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Perinuclear Anti Neutrophil Cytoplasmic Antibody (p-ANCA) is a serological marker of Microscopic Polyangiitis (MPA), a vasculitis associated with lung involvement potentially mimicking Idiopathic Pulmonary Fibrosis (IPF). In this study, we evaluated the role of p-ANCA in predicting clinical evolution and prognosis in a cohort of IPF patients. In this observational, retrospective, case–control study, we compared 18 patients with an IPF diagnosis and p-ANCA positivity with 36 patients with seronegative IPF, matched for age and sex. IPF patients with and without p-ANCA showed similar lung function decline during the follow-up, but IPF p-ANCA+ showed better survival. Half of IPF p-ANCA+ patients were classified as MPA for the development of renal involvement (55%) or skin signs (45%). The progression towards MPA was associated with high levels of Rheumatoid Factor (RF) at baseline. In conclusion, p-ANCA, mainly when associated with RF, could predict the evolution of Usual Interstitial Pneumonia (UIP) towards a definite vasculitis in patients, with a better prognosis compared with IPF. In this view, ANCA testing should be included in the diagnostic workup of UIP patients. [ABSTRACT FROM AUTHOR]

As the number of reports of post-acute COVID-19 musculoskeletal manifestations is rapidly rising, it is important to summarize the current available literature in order to shed light on this new and not fully understood phenomenon. Therefore, we conducted a systematic review to provide an updated picture of post-acute COVID-19 musculoskeletal manifestations of potential rheumatological interest, with a particular focus on joint pain, new onset of rheumatic musculoskeletal diseases and presence of autoantibodies related to inflammatory arthritis such as rheumatoid factor and anti-citrullinated protein antibodies. We included 54 original papers in our systematic review. The prevalence of arthralgia was found to range from 2% to 65% within a time frame varying from 4 weeks to 12 months after acute SARS-CoV-2 infection. Inflammatory arthritis was also reported with various clinical phenotypes such as symmetrical polyarthritis with RA-like pattern similar to other prototypical viral arthritis, polymyalgia-like symptoms, or acute monoarthritis and oligoarthritis of large joints resembling reactive arthritis. Moreover, high figures of post-COVID-19 patients fulfilling the classification criteria for fibromyalgia were found, ranging from 31% to 40%. Finally, the available literature about prevalence of rheumatoid factor and anti-citrullinated protein antibodies was largely inconsistent. In conclusion, manifestations of rheumatological interest such as joint pain, new-onset inflammatory arthritis and fibromyalgia are frequently reported after COVID-19, highlighting the potential role of SARS-CoV-2 as a trigger for the development of autoimmune conditions and rheumatic musculoskeletal diseases. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this perspective was to shed light on screening of uveitis among Nordic children with juvenile idiopathic arthritis (JIA). Methods: A literature search was conducted to review predictors of JIA‐uveitis and previous JIA‐uveitis screening recommendations. Results: Predictors of uveitis in JIA are younger age and positive antinuclear antibody titre at onset of JIA, specific subtypes of JIA (extended and persistent oligoarthritis, rheumatoid factor negative polyarthritis and psoriatic arthritis) and short duration of JIA. Methotrexate and monoclonal tumour necrosis factor (TNF) inhibitor treatment reduce the risk JIA‐uveitis. Conclusion: Children with all of the above risk factors should be screened frequently but if they receive TNF inhibitor or methotrexate therapy, they may be screened less frequently. Children with none of the risk factors do not benefit from long‐term screening for uveitis. A guideline for intervals and overall length of screening was prepared considering currently known risk factors for JIA‐uveitis, the Nordic population and previous guidelines. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that destroys joint cartilage and causes disability. Synovial inflammation, with angiogenesis, is an early event in the progression of the disease. Angiopoietin 2 (ANGPT2) is a cytokine with both inflammatory and angiogenic effects. Many genes can influence RA susceptibility and disease activity. The aim is to assess the relationship between ANGPT2 gene polymorphism (rs3020221) and RA. The study was a case-control study that included 212 RA patients and 238 age-and gender-matched healthy volunteers. RA disease activity was assessed using the Disease Activity Score 28 index. Erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and antibody to cyclic citrullinated peptide were measured. ANGPT2 rs3020221 C > T SNP genotyping was done using real-time polymerase chain reaction (PCR). The TT genotype was more frequently represented in RA patients than in healthy controls (18.9% and 7.1%, respectively, p < 0.001) and increased the chance of developing RA four-fold, as compared to other genotypes (OR = 4.00, 95% CI = 2.09–7.63) (p < 0.001). The CT genotype was associated with elevated levels of the inflammatory markers ESR and CRP in RA patients (p = 0.012 and 0.037, respectively) as well as the DAS28 ESR Score (p < 0.001). The presence of the T allele either under the dominant model (for genotypes CT and TT) or the recessive model (for the genotype TT) predicts RA disease. Assessment of ANGPT2 gene polymorphism is useful to predict the patients with susceptibility to RA. The presence of T allele increased the risk of developing RA disease by two folds. [ABSTRACT FROM AUTHOR]

