arthriditis. M. arthritidis produces a potent superantigen (SAg) MAM, which was found to be responsible for the arthritis resembling human RA. In the present study we found that MAM can also activate intestinal immune cells in mice. Because the mechanisms leading from systemic autoimmunity to joint-specific autoimmune disease are unknown, we questioned if the autoimmunity initiates at mucosal sites. To address this question, by injecting mice with collagen II (CII), or with CII+MAM. We found that IL-17 and chemokine receptor CXCR2 were highly expressed within the intestinal lamina propria (LP) in CII+MAM mice but not in traditional CIA mice. In CII+MAM mice, overexpression of IL-17 and CXCR2 in the gut was shown to be strongly related to the arthritis severity. Massive infiltration of inflammatory leukocytes and the upregulation of chemokines, CXCL1, CXCL2, CXCL12, CCL2 and CCL5 in the joint tissues were detected and associated with the increased IL-17 and CXCR2 in the intestinal LP following CII+MAM immunization. Suppression of both IL-17 and CXCR2 at same time by blocking antibodies greatly alleviated arthritis. We also found that neither IL-17 nor CXCR2 alone is sufficient to trigger arthritis. Thus the results suggest that the excessive IL-17 and CXCR2 in the gut are related to the exacerbation of arthritis in a manner by which the inflammatory signals can be connected between the gut and the joints.

Features of impact of hyperferritinemia in combination with hyperuricemia on the course of gout.

The purpose of the study is to find out the frequency of development of hyperfer­ritinemia in combination with hyperuricemia in patients with gout, to assess their pathogenetic significance and to outline their role in the development of joint syndrome, to identify informative prognostic criteria. 72 patients with gout were examined. The 1st (main) group included 37 patients with gout with hyperuricemia combined with hyper­ferritinemia, whose mean age (SD) was 55.9 (10.7) years. Group 2 (comparison group) included 35 patients with gout and hyperuricemia and normal levels of ferritin (mean age - 52.8 (4.8) years). Group 3 (control) group included 20 practically healthy individuals (mean age 52.0 (2.9) years). The average level of blood uric acid was significantly dif­ferent (p=0.0254) in the main group and the comparison group and amounted to 464.5 (122.5) μmol/L and 403.8 (403.8; 403.8), respectively. The value of ferritin in the main group was significantly higher 410.2 (356.2; 415.2), p&lt;0.01) ng/mL, than in the comparison group (132.1 (20.5) ng/mL, as well as the values of the urine uric acid and C-reactive protein values (hs-CRP) (p=0.0001) 8.2 (6.0; 8.2) and 5.8 (6.1) mg/L, respectively. A direct reliable cor­relation was established (r=0.30; p&lt;0.05) between the level of blood uric acid and ferritin, the duration of gout (r=0.41; p&lt;0.05), the total number of affected joints (r=0.35; p&lt;0.03), the severity of gout (r=0.36; p&lt;0.05), as well as between the level of ferritin and the number of exacerbations of gout (r=0.44; p&lt;0.05). Hyperferritinemia in com­bination with hyperuricemia is found in 51.0% of patients with gout, significantly worsening the course of the inflammatory process Patients with gout and high levels of ferritin, unlike patients with normal levels of ferritin, have the following clinical anamnestic signs: greater number of exacerbations of gout per year, duration of gout and last outbreak of gout, exacerbation of arthritis, total number of affected joints, pain intensity during exacerbation by scale VAS. In patients with gout, the severity of the course and the form of gouty arthritis, which are determined according to imaging methods (erosion, peripheral and bone tophus, the sign of "double contour", the degree of narrowing of the joint gaps and the severity of subchondral sclerosis), have prognostic significance. The association of ferritin with blood uric acid in gout does not depend on the level of hs-CRP.

GOUT AND ARTERIAL HYPERTENSION: THERAPY PECULIARITIES

The article highlights the issues on comorbidity between gout and hypertension. Emphasis is placed on the necessity in searching for a well-balanced approach toward the treatment this type of comorbidity. Gout is a major social and economic problem in the modern society that leads to a progressive physical incapability, limitation of professional activity, thus impairing the quality of life. Arterial hypertension occurs in patients with gout in 5 - 50% of cases, and in combination with components of metabolic syndrome its prevalence rises up to 80%. As a result, the development of hypertension in patients with gout leads to a deterioration of the kidney functioning due to the combination of two pathological conditions for which the kidneys are either functioning organs or target organs. Management of arterial hypertension by general practitioner requires the searching for the most optimal approach in using metabolically neutral antihypertensives to avoid provoking medication-induced exacerbation of arthritis. In addition, the treatment of such category of patients should also provide the optimal nephroprotective effect and decrease the uric acid concentration in the serum that will contribute to the additional prevention of gout attacks.&#x0D; The aim of the study is to evaluate the nephroprotective, antihypertensive, hypolipidemic effects of the proposed combined therapy in the patients with comorbidity between gout arthritis and arterial hypertension.&#x0D; The study was conducted at the Regional Medical and Diagnostic Centre of Rheumatological Diseases, M.V. Sklifosovskyi Poltava Regional Clinical Hospital, which is the clinical base of the Department of Family Medicine and Therapy, Ukrainian Medical Stomatological Academy. 60 patients with mean age of 54.2 ± 8.6 years were enrolled to the study. The patients suffering from gout arthritis and comorbid hypertension formed the main group. The control group consisted of 60 patients matched by age, demographic and clinical parameters.&#x0D; Following the 12-month treatment period, we have registered clinical effects of the combination therapy proposed in patients with gout and comorbid hypertension. We observed a decrease in blood lipids values in the study groups: total cholesterol decreased by 16.0% in the main group and by 8.0% in the control group, high-density lipoproteins – by 5.6% in the main group and by 6.4% in the control group, low density lipoproteins – by 3.3% in the main group and by 3.4% in the control group, triglycerides – by 22.2% in the main group and 12.3% in the control group.&#x0D; We observed statistically significant improvement in the glomerular filtration rate in the main group (6.4% of cases vs. 1.3% in the control group). The blood creatinine in the both study groups decreased significantly. The uric acid blood concentration decreased by 32.6% in the main group compared to 24.6% in the control group. During the six month period of the therapy the necessity for non-steroidal anti-inflammatory drugs cut down by 58% in the study group vs. 37% in the control group.&#x0D; Conclusions. After 12 month period of therapy proposed, the patients with gout and comorbid hypertension demonstrated clinically confirmed improvement in both study groups (87.7% of patients in the main group vs. 48.6% in the control group). The efficacy of the proposed treatment was assessed by physicians up to 87%, vs. 88% efficacy assessed by the patients in the main group.

