Prognostic models of drug-induced neutralizing antibody formation in patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis treated with TNF-α blockersockers.

AIM: This study aimed to construct prognostic mathematical models utilizing multifactorial regression analysis to assess the risk of developing drug-induced neutralizing antibodies in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis treated with tumor necrosis factor alpha blockers.

Coexistence of ankylosing spondylitis and Behçet's disease: Successful treatment with upadacitinib.

BACKGROUND: Ankylosing spondylitis (AS) and Behçet's disease (BD) are distinct inflammatory disorders, but their coexistence is a rare clinical entity. This case sheds light on managing this complex scenario with Janus kinase (JAK) inhibitors. CASE PRESENTATION: A 42-year-old woman presented with a decade-long history of lower back pain, nocturnal spinal discomfort, recurrent eye issues, oral and genital ulcers, hearing loss, pus formation in the left eye, and abdominal pain. Multidisciplinary consultations and diagnostic tests confirmed AS (HLA-B27 positivity and sacroiliitis) and BD (HLA-B51). Elevated acute-phase markers were observed. CONCLUSION: This case fulfills diagnostic criteria for both AS and BD, emphasizing their coexistence. Notably, treatment with upadacitinib exhibited promising efficacy, underscoring its potential as a therapeutic option in patients with contraindications for conventional treatments. Our findings illuminate the intricate management of patients presenting with these two diverse systemic conditions and advocate for further exploration of JAK inhibitors in similar cases.

Diagnostic and prognostic role of serum interleukin-6 and carotid ultrasonography to detect subclinical atherosclerosis in patients with RA and ANCA-associated vasculitis.

ANCA-associated vasculitis (AAV) can affect multiple organs with severe life-threatening manifestations. Disease monitoring is difficult due to a lack of defined biomarkers. We aimed to assess the diagnostic role of serum interleukin-6 and vascular ultrasonography in AAV and subclinical atherosclerosis. The study included 20 AAV patients and two control groups of 34 patients with rheumatoid arthritis (RA) and 35 healthy controls. The levels of Il-6, carotid intima-media thickness test (CIMT), atherosclerotic plaque, and degree of stenosis were investigated. A GRACE-risk score was calculated for AAV and RA patients. The AAV patients had elevated levels of IL-6 (115 ± 23.96) compared to the RA patients (91.25 ± 42.63) and the healthy controls (15.65 ± 3.30), p < 0.001. IL-6 showed a diagnostic accuracy of 73% in distinguishing AAV from RA patients (AUC = 0.730; 95% CI 0.591 to 0834). In the AAV group, CIMT was 1.09, above the upper reference value of 0.90, p < 0.001. The AAV patients had a higher median GRACE risk score, and 60% of them had a high risk of cardiovascular events as compared to 35% of the RA patients. Sonography of extracranial vessels and serum levels of IL-6 can be used in daily clinical practice to diagnose and monitor patients with AAV.

Comprehensive Exploration of Antinuclear Antibodies (ANAs): Unveiling Clinical Significance, Associations with Cancer, and the Nuances of Differential Diagnosis in Positive ANA Patients.

This comprehensive review delves into the complex realm of antinuclear antibodies (ANAs), expanding beyond their traditional involvement in autoimmune rheumatic disorders. By digging into historical changes, diagnostic complexity, and clinical significance, the debate reveals the shifting relationships between ANAs, particularly with cancer. Specialized studies provide practical insights on ANA testing processes, standardization, and upcoming challenges. Examining prevalence trends in the United States provides a time dimension to ANA dynamics, linking autoimmune and oncological considerations. The debate delves into the complexity of lupus erythematosus, emphasizing ANAs' diverse presentations and their potential as flexible diagnostic and prognostic indicators. The complex relationship between ANAs and cancer is highlighted, demonstrating their potential as early markers or indicators of malignancies. Looking ahead, this synthesis anticipates advances in personalized medicine and collaborative research, putting ANAs at the forefront of advanced diagnostics and treatments for autoimmune disorders and cancer. This synthesis envisions a future for ANA research in which these antibodies play a critical role in promoting personalized treatment, enhancing diagnostics, and fostering collaborative initiatives that cross traditional boundaries. As ANAs grow more prominent at the junction of autoimmune illnesses and cancer, this synthesis lays the path for further research and novel advances in understanding, diagnosing, and treating complicated medical conditions.