HCV infection could have extrahepatic manifestations due to an aberrant immune response. HCV/HIV co‐infection increases such persistent immune activation. Aim of the present study is to describe the evolution of inflammatory markers used in clinical practice, mixed cryoglobulinemia (MC) and autoantibody reactivity in co‐infected individuals who achieved sustained virological response (SVR) after DAA treatment. This prospective, observational study included all HIV/HCV co‐infected subjects who started any DAA regimen from 2015 to 2020. Samples for laboratory measurements (ferritin, C reactive protein, C3 and C4 fractions, rheumatoid factor, MC, anti‐thyroglobulin Ab, anti‐thyroid peroxidase Ab, ANCA, ASMA, anti‐LKM, anti‐DNA, AMA, ANA, T CD4+ and CD8+ cell count, and CD4/CD8 ratio) were collected at baseline, after 4 weeks, at end of treatment, and at SVR12. The analysis included 129 individuals: 51.9% with a F0–F3 fibrosis and 48.1% with liver cirrhosis. Cryocrit, C3 fraction, and rheumatoid factor significantly improved at week 4; ferritin, anti‐thyroglobulin Ab, and C4 fraction at EOT; total leukocytes count at SVR12. MC positivity decreased from 72.8% to 35.8% (p <.001). T CD4+ cell slightly increased at SVR12, but with an increase also in CD8+ resulting in stable CD4/CD8 ratio. Autoantibody reactivity did not change significantly. ANA rods and rings positivity increased from 14.8% to 28.6% (p =.099): they were observed in three subjects without exposure to RBV. DAA therapy may lead to improvement in inflammatory markers and MC clearance but without significant changes in autoantibodies reactivity and CD4/CD8 ratio over a follow up of 12 weeks. [ABSTRACT FROM AUTHOR]

Objectives: To assess the differences in circulating DNA methylation levels of CXCR5 between rheumatoid arthritis (RA) and osteoarthritis (OA) and healthy controls (HC), and the correlation of methylation changes with clinical characteristics of RA patients. Methods: Peripheral blood samples were collected from 239 RA patients, 30 patients with OA, and 29 HC. Target region methylation sequencing to the promoter region of CXCR5 was achieved using MethylTarget. The methylation level of cg04537602 and methylation haplotype were compared among the three groups, and the correlation between methylation levels and clinical characteristics of RA patients was performed by Spearman's rank correlation analysis. Results: The methylation level of cg04537602 was significantly higher in the peripheral blood of RA patients compared with OA patients (p = 1.3 × 10−3) and in the HC group (p = 5.5 × 10−4). The sensitivity was enhanced when CXCR5 methylation level combined with rheumatoid factor and anti–cyclic citrullinated peptide with area under curve (AUC) of 0.982 (95% confidence interval 0.970–0.995). The methylation level of cg04537602 in RA was positively correlated with C‐reactive protein (CRP) (r =.16, p =.01), and in RA patients aged 60 years and above, cg04537602 methylation levels were positively correlated with CRP (r =.31, p = 4.7 × 10−4), tender joint count (r =.21, p =.02), visual analog scales score (r =.21, p =.02), Disease Activity Score in 28 joints (DAS28) using the CRP level DAS28‐CRP (r =.27, p = 2.1 × 10−3), and DAS28‐ESR (r =.22, p =.01). We also observed significant differences of DNA methylation haplotypes in RA patients compared with OA patients and HC, which was consistent with single‐loci‐based CpG methylation measurement. Conclusion: The methylation level of CXCR5 was significantly higher in RA patients than in OA and HC, and correlated with the level of inflammation in RA patients, our study establishes a link between CXCR5 DNA methylation and clinical features that may help in the diagnosis and disease management of RA patients. [ABSTRACT FROM AUTHOR]

Rheumatoid meningitis (RM) is a rare extra-articular manifestation of rheumatoid arthritis, usually with non-specific symptoms. In most cases, head magnetic resonance imaging (MRI) shows lamellar enhancements in leptomeninges and pachymeninges, but definitive diagnosis relies on meningeal biopsies. Here, we reported a 43-year-old RM patient without a previous history of rheumatoid arthritis. He came to seek medical assistance because of fever and headache. The head MRI showed bilateral enhancements in leptomeninges and pachymeninges, and blood tests showed that serum IgM rheumatoid factor (RF) (1010.0 IU/ml) and anti-cyclic citrullinated peptide (CCP) antibody (654.24 RU/ml) became positive with a further increase with the progression of the disease. After treatment with steroids, clinical symptoms were relieved. We also reviewed previous history, symptoms, and serum, cerebrospinal fluid and imaging findings in 15 RM cases without a history of rheumatoid arthritis published since 2010. Consistent with previous reported cases, the current case suggests importance of meningeal biopsies and increases in serum RF and anti-CCP antibody in diagnosis of RM. In addition, previous joint symptoms and chronic headaches, and leptomeningeal and pachymeningeal lesions on head MRI are also of great significance for the diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: Immunological phenomena are a minor criteria in the modified Duke Criteria for endocarditis. Given the changes in epidemiology and diagnostics, the added value of determining these phenomena in today's patients with suspected endocarditis is unknown. Methods: In a retrospective cohort study of all patients with suspected endocarditis admitted to our hospital and discussed in our endocarditis team, we determined the proportion of patients classified as definite endocarditis because of either positive IgM rheumatoid factor (IgM RF), haematuria, or Roth's spots on ophthalmology consultation. We also determined diagnostic accuracy of each of these immunological phenomena separately and combined. Results: Of 285 patients included, 138 (48%) had definite endocarditis and at least one immunological test was performed in 222 patients (78%). Elevated IgM RF was found in 22 of 126 patients tested (17%), haematuria in 78 of 196 tested (40%) and Roth's spots in six of 120 tested (5%). Eighteen of 138 patients with definite IE (13%) were classified as such because of a positive IgM RF, haematuria or Roth's spots. Haematuria had the highest sensitivity: 50.5% (95% CI 40.4–60.6) and Roth's spots the highest specificity: 98.3% (95% CI 90.8–99.9). The diagnostic accuracy results were robust in a sensitivity analysis aimed at avoiding incorporation bias. Conclusion: Among patients with a clinical suspicion of endocarditis, recommended systematic testing for immunological phenomena helped classify more patients as definite IE and is useful to confirm the diagnosis of endocarditis. [ABSTRACT FROM AUTHOR]

