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This article explores the relationship between certain HLA-DRB1 alleles and palindromic rheumatism (PR) in the Azeri population. PR is a type of arthritis characterized by temporary episodes of joint inflammation. The study reveals that specific HLA-DRB1 alleles are more prevalent in PR patients, but their presence does not significantly correlate with the development of rheumatoid arthritis or specific autoantibodies. The research suggests a potential genetic predisposition to PR in the Azeri population. Additionally, the study acknowledges the limitations of a small sample size and highlights the need for further research due to the rarity of the disease and differences between ethnic groups. [Extracted from the article]

Background Methods Results Conclusion Despite the advancements in the categorization of clinically amyopathic dermatomyositis (CADM), the classification and diagnosis of its subtypes are still challenging. The aim of our study was to describe the clinicopathological features of CADM and assess the differences between amyopathic dermatomyositis (ADM) and hypomyopathic dermatomyositis (HDM).This retrospective study included 43 patients with CADM diagnosed at our institution from 2016 to 2020. Patients were subclassed into ADM (n = 30) and HDM (n = 13) groups to assess their clinicopathological differences.All included patients had characteristic cutaneous manifestations of dermatomyositis; 67.4% had myositis‐associated auto‐antibodies, including ANA (32.6%), RNP (14.0%), anti‐Ro52 (9.3%), anti‐p155/140 (7.0%), rheumatoid factor (7.0%), anti‐NXP‐2 (4.7%), anti‐MDA5 (2.3%), and anti‐Jo‐1 (2.3%) antibodies. One patient had associated interstitial lung disease, and another patient had oral squamous cell carcinoma. The histopathological findings included mucin deposition (69.8%), telangiectasia (65.1%), lymphocytic infiltrate (48.8%), vacuolar interface dermatitis (46.5%), and epidermal atrophy (14.0%). Compared to patients with HDM, ADM patients were significantly less likely to have epidermal atrophy, 3.3% versus 38.5% (p = 0.006), and more likely to have mucin deposition, 80.0% versus 46.2% (p = 0.028).We described the clinicopathological features of CADM and highlighted the distinctions between ADM and HDM dermatopathologic findings. This information may prove helpful in diagnosing ambiguous lesions. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a complex chronic inflammatory illness that affects the entire physiology of human body. It has become one of the top causes of disability worldwide. The development and progression of RA involves a complex interplay between an individual's genetic background and various environmental factors. In order to effectively manage RA, a multidisciplinary approach is required, as this disease is complicated and its pathophysiological mechanism is not fully understood yet. In majority of arthritis patients, the presence of abnormal B cells and autoantibodies, primarily anti‐citrullinated peptide antibodies and rheumatoid factor affects the progression of RA. Therefore, drugs targeting B cells have now become a hot topic in the treatment of RA which is quite evident from the recent trends seen in the discovery of various B cell receptors (BCRs) targeting agents. Bruton's tyrosine kinase (BTK) is one of these recent targets which play a role in the upstream phase of BCR signalling. BTK is an important enzyme that regulates the survival, proliferation, activation and differentiation of B‐lineage cells by preventing BCR activation, FC‐receptor signalling and osteoclast development. Several BTK inhibitors have been found to be effective against RA during the in vitro and in vivo studies conducted using diverse animal models. This review focuses on BTK inhibition mechanism and its possible impact on immune‐mediated disease, along with the types of RA currently being investigated, preclinical and clinical studies and future prospective. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder and its characteristics include the immune system's invasion of the healthy lining of the joints and the articular structures degeneration. The IL‐21 pro‐inflammatory cytokine, and the reactive oxygen species (ROS) might have a role in the RA etiopathogenesis. The present study assessed the correlation of IL‐21 with vitamin 25(OH)D and the ROS. Methods: The study included 120 RA patients and 60 healthy group. The RA patients were categorized based on rheumatoid factor (RF) seropositivity or seronegativity and the RA severity. Chemiluminescent immunoassay and 10% hematocrit were used to check levels of vitamin 25(OH)D and ROS, respectively. ELISA was used for the detection of IL‐21 in the plasma. Results: The RA patients had a significantly reduced vitamin 25(OH)D level compared to the healthy controls. The IL‐21 and ROS were however significantly increased in the RA patients compared to the controls. Further, the seropositive RF and the high RA severity patients had significant IL‐21 and ROS increase in comparison with the seronegative RF and the low severity RA patients. Finally, IL‐21 negatively correlated with vitamin 25(OH)D, but positively correlated with the ROS. Conclusion: This is the first investigation to confirm the relationship between IL‐21 with vitamin 25(OH)D and the ROS among the RA patients. The findings indicate that vitamin 25(OH)D is reduced in the RA patients' serum. ROS and IL‐21 are also associated with increased RA severity. [ABSTRACT FROM AUTHOR]