Examining the Safety Profile of Janus Kinase (JAK) Inhibitors in the Management of Immune-Mediated Diseases: A Comprehensive Review.

Janus kinase (JAK) inhibitors have heralded a paradigm shift in the management of immune-mediated diseases. While their efficacy is well-established, the safety concerns associated with these agents, particularly regarding thromboembolic events (TE), remain a focus of extensive research and clinical scrutiny. This comprehensive literature review embarks on an exploration of the multifaceted landscape of JAK inhibitors, providing insights into their safety profiles across diverse immune-mediated diseases. The introduction highlights the transformative influence of JAK inhibitors in the treatment of immune-mediated diseases. Historically, the therapeutic arsenal for these conditions included corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biologics. The advent of JAK inhibitors has revolutionized this landscape, although concerns about their safety persist. This review strives to comprehensively evaluate their safety, amalgamating knowledge from multiple studies and trials. The subsequent sections delve into the safety of specific JAK inhibitors in the context of rheumatoid arthritis, inflammatory bowel diseases, and dermatologic conditions and their associations with venous thromboembolism. The evolving understanding of TE risk, particularly the intricate relationship between these agents and immune-mediated diseases, is meticulously unravelled. The concluding remarks underscore the dynamic nature of TE risk assessment with regard to immune-mediated diseases involving JAK inhibitors. It underscores that risk assessment is multifactorial, influenced not only by the choice of JAK inhibitor but also by the nuances of the underlying immune-mediated disease and the unique patient characteristics. This review offers a holistic perspective on TE risks associated with JAK inhibitors and contributes to the ongoing dialogue regarding their safety in the realm of immune-mediated diseases.

Celebrating Versatility: Febuxostat's Multifaceted Therapeutic Application.

Febuxostat, initially developed as a xanthine oxidase inhibitor to address hyperuricemia in gout patients, has evolved into a versatile therapeutic agent with multifaceted applications. This review provides a comprehensive overview of febuxostat's mechanism of action, its effectiveness in gout management, its cardiovascular safety profile, renal and hepatic effects, musculoskeletal applications, safety considerations, and emerging research prospects. Febuxostat's primary mechanism involves selective inhibition of xanthine oxidase, resulting in reduced uric acid production. Its pharmacokinetics require personalized dosing strategies based on individual characteristics. In gout management, febuxostat offers a compelling alternative, effectively lowering uric acid levels, relieving symptoms, and supporting long-term control, especially for patients intolerant to allopurinol. Recent studies have demonstrated its cardiovascular safety, and it exhibits minimal hepatotoxicity, making it suitable for those with liver comorbidities. Febuxostat's potential nephroprotective effects and kidney stone prevention properties are noteworthy, particularly for gout patients with renal concerns. Beyond gout, its anti-inflammatory properties hint at applications in musculoskeletal conditions and a broader spectrum of clinical contexts, including metabolic syndrome. Emerging research explores febuxostat's roles in cardiovascular health, neurological disorders, rheumatoid arthritis, and cancer therapy, driven by its anti-inflammatory and antioxidative properties. Future directions include personalized medicine, combination therapies, mechanistic insights, and ongoing long-term safety monitoring, collectively illuminating the promising landscape of febuxostat's multifaceted therapeutic potential.

Exploring the Novel Dimension of Immune Interactions in Pain: JAK Inhibitors' Pleiotropic Potential.