In this study, Raman spectroscopy was used to analyze the serum of patients with early rheumatoid arthritis (RA), and to explore the screening value of Raman spectroscopy in patients with early RA. A total of 216 patients were included in the study. Fasting venous blood was collected for routine biochemical detection, and the remaining samples were tested by serum Raman spectroscopy. Support vector machine was used for model building and training. The area under the curve (AUC) values of the model were as follows: (1) healthy group versus early RA group: 0.860, (2) healthy group versus non‐early RA group: 0.903, and (3) early RA group versus non‐early RA group: 0.918. This study shows that serum Raman spectroscopy has a good ability to screen RA and can be staged according to the course of the disease, which can provide new ideas and technical support for the diagnosis or screening of early RA. [ABSTRACT FROM AUTHOR]

Objectives: Most juvenile idiopathic arthritis (JIA) biologic disease‐modifying antirheumatic drugs (bDMARDs) trials used an open‐label run‐in period followed by randomized medication withdrawal. We used data from the run‐in period of 4 bDMARD trials to 1) delineate early response trajectory to bDMARDs and 2) identify predictors of early response. Methods: Data from the first 16 weeks of 4 bDMARD trials were used. The primary outcome was the American College of Rheumatology (ACR) Pediatric 50 (Pedi 50) response criteria: clinically significant response defined as ACR Pedi 50 or greater. The secondary outcome was the clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10) minimal disease activity state. Response transition rates and predictors were modeled using an inhomogeneous Markov multistate model. Results: Five hundred thirty‐two participants (70% receiving methotrexate, 41% prednisone) were included. By month 4, the probability of attaining ACR Pedi 50 or greater was 0.698. If ACR Pedi 50 or more was not achieved by month 1, the probability of achieving it by month 4 was 0.60. If ACR Pedi 50 or more was not achieved by month 3, the probability of achieving this by month 4 was 0.31. Age at diagnosis, disease duration, baseline rheumatoid factor, and active joint counts predicted ACR and cJADAS state transitions, adjusted for concomitant treatment. Conclusions: No response ACR Pedi 50 or more by month 1 after treatment was associated with a 0.60 probability of responding by month 4, but not responding by month 3 was associated with a 0.31 probability of response by month 4. Baseline disease duration, rheumatoid factor, and active joint counts predicted early treatment response (ACR and cJADAS10 states). [ABSTRACT FROM AUTHOR]

Objectives: Reliable biomarkers in the early stages of idiopathic arthritis (JIA) are scarce and the disease heterogeneity makes it clinically challenging to predict the risk of joint damage. Biomarkers with prognostic potential are warranted in order to individualize treatment and follow-up in JIA. The soluble urokinase plasminogen activator receptor (suPAR) has been reported as an easily measurable biomarker for prognosis and severity in several rheumatic diseases but it has never been studied in JIA. Methods: Sera from 51 well-characterized patients with JIA and 50 age- and sex-matched control subjects were collected and stored for later analysis of suPAR. Patients were carefully followed clinically over 3 years and analysis of erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (anti-CCP) were analyzed as part of clinical routine. Signs of joint erosions were evaluated by radiography. Results: Overall, the levels of suPAR did not differ significantly between JIA patients and controls but those with polyarticular involvement showed higher suPAR (p = 0.013). In addition, elevated suPAR were associated with joint erosions (p = 0.026). Two RF/anti-CCP negative individuals with erosions showed high levels of suPAR. Conclusions: We present new data on the biomarker suPAR in JIA. Our results indicate that, apart from RF and anti-CCP, analysis of suPAR could be of additional value in assessing the risk of erosions. Analysis of suPAR early could potentially guide treatment decision-making in JIA, but our observations should be confirmed in prospective studies. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a risk factor for atherosclerotic cardiovascular diseases (CVD). Given the critical roles of the immune system and inflammatory signals in the pathogenesis of CVD, we hypothesized that interrogation of CVD-related proteins using integrative genomics might provide new insights into the pathophysiology of RA. We utilized two-sample Mendelian randomization (MR) for causal inference between circulating protein levels and RA by incorporating genetic variants, followed by colocalization to characterize the causal associations. Genetic variants from three sources were obtained: those associated with 71 CVD-related proteins measured in nearly 7000 Framingham Heart Study participants, a published genome-wide association study (GWAS) of RA (19 234 cases, 61 565 controls), and GWAS of rheumatoid factor (RF) levels from the UK Biobank (n = 30 565). We identified the soluble receptor for advanced glycation end products (sRAGE), a critical inflammatory pathway protein, as putatively causal and protective for both RA (odds ratio per 1-standard deviation increment in inverse-rank normalized sRAGE level = 0.364; 95% confidence interval 0.342–0.385; P = 6.40 × 10–241) and RF levels (β [change in RF level per sRAGE increment] = − 1.318; SE = 0.434; P = 0.002). Using an integrative genomic approach, we highlight the AGER/RAGE axis as a putatively causal and promising therapeutic target for RA. [ABSTRACT FROM AUTHOR]

Objectives: Insulin like growth factor-1(IGF-1), is a modulator of immunity and inflammation, it promotes the anabolic role of growth hormone (GH) on bone and skeletal tissue. Genetic polymorphism in IGF-1 gene is reported to affect the transcriptional efficiency affecting its serum level. In this study we aim: 1) To study the presence of 192bp polymorphism of IGF-1 gene in patients of rheumatoid arthritis (RA), 2) To study the association of 192 bp polymorphism of IGF-1 gene with serum IGF-1 levels and disease severity in patients of RA. Methods: A cross-sectional study was carried out at University of Health Sciences (UHS), Lahore. Diagnosed RA cases who fulfilled the American College of Rheumatology (ACR) criteria were recruited from Fatima Memorial Hospital (FMH) and Behbud Rheumatology Clinics, Lahore during 2018-2019. Serum IGF-1 levels were determined by ELISA in blood samples of 200 RA patients and 200 healthy individuals. DNA was extracted and genetic polymorphism was determined. Results: The serum IGF-1 level in RA group was significantly lower compared to healthy group. Our study shows presence of 192bp allele of IGF-1in 77% of the studied population. Carriers of 192bp allele of IGF-1 had a significantly higher serum level of IGF-1 as compared to non-carriers in the RA patients. Rheumatoid factor (RF) positive patients had a higher number of 192bp carriers in comparison to RF negative patients. Significant difference was also seen in severity of disease between carrier and non-carriers of 192bp allele with the disease being more severe in male carriers. Conclusions: There is an association of IGF-1gene polymorphism with variation in serum IGF-1 levels and severity of RA. [ABSTRACT FROM AUTHOR]