Experience with canakinumab in a patient with gout and IgA nephropathy

The paper discusses the results of clinically using the interleukin-1_ inhibitor canakinumab in a patient with chronic tophaceous gout, IgA nephropathy, and chronic kidney disease with resistance to traditional anti-inflammatory drugs (colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), and high-dose glucocorticoids) and a history of failed urate-lowering therapy. It demonstrates the possibility of safely using subcutaneous canakinumab 150 mg that is superior to therapy with high-dose prednisone (40-80 mg/day) and NSAIDs. Canakinumab has also reduced the risk of exacerbations of arthritis when choosing urate-lowering therapy.

Synergetic effect of an autoantigen CII and a mycoplasma superantigen on the onset and development of autoimmune arthritis in mice

Abstract An infection can amplify an autoimmune disease by either exacerbating an ongoing disorder, including a relapse, or by leading to chronic progressive disease. We have been studying a mouse autoimmune arthritis induced by M. arthriditis. M. arthritidis produces a potent superantigen (SAg) MAM, which is shown to be partially responsible for the chronic autoimmune arthritis. Although the MAM clearly plays a role in disease induced by live M. arthritidis, MAM alone does not induce overt disease. It does alter the immune system rendering mice more susceptible to disease that caused by other autoimmune agents such as type II collagen (CII). A key question however is how do CII and MAM act together in the host to initiate inflammation and then an autoimmune arthritis? MAM was injected into mice convalescing from CIA or mice suboptimally immunized with CII. In contrast to controls, MAM caused an exacerbation of arthritis in mice that were recovering from CIA. MAM also triggered arthritis onset in mice that had been immunized with CII up to 71 days previously. Injection of MAM during the onset phase of CIA also triggered and enhanced the severity of arthritis in mice given low doses of CII. We also tested the CII-specific immune responses in mice injected with CII alone and also to the mixtures of the CII and MAM. The T cell profile analysis demonstrated that MAM significantly promoted IL-17 and IFNg following exposure to CII in vivo. Of particular interest was that MAM-enhanced IL-17 can stimulate synoviocytes to release a spectrum of chemokines, CXCL1, CXCL2, CXCL12, CCL2 and CCL5, and attracted inflammatory leukocytes. Thus, the results suggest MAM can serve as an enhancer and a trigger by activating inflammatory responses to other bioactive molecules, i.e. CII.

Radioisotope synovectomy in the treatment of patients with rheumatoid arthritis

In a number of cases, systemic therapy for rheumatoid arthritis (RA), including disease-modifying anti-rheumatic drugs, biological agents, glucocorticoids (GCs), and nonsteroidal anti-inflammatory drugs, fails to completely suppress joint inflammatory changes in the patients. Therefore, local methods are widely used in the combination therapy of RA. Intra-articular injection of hyaluronic acid (HA) is a highly local treatment modality. HA can be used as initial therapy when it is necessary to achieve rapid clinical improvement, or at a later stage of the disease, in exacerbation of arthritis. However, in some patients the effect of intra-articular HA can be short-lasting, and a favorable result can be obtained with local radiotherapy. It is based on powerful irradiation of the inflamed synovium, which is provided by intra-articular injection of radioactive isotope colloids. In Russia, RA was successfully treated with colloidal Au-198, but its production was ceased in the 1990s, and agents for radioisotope synovectomy have been long unavailable. Tungsten-188/Rhenium-188generator has been recently designed in Russia, which allows Rhenium-188 to be obtained in clinics. Preclinical trials have shown that intra-articular injection ensures good fixation of the drug in the knee joint with its insignificant accumulation in the liver and other non-target organs and tissues. Introduction of this drug into routine clinical practice can markedly improve the efficiency of treatment in patients with chronic arthritis.

Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis

Many pro-inflammatory pathways leading to arthritis have global effects on the immune system rather than only acting locally in joints. The reason behind the regional and patchy distribution of arthritis represents a longstanding paradox. Here we show that biomechanical loading acts as a decisive factor in the transition from systemic autoimmunity to joint inflammation. Distribution of inflammation and erosive disease is confined to mechano-sensitive regions with a unique microanatomy. Curiously, this pathway relies on stromal cells but not adaptive immunity. Mechano-stimulation of mesenchymal cells induces CXCL1 and CCL2 for the recruitment of classical monocytes, which can differentiate into bone-resorbing osteoclasts. Genetic ablation of CCL2 or pharmacologic targeting of its receptor CCR2 abates mechanically-induced exacerbation of arthritis, indicating that stress-induced chemokine release by mesenchymal cells and chemo-attraction of monocytes determines preferential homing of arthritis to certain hot spots. Thus, mechanical strain controls the site-specific localisation of inflammation and tissue damage in arthritis.