This review explores the link between immune interactions and chronic pain, offering new perspectives on treatment. It focuses on Janus kinase (JAK) inhibitors' potential in pain management. Immune cells' communication with neurons shapes neuroinflammatory responses, and JAK inhibitors' effects on pain pathways are discussed, including cytokine suppression and microglial modulation. This review integrates studies from rheumatoid arthritis (RA) pain and central sensitization to highlight connections between immune interactions and pain. Studies on RA joint pain reveal the shift from cytokines to sensitization. Neurobiological investigations into central sensitization uncover shared pathways in chronic pain. Clinical evidence supports JAK inhibitors' efficacy on pain-related outcomes and their effects on neurons and immune cells. Challenges and future directions are outlined, including interdisciplinary collaboration and dosing optimization. Overall, this review highlights JAK inhibitors' potential to target immune-mediated pain pathways, underscoring the need for more research on immune-pain connections.

Serum and Synovial Levels of Cathepsin G and Cathepsin K in Patients with Psoriatic Arthritis and Their Correlation with Disease Activity Indices.

This retrospective case-control study examined the relationship between the serum and synovial levels of cathepsin G (CatG) and cathepsin K (CatK) in patients with psoriatic arthritis (PsA) and their association with disease activity. Methods: This case-control study involved 156 PsA patients, 50 patients with gonarthrosis (GoA), and 30 healthy controls. The target parameters were measured using enzyme-linked immunosorbent assay (ELISA) kits. The serum levels of CatG and CatK were found to be significantly higher in PsA patients compared to both control groups (p < 0.001). Moreover, they could distinguish PsA patients from healthy controls with 100% accuracy. Synovial fluid CatG and CatK were positively associated with the following indicators of disease activity: the VAS (rs = 0.362, rs = 0.391); the DAPSA (rs = 0.191, rs = 0.182); and the mCPDAI (rs = 0.378, rs = 0.313). Our results suggest that serum and synovial fluid CatG and CatK levels could serve as biomarkers for PsA. In PsA patients with synovial fluid crystals, elevated synovial CatG levels demonstrated a sensitivity of 89.54% and a specificity of 86.00% in distinguishing them from PsA patients without crystals. Similarly, elevated synovial CatK levels had a sensitivity of 93.67% and a specificity of 94.34% for distinguishing PsA patients with synovial fluid crystals from those without. Furthermore, the synovial fluid levels of both CatG and CatK showed positive associations with key indicators of disease activity, including the visual analog scale (VAS) (rs = 0.362, rs = 0.391), the disease activity in psoriatic arthritis (DAPSA) (rs = 0.191, rs = 0.182), and the modified composite psoriatic disease activity index (mCPDAI) (rs = 0.378, rs = 0.313). In conclusion, our findings suggest that the serum and synovial fluid levels of CatG and CatK hold promise as potential biomarkers for assessing disease activity in psoriatic arthritis.

Accessibility to and awareness of rheumatology care provided by a nurse - a pilot study.

INTRODUCTION: Good medical care depends both on the access to specialists and awareness of patients and healthcare professionals. AIM: The purpose of this study was to assess the accessibility to rheumatology outpatient care and the awareness of patients with inflammatory joint diseases with regard to the types of sources and preferences of sources for obtaining information related to their disease and treatment, as well as to establish the extent to which this information is useful to patients. MATERIALS AND METHODS: A pilot, cross-sectional, single center, anonymous study was conducted among adult patients with inflammatory joint diseases who were monitored in an outpatient rheumatology room at St George Diagnostic and Consultative Center in Plovdiv. A total of 56 patients were monitored. The questionnaire contained 56 questions, divided into 5 main groups: 1. questions about the disease, 2. questions about the sociodemographic profile of the patients, 3. questions about accessibility to specialized healthcare, 4. questions about the role of the nurse in the training of patients with inflammatory joint disease, and 5. questions evaluating the attitude to the monitoring medical team. The data were analyzed with IBM SPSS V.26, at a statistical significance level of p<0.05 for all analyses. RESULTS: Women predominated among the patients under observation (37, 66%), as well as patients in the age group of 50-79 years (46, 82%). Twenty-four (42.9%) were the patients attending the consulting room twice a year. On-the-spot booking in the consulting room was preferred mainly among patients who lived within 50 km (3/16, 19%), while the rest of the patients preferred booking appointments by phone. Forty-five (80%) patients of the total number of patients used subcutaneous biological agents. Among them, the patients whose first application was performed by a nurse in a rheumatology room predominated (44 patients, 96%). All respondents (56, 100%) indicated that they had received self-injection training from a healthcare professional. CONCLUSION: Patients with inflammatory joint diseases need information to help them manage issues related to their disease and treatment, as well as cope with their physical and psychological needs. Our study shows that patients most commonly use a combination of information sources - they get information from a doctor or from a healthcare professional, i.e. a nurse. We highlighted in the study the crucial role of nurses in improving the access of patients to specialized rheumatology care and satisfying patients' information needs.