Objectives: The development of rheumatoid arthritis (RA) has been classified into 6 phases A–F according to the present risk factors in sequence of genes, environments, autoimmunity, arthralgia and joint swelling. To clarify the ultrasound synovitis scores in at‐risk patients (phases C–E) and RA (phase F). Methods: Patients who had been experiencing hand joint symptoms for at least 6 weeks and asymptomatic patients with positive rheumatoid factor and/or anti‐cyclic citrullinated peptide antibodies were enrolled. A 40‐joint ultrasonography with semiquantitative synovitis scoring for gray scale (GS) and power Doppler (PD) images was performed. Results: A total of 139 patients were enrolled and classified into non‐RA, phase C, phase D, phase E and phase F. Total GS scores in phases C (17.4 ± 7.0), D (16.0 ± 5.4), E (18.5 ± 7.7) and F (21.8 ± 9.1) were higher than those in non‐RA (9.8 ± 4.0, P < 0.001). The total PD score in phase F (3.1 ± 4.6) was higher than that in phases C (0.2 ± 0.5), D (0.1 ± 0.4), and E (0.1 ± 0.3), as well as in non‐RA (0.0 ± 0.0, P < 0.01). A total GS score ≥14 differentiated patients at risk for RA from patients with non‐RA (area under curve [AUC] 0.82), while a total PD score ≥2 differentiated patients with RA from patients at risk for RA (AUC 0.71). Conclusion: Total GS score may differentiate patients at risk for RA from non‐RA patients, while total PD score may differentiate patients with RA from those who are at risk for RA. [ABSTRACT FROM AUTHOR]

Aim: Coronavirus disease 2019 (COVID‐19) has been proposed as triggering autoimmunity. The aim of this study was to evaluate the presence and clinical significance of autoantibodies in patients with COVID‐19. Methods: We retrospectively collected data from 245 patients who were hospitalized for COVID‐19. All patients were tested for the presence of antinuclear antibody (ANA), rheumatoid factor (RF), anti‐citrullinated peptide antibody (ACPA), and anti‐cytoplasmic neutrophil antibody (ANCA). Risk factors for death and critical COVID‐19, defined as the need for invasive mechanical ventilation or extracorporeal membrane oxygenation, were analyzed. Results: Ninety (36.7%) patients tested positive for ANA, and 51 (20.8%) patients tested positive for RF. Three patients each (1.2%) tested positive for ACPA and ANCA. RF‐positive patients had higher rates of invasive mechanical ventilation and death than RF‐negative patients (70.6% vs 28.4%, P < 0.001 and 45.1% vs 18.6%, P < 0.001, respectively). Underlying lung disease, kidney disease, heart disease, quick COVID severity index (qCSI), and lactate dehydrogenase (LDH) were associated with in‐hospital death. RF (odds ratio [OR] 7.31, 95% CI 2.50–21.37, P < 0.001), qCSI (OR 1.42, 95% CI 1.19–1.69, P < 0.001), and LDH (OR 1.004, 95% CI 1.002–1.005, P < 0.001) were associated with critical COVID‐19. Combination of RF, qCSI, and LDH showed good prognostic value (area under the curve = 0.903, P < 0.001) for critical COVID‐19. Conclusions: ANA and RF were frequently detected in COVID‐19 patients. RF could be a risk factor for critical COVID‐19. The results of this study suggest immune dysfunction contributes to the complications of COVID‐19. [ABSTRACT FROM AUTHOR]

There is little data on long-term persistence/continuation of methotrexate among Indian Rheumatoid arthritis patients. We assembled a retrospective single-center cohort consisting of RA patients (fulfilling 1987 ACR criteria) started on methotrexate as part of three academic studies (including two RCTs) from 2011 to 2016. Oral methotrexate was started at 7.5 or 15 mg per week with a target dose of 25 mg per week. Between August and December 2020, all patients were contacted (telephonically) and data were obtained from clinic files to evaluate self-reported continuation/persistence of methotrexate and reasons for discontinuation. Survival analysis using Kaplan–Meier and cox-regression were used to assess methotrexate continuation rates and factors associated with its discontinuation. This study included 317 patients with rheumatoid arthritis, with mean age and disease duration (at enrollment) of 43 years and 2 years; And positive rheumatoid factor and anti-CCP in 69 and 75%. At follow-up, 16 patients (5%) had died, whereas 103 (32.5%) had discontinued methotrexate. On Kaplan–Meier survival analysis, the mean survival (continuation) time for methotrexate was 7.3 years (95% CI 7–7.6 years). The actuarial continuation/persistence of methotrexate at 3, 5 and 9 years was 92, 81 and 51%, respectively. Among those who discontinued methotrexate, common reasons were remission of disease, symptomatic adverse effects (intolerance), perceived lack of efficacy and socioeconomic reasons. On multivariable cox-regression, symptomatic adverse effects during the first 12–24 weeks (Hazard ratio, 95% CI 1.8 (1.2–2.8)) and anti-CCP positivity (Hazard ratio, 95% CI 0.6 (0.3–1.0)) were significantly associated with hazard of discontinuation. Persistence or continuation of methotrexate was found to be good and comparable to reports in other centers world-wide. Apart from remission, the most important cause of methotrexate discontinuation was symptomatic adverse effects (intolerance). [ABSTRACT FROM AUTHOR]

Background Side effects of immune checkpoint inhibitors (ICIs), called immune-related adverse events (irAEs), closely resemble primary autoimmune or rheumatic diseases. We aimed to understand the clinical utility of rheumatic autoantibodies (rhAbs) for diagnosing irAEs. Patients and Methods Patients without pre-existing autoimmune disease (pAID) who had cancer treated with ICI(s) treatment from 1/1/2011 to 12/21/2020 and a rhAb checked were retrospectively identified. Logistic regression assessed associations between autoantibodies and irAEs, cancer outcome, and survival. Specificity, sensitivity, and positive/negative predictive values (PPV, NPV) were estimated for key rhAbs and ICI-arthritis. Kaplan-Meier analyzed objective response rate (ORR) and overall survival (OS). Results A total of 2662 patients were treated with≥1 ICIs. One hundred and thirty-five without pAID had ≥ 1 rhAb tested. Of which 70/135(52%) were female; median age at cancer diagnosis was 62 years with most common cancers: melanoma (23%) or non–small cell lung cancer (21%), 96/135 (75%) were anti-PD1/PDL1 treated. Eighty had a rhAb ordered before ICI, 96 after ICI, and 12 before and after. Eighty-two (61%) experienced an irAE, 33 (24%) with rheumatic-irAE. Pre-ICI RF showed significant association with rheumatic-irAEs (OR = 25, 95% CI, 1.52-410.86, P  = .024). Pre– and post–ICI RF yielded high specificity for ICI-arthritis (93% and 78%), as did pre– and post–ICI CCP (100% and 91%). Pre–ICI RF carried 93% NPV and pre–ICI CCP had 89% PPV for ICI-arthritis. No variables were significantly correlated with ORR. Any-type irAE, rheumatic-irAE and ICI-arthritis were all associated with better OS (P  = .000, P  = .028, P  = .019). Conclusions Pre–ICI RF was associated with higher odds of rheumatic-irAEs. IrAEs had better OS; therefore, clinical contextualization for rhAbs is critical to prevent unnecessary withholding of lifesaving ICI for fear of irAEs. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare condition with underlying polyarthritis, pitting edema, and negative rheumatoid factor. It can be associated with an underlying rheumatological condition or can present as a paraneoplastic syndrome with malignancy. We present a rare case of RS3PE associated with monoclonal gammopathy of undermined significance (MGUS). Case Report: A 62-year-old man presented in ambulatory medicine clinic with 3-month swelling of distal lower extremities that progressed to distal upper extremities. He had pain and morning stiffness in hands, left elbow, and left shoulder. Examination revealed 3+ pitting edema in bilateral hands, feet, legs, and thighs. Laboratory studies revealed normal blood counts and renal and liver functions. Erythrocyte sedimentation rate was normal; C-reactive protein was mildly elevated (0.7 mg/dL). Echocardiogram and computed tomography of chest, abdomen, and pelvis revealed mild splenomegaly (14.5 cm). Serum protein electrophoresis revealed IgG kappa monoclonal peak of 0.1 g/dL. Beta-2 microglobulin was elevated (7.4 mg/L); LDH was elevated (264 U/L). No lytic lesions were present in bones. RS3PE was diagnosed based on established diagnostic criteria. Prednisone produced significant improvement in swelling within 72 h of start; however, he required a longer duration of steroid treatment due to relapse and continued periodic MGUS surveillance. Conclusions: Our case highlights the importance of awareness of this condition in general practice to help with timely diagnosis and intervention, as this condition is steroid responsive. Also, it is important to screen for underlying autoimmune condition, hematological, and solid organ malignancies with appropriate workup. [ABSTRACT FROM AUTHOR]

Rheumatoid Arthritis (RA) is a systemic disease with many different clinical phenotypes. RA could be classified according to disease duration, seropositivity for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA), joint subtype, clinical behaviourbehavior and many other subgroups. In this review, we summarize and discuss the multifaceted aspects of RA, focusing on the relationship between autoimmunity status and clinical outcome, achievement of remission and influence on treatment response, from the 2022 International GISEA/OEG Symposium. [ABSTRACT FROM AUTHOR]

Rheumatoid factor (RF), anticyclic citrullinated peptides (Anti-CCP), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are used as disease markers for rheumatoid arthritis (RA). However, correlation of disease activity score (DAS) 28 with autoantibodies and inflammatory markers has not been studied in detail. Here, we have made an attempt to determine the association of DAS-28 with autoantibodies and inflammatory markers among the North Indian population. Further, we investigated the potential of subsets of autoantibodies in RA diagnosis. Disease activity was calculated by DAS-28-ESR calculator and levels of disease markers were estimated in serum. We noticed positive correlation between DAS-28, CRP (r=0.63, p=0.00) and ESR (r=0.72, p=0.00). Moderate and weak correlation was found with RF (r=0.41, p=0.00) and anti-CCP (r=0.25, p=0.011), respectively. Patients with positive subsets of both autoantibodies (RF+/Anti-CCP+) have shown a positive correlation with DAS-28. In our study, we found that the presence of RF and Anti-CCP in patient sera can increase the early detection rate of disease. But, for the diagnosis of disease in seronegative patients, more studies on biomarkers are required. [ABSTRACT FROM AUTHOR]