Prognostic models for the development of diffuse idiopathic skeletal hyperostosis.

INTRODUCTION: Diffuse idiopathic skeletal hyperostosis (DISH) is a common worldwide disease in adults over 50 years of age. The clinical diagnosis at the beginning of the disease is very difficult, even impossible, without typical symptoms and image changes. Mathematical models for searching risk factors include analysing medical history data, comorbidities, biochemical and instrumental results.

Assessing acceptability and identifying barriers and facilitators to implementation of the EULAR recommendations for patient education in inflammatory arthritis: a mixed-methods study with rheumatology professionals in 23 European and Asian countries.

OBJECTIVES: To disseminate and assess the level of acceptability and applicability of the European Alliance of Associations for Rheumatology (EULAR) recommendations for patient education among professionals in rheumatology across Europe and three Asian countries and identify potential barriers and facilitators to their application. METHODS: A parallel convergent mixed-methods design with an inductive approach was used. A web-based survey, available in 20 different languages, was distributed to health professionals by non-probability sampling. The level of agreement and applicability of each recommendation was assessed by (0-10) rating scales. Barriers and facilitators to implementation were assessed using free-text responses. Quantitative data were analysed descriptively and qualitative data by content analysis and presented in 16 categories supported by quotes. RESULTS: A total of 1159 completed the survey; 852 (73.5%) were women. Most of the professionals were nurses (n=487), rheumatologists (n=320), physiotherapists (n=158). For all recommendations, the level of agreement was high but applicability was lower. The four most common barriers to application were lack of time, lack of training in how to provide patient education, not having enough staff to perform this task and lack of evaluation tools. The most common facilitators were tailoring patient education to individual patients, using group education, linking patient education with diagnosis and treatment and inviting patients to provide feedback on patient education delivery. CONCLUSIONS: This project has disseminated the EULAR recommendations for patient education to health professionals across 23 countries. Potential barriers to their application were identified and some are amenable to change, namely training patient education providers and developing evaluation tools.

Assessment of serum and synovial fluid MMP-3 and MPO as biomarkers for psoriatic arthritis and their relation to disease activity indices.

Research on biomarkers for the diagnosis and monitoring of psoriatic arthritis (PsA) is ongoing. The purpose of this study was to assess the potential of serum and synovial fluid matrix metalloproteinase-3 (MMP-3) and myeloperoxidase (MPO) as biomarkers for PsA and their relation to disease activity indices. This case-control study involved 156 psoriatic arthritis patients, 50 gonarthrosis patients, and 30 healthy controls. The target parameters were measured with the enzyme-linked immunosorbent assay (ELISA) kits. Serum MMP-3 and MPO levels were elevated in the PsA patients in comparison to the two control groups (p < 0.001) and distinguished PsA from GoA patients and healthy controls with 100% accuracy. Synovial MMP-3 discriminated PsA from GoA patients irrespective of the presence of crystals (AUC = 1.00). PsA patients with crystals in the synovial fluid had elevated synovial MPO (p < 0.001) and were distinguished from PsA patients without crystals with accuracy of 88.50% and from GoA patients with accuracy of 88.30%. Synovial fluid MPO was positively associated with the following indicators of disease activity: VAS (rs = 0.396); DAPSA (rs = 0.365); mCPDAI (rs = 0.323). Synovial MMP-3 showed a weaker positive association with DAPSA (rs = 0.202) and mCPDAI (rs = 0.223). Our results suggest that serum MMP-3 and MPO could serve as biomarkers for PsA. Synovial fluid MMP-3 showed a potential as a biomarker for PsA versus GoA. Synovial MPO could be utilized as a marker for the presence of crystals in PsA patients.

Assessment of TNF-α expression in unstable atherosclerotic plaques, serum IL-6 and TNF-α levels in patients with acute coronary syndrome and rheumatoid arthritis.

The role of inflammatory cytokines is well researched in acute coronary syndrome (ACS) and rheumatoid arthritis (RA), but not in the presence of both conditions. This study aimed to compare TNF-α expression, serum TNF-α, IL-6, and hs-CRP in ACS patients with RA (n = 46) with ACS patients without RA (n = 49) and healthy controls (n = 50). TNF-α expression was assessed from coronary artery samples, taken during coronary artery bypass surgery. Serum levels TNF-α, IL-6, and hs-CRP were measured 24 and 48 h after cardiac surgery. Stronger TNF-α expression was observed in the ACS patients with RA versus the ACS patients without RA, p = 0.001. Serum TNF-α, IL-6, and hs-CRP at the 24th h were significantly elevated in both patient groups and distinguished them from the healthy controls with accuracy ranging from 80 to 99%. At the 48th h, serum TNF-α and IL-6 in the ACS group without RA decreased to those of the healthy controls but remained high in the group with RA. ACS cases with RA could be correctly identified from the levels of IL-6 (AUC = 0.885, 95% CI 0.791 to 0.938) and TNF-α (AUC = 0.852, 95%CI 0.720 to 0.922). Our results suggest that the presence of RA in ACS cases is likely to provoke stronger TNF-α expression on atherosclerotic plaques, aggravate the pro-inflammatory response, and sustain it even after the cardiac stress is lowered. In ACS cases with RA, long-term monitoring and control of TNF-α and IL-6 levels can be a useful preventive strategy.

Assessment of Crystals in the Synovial Fluid of Psoriatic Arthritis Patients in Relation to Disease Activity.

Background: This study examines the relationship between the presence of crystals in the synovial fluid of patients with psoriatic arthritis (PsA) and disease activity. Methods: The synovial fluid of 156 PsA patients was analyzed and compared to 50 patients with gonarthrosis (GoA). The Leica DM4500P polarization microscope was used for crystal detection. Results: The presence of crystals was observed in 23.71% of PsA patients and none of the GoA patients, p < 0.001. Monosodium urate crystals (67.58%) and calcium pyrophosphate crystals (21.62%) were prevalent. The presence of crystals in the synovial fluid of PsA patients was associated with high disease activity according to the Composite Psoriatic Disease Activity Index (OR = 18.75, 95%; CI: 7.13 to 49.25) and the Disease Activity for Psoriatic Arthritis (OR = 15.96, 95%; CI: 5.76 to 44.23), with severe disability according to the Health Assessment Questionnaire Disability Index (OR = 13.60, 95%; CI: 5.09 to 36.31), and with severe pain on the Visual Analog Scale (OR = 157.25, 95%; CI: 39.50 to 625.94). Conclusion: Our results suggest that synovial fluid examination should be included in the treatment pathway for PsA patients with active disease, to aid in determining whether urate-lowering therapy is required.

Capillaroscopy and Immunological Profile in Systemic Sclerosis.