Introduction: Juvenile idiopathic arthritis (JIA) is a family of arthritic conditions that occurs in childhood. If untreated, the disease may result in poor quality of life and complications, such as long‐term joint damage, that may affect patients their entire lives. Methods: A case of a 23‐year‐old Filipino female presenting with persistent joint pain in both knees, ankles, wrists, and multiple fingers and toes since childhood was investigated. Bilateral eye pain and redness with associated headache, nausea, and vomiting, prompted consultation at the emergency room. Physical examination revealed deformity, erythema and swelling of multiple joints. Ophthalmologic exam revealed poor visual acuity of both eyes (20/100, both eyes). C‐reactive protein was elevated, and rheumatoid factor (RF) was negative. The patient underwent glaucoma drainage device (Ahmed valve) insertion on both eyes and was treated on an out‐patient basis with adalimumab, methotrexate, prednisone, folic acid, and prednisolone acetate eye drops. Conclusion: JIA is a complicated disease which begins early in life and affects patients even in adulthood. These patients may suffer from arthritis with permanent joint deformities and uveitis, among other disabilities that make daily tasks impossible, impacting patients both mentally and socially. [ABSTRACT FROM AUTHOR]

Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of systemic vasculitis with eosinophilic inflammation. However, existing classification criteria are all designed to classify EGPA among vasculitis and there is no established method distinguishing EGPA from other eosinophilic disorders. The aim of the present study was to propose a scoring system to differentiate EGPA among eosinophilic disorders. Non-supervised hierarchical clustering using Ward's method and principal component analysis (PCA) were performed for 19 clinical parameters of 58 patients with eosinophilia-related diseases at a tertiary university hospital. The newly proposed scoring system was externally validated in 40 patients at another tertiary institution. Two distinct clusters were identified, and clinical features including peripheral neuropathy, asthma, skin involvement, lung involvement, rheumatoid factor (RF) positivity, myeloperoxidase (MPO)–anti-neutrophil cytoplasmic antibody (ANCA) positivity, IgE elevation, C-reactive protein (CRP) elevation, and vasculitis pathological findings were predominantly observed in one of these clusters (p < 0.05). Ten features defining the cluster with a high rate of vasculitis were weighted by PCA to create the E-CASE (EGPA classification among systemic eosinophilia) scoring system, on a 16-point scale. Based on the distribution of scores in the primary cohort, we defined an E-CASE score ≥12 as positive, ≤ 8 as negative, and 9–11 as undeterminable. The sensitivity and specificity of the E-CASE score in the validation cohort were 93.3% and 100%, respectively. We developed and verified a novel scoring system for differentiating EGPA from other types of eosinophilic disorders. [ABSTRACT FROM AUTHOR]

To depict the spectrum of rheumatoid arthritis (RA) in Egypt in relation to other universal studies to provide broad-based characteristics to this particular population. This work included 10,364 adult RA patients from 26 specialized Egyptian rheumatology centers representing 22 major cities all over the country. The demographic and clinical features as well as therapeutic data were assessed. The mean age of the patients was 44.8 ± 11.7 years, disease duration 6.4 ± 6 years, and age at onset 38.4 ± 11.6 years; 209 (2%) were juvenile-onset. They were 8750 females and 1614 males (F:M 5.4:1). 8% were diabetic and 11.5% hypertensive. Their disease activity score (DAS28) was 4.4 ± 1.4 and health assessment questionnaire (HAQ) 0.95 ± 0.64. The rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were positive in 73.7% and 66.7% respectively. Methotrexate was the most used treatment (78%) followed by hydroxychloroquine (73.7%) and steroids (71.3%). Biologic therapy was received by 11.6% with a significantly higher frequency by males vs females (15.7% vs 10.9%, p = 0.001). The least age at onset, F:M, RF and anti-CCP positivity were present in Upper Egypt (p < 0.0001), while the highest DAS28 was reported in Canal cities and Sinai (p < 0.0001). The HAQ was significantly increased in Upper Egypt with the least disability in Canal cities and Sinai (p = 0.001). Biologic therapy intake was higher in Lower Egypt followed by the Capital (p < 0.0001). The spectrum of RA phenotype in Egypt is variable across the country with an increasing shift in the F:M ratio. The age at onset was lower than in other countries. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease, symmetrically affecting the small joints. Biomarkers are tools that can be used in the diagnosis and monitoring of RA. To systematically explore the role of the biomarkers: C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated protein (Anti-CCP), 14-3-3η protein, and the multi-biomarker disease activity (MBDA) score for the diagnosis and treatment of RA. A systematic review of the English literature using four different databases was carried out. CRP >7.1 mg/L predicted poor conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) outcome in RA. Anti-CCP, CRP ≥0.3 mg/dL, and RF predicted bone erosion and cartilage destruction. Combination of high 14-3-3η protein with RF and CRP improved the prediction of rapid erosion progression (REP). Anti-CCP was not associated with disease activity but was associated with increased radiographic damage (r = 0.46, p = 0.048). RF was not associated with joint damage but correlated with ultrasound-detected bone erosion. The 14-3-3η protein significantly correlated with inflammation, bone rremodeling, and osteoporosis in RA patients (p < 0.05). In addition, the 14-3-3η protein positively correlated with RA duration (p = 0.003), disease aactivity, and positive RF (p = 0.025) and it distinguished early from established RA. Early MBDA scores correlated with later response in disease activity after 6 and 12 weeks of treatment (p < 0.05). The MBDA score was able to differentiate between small differences in disease activity, predicted remission over 1-year pperiod, and was a strong predictor of radiographic progression of RA. The investigated biomarkers are helpful tools in clinical practice for diagnosis, monitoring of treatment, and predicting prognosis in RA patients. However, further research is still required to investigate novel biomarkers for the pre-treatment selection of potentially responsive patients before starting therapy for a precision medicine in this area. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate the frequency of cell-bound complement activation products (CB-CAPs) as a marker of complement activation in patients with suspected systemic lupus erythematosus (SLE) and the usefulness of this biomarker as a predictor of the evolution of probable SLE into SLE as classified by the American College of Rheumatology (ACR) criteria.MethodsPatients in whom SLE was suspected by lupus experts and who fulfilled 3 ACR classification criteria for SLE (probable SLE) were enrolled, along with patients with established SLE as classified by both the ACR and the Systemic Lupus International Collaborating Clinics (SLICC) criteria, patients with primary Sjögren's syndrome (SS), and patients with other rheumatic diseases. Individual CB-CAPs were measured by flow cytometry, and positivity rates were compared to those of commonly assessed biomarkers, including serum complement proteins (C3 and C4) and autoantibodies. The frequency of a positive multianalyte assay panel (MAP), which includes CB-CAPs, was also evaluated. Probable SLE cases were followed up prospectively.ResultsThe 92 patients with probable SLE were diagnosed more recently than the 53 patients with established SLE, and their use of antirheumatic medications was lower. At the enrollment visit, more patients with probable SLE were positive for CB-CAPs (28%) or MAP (40%) than had low complement levels (9%) (P = 0.0001 for each). In probable SLE, MAP scores of >0.8 at enrollment predicted fulfillment of a fourth ACR criterion within 18 months (hazard ratio 3.11, P < 0.01).ConclusionComplement activation occurs in some patients with probable SLE and can be detected with higher frequency by evaluating CB-CAPs and MAP than by assessing traditional serum complement protein levels. A MAP score above 0.8 predicts transition to classifiable SLE according to ACR criteria.