Introduction: Data on the associations between capillaroscopic changes and diagnostic systemic-sclerosis (SSc)-related antibodies are scarce. Presence of such correlation would improve current knowledge about the disease's pathogenesis by revealing the mechanisms of microangiopathy. The microvascular pathology of SSc is a hallmark of the disease, and immunological abnormalities probably contribute to its development. Patients and methods: 19 patients with definite diagnosis of SSc were included in the current pilot study; 16 had limited and 3 had diffuse cutaneous involvement; their mean age was 51.56 ± 15.07 years. All patients exhibited symptoms of Raynaud's phenomenon of the fingers. A "scleroderma" type capillaroscopic pattern was classified according to the staging suggested by Cutolo et al. (2000): "early", "active" or "late" phase. In the presence of different degrees of capillaroscopic changes in different fingers, the most-advanced microvascular pathology was chosen for classification. In cases without capillaroscopic features of microangiopathy, the findings were categorized as normal or nonspecific (dilated, tortuous capillaries, and/or hemorrhages). Indirect immunofluorescence on HEp-2 cells was performed as the gold-standard screening method for the detection of antinuclear autoantibodies (ANA), and determination of the immunofluorescent staining pattern (anti-cell pattern) was in accordance with the International Consensus on ANA Patterns. Scleroderma-associated autoantibodies in the patients' serum were assessed using line immunoblot assay for detection of autoantibodies to 13 scleroderma-associated autoantigens: Scl-70, CENP A, CENP B, RP11/RNAP-III, RP155/RNAP-III, fibrillarin, NOR-90, Th/To, PM-Scl100, PM-Scl75, Ku, PDGFR, and Ro-52. Results: In 73.7% (n = 14) of the examined patients, "scleroderma" type capillaroscopic changes were found, and in 26.3% (n = 5), capillaroscopic features of microangiopathy were absent (nonspecific changes, n = 3; normal findings, n = 2). In SSc patients with positive anti-Scl-70 (n = 7) antibodies, significantly lower mean capillary density was observed along with a higher frequency of "active" and "late" phase capillaroscopic changes as compared to the anti-Scl-70-negative patients (p < 0.05). Anti-RNAP III−155 positive patients (n = 4) had significantly higher mean capillary density than anti-RNAP III−155 negative patients (n = 15). In three of the anti-RNAP III−155-positive cases, capillaroscopic features of microangiopathy were not detected, and in one case there was an "early" phase "scleroderma" pattern. Conclusion: In the current pilot study, the association between more advanced capillaroscopic changes and the presence of anti-Scl-70 autoantibodies was confirmed. As a novel observation, positive anti-RNAP III−155 antibodies were found in SSc patients with or without early microangiopathy. The question of associations between microvascular changes in SSc and other SSc-related autoantibodies requires further research.

A Study of IFN-α-Induced Chemokines CCL2, CXCL10 and CCL19 in Patients with Systemic Lupus Erythematosu.

The role of IFN-α-induced chemokines CCL2, CXCL10 and CCL19 in different forms of SLE has not been studied in Bulgaria, with worldwide sources attributing varying degrees of importance. The aim of this study was to investigate the correlation between IFN-induced chemokines CCL2, CXCL10 and CCL19 and disease activity in patients with SLE over 24 months. MATERIALS AND METHODS: This study used data from 70 patients with SLE (age range 24-62 years) and a control group of 30 healthy volunteers matched for age and gender. Levels of chemokines CCL2, CXCL10 and CCL19 in lupus patients' serum were measured by ELISA. The study examined clinical and clinical laboratory indicators, as well as measures of disease activity developed for lupus patients (SLEDAI and SLICC). Statistical program SPSS, Version 26 were used for statistical data processing with p < 0.05. At 24 months of follow-up, 12 patients were with deterioration, and they had an IFN-a of 363.76 ± 9.23 versus 116.1 ± 22.1 pg/mL of those who did not worsen, CCL2 278.3 ± 5.12 versus 89.4 ± 12.8, CXCL10 234.2 ± 6.13 versus 115.23 ± 5.9 p CCL19 776.25 ± 5.1 vs. 651.34 ± 9.0 during the first visit. RESULTS: The mean values of CCL2, CXCL10 and CCL19 were higher in patients with SLE compared to healthy controls (p = 0.01). A strong significant association (p = 0.01) was found between the concentration of CCL2, CXCL10 and CCL19 and with patients' age, disease duration, SLEDAI and SLICC. CONCLUSION: CCL2, CXCL10 and CCL19 serum levels were found to correlate with patients' age and disease duration. The level of IFN-induced chemokines CCL2, CXCL10 and CCL19 has a prognostic value in terms of SLE disease activity and degree of organ damage.

Drug-neutralizing Antibodies against TNF-α blockers as Biomarkers of Therapy Effect Evaluation.

INTRODUCTION: TNF-α blocker therapy is part of the treatment with biologics used in the management of inflammatory joint diseases. In recent years, drug-induced neutralizing antibodies have been shown to have a negative effect on the course of the disease process. AIM: To investigate drug-induced neutralizing antibodies against TNF-α blocking drugs used in patients with inflammatory joint diseases and their effect on the clinical course of the disease. MATERIALS AND METHODS: The study included 121 (56.8%) patients with rheumatoid arthritis, 50 (23.5%) patients with ankylosing spondylitis, 42 (19.7%) patients with psoriatic arthritis, and 31 sex and age-matched healthy controls. The patients were monitored at 0, 6, 12, and 24 months after initiation of TNF-α blocker treatment. The demographic data, vital signs and the parameters of inflammatory activity (C-reactive protein, erythrocyte sedimentation rate, and disease activity indices) were analyzed in all patients. Drug-induced anti-TNF-α blockers antibodies (adalimumab and etanercept) were analyzed using ELISA. Statistical analysis was performed with SPSS v. 24. RESULTS: Drug-induced neutralizing antibodies against adalimumab were obtained in 11.57% of patients at 6 month, in 17.64% at 12 month, and in 24.8% at 24 month. Drug-induced neutralizing antibodies to etanercept were not demonstrated in patients followed up at 6 months, at 7.77% at 12 months, and at 9.63% at 24 months. Between the presence of neutralizing antibodies to blockers of TNF-α and indices available for disease activity, there is a strong positive correlation and Pearson Correlation = 0.701, p=0.001. Patients with poor clinical response and available antibodies against adalimumab at 12 months were 82.36% and patients treated with etanercept 71.42%. The difference between the two groups was non-significant (U = 0.527, p> 0.05). Patients with poor clinical response and available anti-adalimumab antibodies at 24 month were 75%, and in patients treated with etanercept - 87.50%, the difference between the two groups not being able to reach significance (U = 0.623, p> 0.05). CONCLUSION: Drug-induced neutralizing antibodies against TNF-α blockers (adalimumab and etanercept) have a negative effect on the course of inflammatory joint disease and can be used as reliable biomarker to assess the effect of the treatment with these drugs.

Comparison of RANKL expression, inflammatory markers, and cardiovascular risk in patients with acute coronary syndrome with and without rheumatoid arthritis.

The mechanisms responsible for increased cardiovascular risk in patients with rheumatoid arthritis (RA) involve local and systemic inflammatory processes. We aimed to compare inflammatory markers and mortality risk in patients with acute coronary syndrome (ACS) with and without RA. The study involved 95 ACS patients (46 with RA and 49 without RA) and 40 healthy controls. Serum levels of Receptor Activator of Nuclear Factor Kappa B Ligand (sRANKL), Osteoprotegerin (sOPG), high-sensitivity C-reactive protein (hs-CRP) and high-sensitivity Tropinin I (hs-TnI) were tested in all participants. Additionally, ACS patients were assessed on RANKL expression (exRANKL) on coronary arteries and mortality risk on the Global Registry of Acute Coronary Events scale (GRACE). exRANKL was established in 35 (76%) ACS patients with RA, vs. 19 (39%) patients without RA, p < 0.001. RA patients had significantly higher levels of sRANKL and sOPG at 24 h and 48 h compared to ACS patients without RA and healthy controls (sRANKL 24 h: 121.33 vs. 51.67 vs. 36.94, p = 0.019; sRANKL 48 h: 89.21 vs. 36.95 vs. 36.94, p = 0.004; sOPG 24 h: 207.71 vs. 69.39 vs. 111.91, p < 0.001; sOPG 48 h: 143.36 vs. 69.38 vs. 111.91, p < 0.001). RA patients had significantly higher RANKL:OPG ratio at 48 h (0.062 vs. 0.53 vs. 0.33, p < 0.001), hs-CRP (28.82 vs. 23.67 vs. 2.60, p < 0.001) and hs-TnI (0.90 vs. 0.76 vs. 0.012). GRACE risk score was significantly higher in RA patients vs. those without RA (140.45 vs. 125.50, p = 0.030) and correlated with exRANKL, RANKL:OPG, hs-CRP, and hs-TnI. Our results indicate that exRANKL, inflammatory markers and mortality risk are amplified in ACS patients with RA compared to ACS patients without RA.