Psoriatic arthritis (PsA) is a chronic inflammatory disease in the spondyloarthropathy group with the history of psoriasis. Although some PsA findings are similar to rheumatoid arthritis (RA), rheumatoid factor negativity, some radiological and clinical findings are different in PsA. There is no spesific laboratory examination for diagnosis of PsA. On the other hand, anti-cyclic citrullinated peptide (anti-CCP) antibody positivity is a spesific finding for the diagnosis of RA. Objectives: We aimed in this study to analyse the frequency of anti-CCP positivity in PsA and the association with clinical and radiological findings. Methods: The study group is consisted of 100 PsA patients, who fulfilled the CASPAR cirteria for PsA and 100 healthy controls (HC). We filled a form for all patients, which included clinical and laboratory findings of patients. We analyzed anti-CCP antibody with micro-ELISA in the sera of patients. Results: In our study, the anti-CCP positivity was detected in 15% of PsA group and 4% of healthy controls. The difference was statistically significant (p=0,014; OR=4.24, 95% CI=1.35–13.25). Nine out of 15 anti-CCP positive patients were female, the remaining 6 were male. Thirteen patients (86,7%) had peripheral arthritis, 1 patient (6,7%) had sacroiliitis, 1 patient (6,7%) had peripheral arthritis and sacroiliitis. 42,8% of PsA patients with peripheral arthritis had asymetric olygoarthritis (6/14), 28,5% had monoarthritis (4/14) and 28,5% had symetric polyarthritis (4/14). Anti-CCP antibody positivity had no effect on the involvement of peripheral arthritis. Sacroiliitis and dactilitis were more frequent in the anti-CCP negative group. No patient with dactylitis had anti-CCP positivity (p=0.005). While, 43,5% of RF positive patients were detected anti-CCP positivity, 6,5% of RF negative patients were detected anti-CCP positivity (p=0,000). Conclusions: Our data reveals that anti-CCP positivity is more frequent in PsA compared to HC. We found no statisticall association between anti-CCP positivity and clinical or radiological findings.

Abstract Background This study evaluated the existence of anti-drug antibodies (ADAs) before and 52 weeks after switching from intravenous infliximab (IFX) to intravenous CT-P13 in patients with rheumatoid arthritis (RA). Methods We performed a prospective observational study. Twenty-eight patients (7 males and 21 females) received intravenous CT-P13 after intravenous IFX, and the clinical data were collected from medical records. Rheumatoid factor (RF) and anti-CCP antibody were examined at baseline. At baseline and 52 weeks after the start of CT-P13 treatment, the Disease Activity Score based on the 28-joint count and the levels of C-reactive protein, matrix metalloproteinase-3, and ADA, as well as the erythrocyte sedimentation rate were evaluated. ADAs were measured using an enzyme-linked immunosorbent assay kit. Results Seven (25%) and 6 (21.4%) cases were positive for ADAs at baseline and 52 weeks after, respectively. One case became newly positive for ADAs at week 52. Two of the ADA-positive cases became ADA-negative 52 weeks after. The ADA-positive group showed significantly higher RF values at baseline than the ADA-negative group (p = 0.03). No difference was observed between the ADA-positive group and the ADA-negative group regarding other clinical parameters. Conclusions The positive rate of ADAs did not increase after switching from intravenous IFX to intravenous CT-P13. Among the patients with ADAs, a high level of RF was observed at baseline.