Pathobiochemical Mechanisms Relating Iron Homeostasis with Parameters of Inflammatory Activity and Autoimmune Disorders in Rheumatoid Arthritis.

AIM: To find the correlations between the parameters of iron homeostasis, inflammatory activity and autoimmune disorders in rheumatoid arthritis (RA). MATERIALS AND METHODS: The present study included 114 patients with RA and 42 healthy controls. We determined the parameters of iron homeostasis: serum iron, total iron binding capacity (TIBC), ferritin and soluble transferrin receptor (sTfR), the parameters of inflammatory activity: C-reactive protein (CRP), interleukin-6 (IL-6) and prohepcidin, and the parameters of autoimmune disorders: rheumatoid factor (RF), anti-cyclic citrullinated peptide (antiCCP) antibodies and DAS 28. RESULTS: The levels of sTfR, CRP, IL-6 and prohepcidin were significantly higher in RA patients than those in the controls and the level of serum iron was significantly lower in RA than that in the control group. Unlike the controls, in RA, there was a significant positive correlation of sTfR with the parameters of inflammatory activity (IL-6, prohepcidin, ESR) and with the parameters of autoimmune disorders (DAS 28, RF, antiCCP). A negative correlation of serum iron with sTfR was found only in RA patients. Prohepcidin positively correlated with the parameters of inflammation (CRP, ESR) and with the parameters for evaluation of autoimmune disorders (DAS 28 and RF) in the RA group. CONCLUSION: Our study shows that the simultaneous determination of the two parameters sTfR and prohepcidin is most informative for evaluation of the changes in iron homeostasis in RA. The increase of both parameters provides information for tissue iron deficiency (assessed by the level of sTfR), caused by the inflammation when prohepcidin is expressed.

Pathobiochemical Mechanisms Relating Iron Homeostasis to Parameters of Inflammatory Activity and Autoimmune Disorders in Rheumatoid Arthritis.

AIM: To find the correlations between the parameters of iron homeostasis, inflammatory activity and autoimmune disorders in rheumatoid arthritis (RA). MATERIALS AND METHODS: The present study included 114 patients with RA and 42 healthy controls. We determined the parameters of iron homeostasis: serum iron, total iron binding capacity (TIBC), ferritin and soluble transferrin receptor (sTfR), the parameters of inflammatory activity: C-reactive protein (CRP), interleukin-6 (IL-6) and prohepcidin, and the parameters of autoimmune disorders: rheumatoid factor (RF), anti-cyclic citrullinated peptide (antiCCP) antibodies, and DAS 28. RESULTS: The levels of sTfR, CRP, IL-6 and prohepcidin were significantly higher in RA patients than those in the controls and the level of serum iron was significantly lower in RA than that in the control group. Unlike the controls, in RA, there was a significant positive correlation of sTfR with the parameters of inflammatory activity (IL-6, prohepcidin, ESR) and with the parameters of autoimmune disorders (DAS 28, RF, antiCCP). A negative correlation of serum iron with sTfR was found only in RA patients. Prohepcidin positively correlated with the parameters of inflammation (CRP, ESR) and with the parameters for evaluation of autoimmune disorders (DAS 28 and RF) in the RA group. CONCLUSION: Our study shows that the simultaneous determination of the two parameters sTfR and prohepcidin is most informative in evaluating the changes in iron homeostasis in RA. The increase of both parameters provides information for tissue iron deficiency (assessed by the level of sTfR), caused by the inflammation when prohepcidin is expressed.