Background: History of rheumatoid arthritis (RA) increases risk of periodontal diseases. A pro-inflammatory condition noted in periodontitis is considered a trigger for RA. Thus, periodontal treatment aimed at attenuating the pro-inflammatory state could aid in potentially reducing the risk of RA. Aims: The objective of this research was to assess the effect of periodontal therapy on rheumatoid factor, Disease Activity Score-28, anti-citrullinated protein antibody, and C-reactive protein levels in patients with chronic periodontitis (CP) and RA. Materials and methods: The sample consisted of 28 patients with CP and RA. The study was designed to be a double-blind, randomised controlled clinical study. The samples were randomly categorised to either the treatment group (n = 13) or the control group (n = 15). CP status (plaque index, bleeding on probing, probing pocket depth, clinical attachment loss), clinical rheumatologic status (Disease Activity Score), and biochemical status (C-reactive protein, anti-citrullinated protein antibody, and rheumatoid factor) were assessed at baseline and at follow-up at 8 to 12 weeks. Results: The treatment group showed a highly statistically significant reduction in bleeding on probing (P < .005), probing pocket depth (P < .001), plaque index (P < .001), and C-reactive protein (P < .001); a gain in the clinical attachment loss (P < .001) and an improvement in Disease Activity Score-28 (P = .001) were observed at reassessment following nonsurgical periodontal treatment as compared to the control group. However, blood serum anti-citrullinated protein antibody (P = .002) and rheumatoid factor levels (P = .351) were found to increase from baseline to 8 to 12 weeks following subgingival scaling and root planing. Conclusions: Reduction of inflammation in the periodontium by nonsurgical periodontal therapy did not reduce anti-citrullinated protein antibody and rheumatoid factor levels. However, it has shown improvement in periodontal conditions, and remarkable changes were observed in the clinical Disease Activity Score and C-reactive protein levels of individuals with RA.

Abstract Objective To investigate the correlation between the triglyceride-glucose (TyG) index and rheumatoid factor levels and the existence of cardiovascular disease in patients in the rheumatoid arthritis population and to analyze their potential value in predicting the risk of cardiovascular disease. Methods Patients with rheumatoid arthritis treated by the Traditional Chinese Medicine Department of Rheumatism of the China-Japan Friendship Hospital from 2019–01 to 2021–12 were included in this retrospective study. Regression analysis was performed with multifactor-corrected multimodal logistic models to observe the correlation between the TyG index and rheumatoid factor and cardiovascular disease risk, construct predictive models and assess the potential predictive value of the variables on cardiovascular disease risk with receiver operating characteristic curves. The results were further corrected by sensitivity analysis and trend tests. Results A total of 418 patients with rheumatoid arthritis were included in the study. In the rheumatoid arthritis population, high rheumatoid factor (OR = 1.002, 95% CI = 1.001–1.002, P

Objective. Inflammation in rheumatoid arthritis (RA) leads to the development of local and generalized bone loss. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACCP) are believed to play a negative role in the radiological progression of RA. The use of such antiresorptive therapy as denosumab – monoclonal antibodies to RANKL (receptor activator of nuclear factor kappa-B ligand), reduces the activity of osteoclasts, increases bone mineral density (BMD), and also potentially affects the erosive process at RA. The aim of the study is to evaluate the effect of denosumab therapy on BMD and erosion count in patients with RA and osteoporosis (OP) in consideration of the positivity in the RF and ACCP in serum and the baseline RA activity. Materials and methods. The 12-month prospective study of the efficacy of denosumab therapy (60 mg subcutaneously every 6 months) in patients with RA and OP included 66 postmenopausal women; age – 59.4±7.5 years, duration of RA – 17.8±10.6 years, RF-positive – 47 (72%) patients, ACCP-positive – 48 (74%) patients. At baseline and after 12 months, dual-energy X-ray absorptiometry was performed with an assessment of BMD in the lumbar spine (L1– L4), proximal femur (hip neck and total hip), distal forearm; X-ray of the hands and distal parts of the feet in direct projection, followed by assessment of erosive-destructive changes according to the Sharp/van der Heijde method. Results. A significant increase in BMD was established in all studied sites of the skeleton despite the positivity of the RF and ACCP (for the hip neck p=0.05), while a significant increase in BMD in the RF- and ACCP-negative group was detected only in L1–L4 site. The progression of the increase in erosion count was noted in the RF- and ACCP-positive group while in the RF- and ACCP-negative group this indicator did not change. Regardless of the baseline activity of RA (by DAS28 (Disease Activity Score 28)) the BMD of most parts of the skeleton were stabilized. In patients with moderate RA activity, BMD increased significantly in L1–L4 in both groups: RF- and ACCP-positive and -negative , as well as in the total hip – in RF- and ACCP-positive group. The dynamics of the erosion count in RA patients did not depend on the baseline degree of DAS28 activity, no significant changes were detected in the analyzed groups. Conclusions. RF and ACCP positivity in serum in patients with RA and OP treated with denosumab did not have a negative effect on the dynamics of BMD, while the number of erosions increased. The baseline RA activity level did not affect the dynamics of the erosion count and the dynamics of BMD in most subgroups – BMD levels have been increased or stabilized.

Abstract Background Rheumatoid arthritis, metabolic syndrome (MS) and cardiovascular disease (CVD) are mutually connected. We aim to investigate the association between rheumatoid factor (RF) and MS in general population, explore the potential value of RF for assessment of metabolic status, and further provide a reference to the establishment of CVD primary prevention for this population. Methods We assessed the health check-up subjects, accordance with the inclusive criteria, from 1 January 2015 to 31 October 2021 in a large refereed general hospital, in this retrospective study. Subjects were categorized into four groups according to their levels of RF. Multivariate logistic regression models along with the Odds ratio (OR) and Confidence interval (CI) values were used to measure the association between RF and MS. Results A total of 13,690 subjects were analyzed. Prevalence of MS increased with RF level (P for trend

Crinum pedunculatum (R.Br) has been used by traditional medicine practitioners in Ghana for the topical management of inflammation and associated disorders. This study investigated the anti-arthritic activity of the methanol, ethanol and ethyl acetate extract of the bulbs of Crinum pedunculatum using Sprague Dawley rats. The anti-arthritic activity of Crinum pedunculatum at various doses (100, 200 and 400 mg/kg) was evaluated using Complete Freund’s Adjuvant (CFA) in rat model. After successful induction of the arthritis, the paw oedema, hematological parameters, pro-inflammatory cytokines and arthritis marker were assessed. Also, the radiological and histopathological evaluations were also performed. There was a significant inhibition (P