Anti‐Golgi antibodies are uncommon antibodies that exhibit specific, polarized cytoplasmic staining on the Hep‐2 substrate. The objective of our study was to identify the clinical and laboratory features associated with anti‐Golgi antibodies. We examined 4.5 years of data from a Turkish tertiary hospital in this retrospective cohort analysis. The indirect immunofluorescence staining patterns, antinuclear antibody (ANA) titres and clinical data of all patients were obtained from the hospital record system. A total of 146,055 ANAs were detected, of which 224 patients (0.15%) exhibited anti‐Golgi antibody staining. In total, 39.4% of diagnosed patients had autoimmune diseases (AIDs). Of the AIDs, 26 (46.4%) were rheumatoid arthritis (RA). This is a very high rate and another remarkable point is that 17 (65.3%) of these patients had seronegative RA. High‐titre results (1 ≥ 1/320) were more common in patients with AID. Anti‐Ro52 was prevalent in 50% of extractable nuclear antigen (ENA)‐positive patients, making it a remarkable finding. The majority of individuals with high‐titre anti‐Golgi antibodies had AID, particularly RA. The majority of these patients also tested negative for anti‐cyclic citrullinated peptide (anti‐CCP) and rheumatoid factor (RF). Finally, high‐titre anti‐Golgi antibodies may be an important serologic marker for seronegative RA in the Turkish population. [ABSTRACT FROM AUTHOR]

Objective: To describe the epidemiology, associations, and impact of inflammatory arthritis (IA) in systemic sclerosis (SSc). Methods: Patients with SSc prospectively enrolled in the Australian Scleroderma Cohort Study were included. IA was defined clinically as the presence of synovitis on examination. Logistic regression was used to determine the associations of IA with SSc manifestations and serological parameters. Patient‐reported outcome measures were used to capture physical function and health‐related quality of life (HRQoL). Results: IA was a common SSc manifestation affecting one‐third (33.3%) of patients over a median follow‐up of 4.3 (1.7–8.4) years. Associations of IA included diffuse SSc (odds ratio [OR] 1.33, 95% confidence interval [95% CI] 1.01–1.74, P = 0.042), concurrent musculoskeletal manifestations (joint contractures and tendon friction rubs, OR 1.70, 95% CI 1.34–2.15, P < 0.001); myositis (OR 2.11, 95% CI 1.39–3.20, P < 0.001), and sicca symptoms (OR 1.57, 95% CI 1.14–2.16, P = 0.006), whereas IA was negatively associated with pulmonary arterial hypertension (OR 0.52, 95% CI 0.35–0.78, P = 0.002). Neither the presence of rheumatoid factor nor U1 small nuclear RNP were associated with IA (OR 1.13, 95% CI 0.88–1.44, P = 0.331, OR 1.46, 95% CI 0.89–2.39, P = 0.129 respectively). Positive anticyclic citrullinated protein antibodies, although at low frequency, were more common in those with IA compared with those without IA (7.5% vs 1.5%, P < 0.001). IA was associated with significantly lower HRQoL score (P < 0.001) and more physical disability than in those without IA (P < 0.001). Conclusion: IA is a common disease manifestation that is more frquently seen in diffuse disease. IA is associated with poor HRQoL and physical disability. Further research is needed into the effective management of IA in SSc. [ABSTRACT FROM AUTHOR]

Objective: The goal was to assess the degree of overlap between existing International League of Associations for Rheumatology (ILAR) and preliminary Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria for juvenile idiopathic arthritis (JIA). Methods: Participants from the Childhood Arthritis Prospective Study, a multicenter UK JIA inception cohort, were classified using the PRINTO and ILAR classification criteria into distinct categories. Systemic JIA was excluded because several classification items were not collected in this cohort. Adaptations to PRINTO criteria were required to apply to a UK health care setting, including limiting the number of blood biomarker tests required. The overlap between categories under the two systems was determined, and any differences in characteristics between groups were described. Results: A total of 1,223 children and young people with a physician's diagnosis of JIA were included. Using PRINTO criteria, the majority of the patients had "other JIA" (69.5%). There was a high degree of overlap (91%) between the PRINTO enthesitis/spondylitis‐ and ILAR enthesitis‐related JIA categories. The PRINTO rheumatoid factor (RF)–positive category was composed of 48% ILAR RF‐positive polyarthritis and 52% undifferentiated JIA. The early‐onset antinuclear antibodies–positive PRINTO category was largely composed of ILAR oligoarthritis (50%), RF‐negative polyarthritis (24%), and undifferentiated JIA (23%). A few patients were unclassified under PRINTO (n = 3) and would previously have been classified as enthesitis‐related JIA (n = 1) and undifferentiated JIA (n = 2) under ILAR. Conclusion: Under the preliminary PRINTO classification criteria for childhood arthritis, most children are not yet classified into a named category. These data can help support further delineation of the PRINTO criteria to ensure homogenous groups of children can be identified. [ABSTRACT FROM AUTHOR]

This article discusses a case report of a patient who experienced chest trauma-induced pleuritis and was subsequently diagnosed with rheumatoid arthritis (RA). The patient had a history of intermittent polyarthralgia and elevated levels of serum rheumatoid factor (RF). The pleural effusion in the patient was eosinophilic and exudative, with low complement levels and elevated adenosine deaminase (ADA) levels. The article highlights the similarities and differences between rheumatoid pleuritis and post-traumatic eosinophilic pleural effusions (EPE) or postcardiac injury syndrome (PCIS). The authors suggest that chest trauma can be a trigger for rheumatoid pleuritis, and further analysis is needed to understand the pathogenesis of lymphocytic pleurisy in more detail. [Extracted from the article]

Key Clinical Message: Although it is very uncommon, SLE may initially present with recurrent episodes of EM‐like rash. Despite the various possibilities underlying their association, prompt identification, and treatment of SLE in patients presenting with EM is important to prevent death or serious organ damage. Rowell's syndrome (RS) is an uncommon presentation of systemic lupus erythematosus (SLE) with erythema multiforme (EM)‐like lesions associated with specific serological changes, including positive rheumatoid factor (RF), speckled antinuclear antibody (ANA), positive rheumatoid factor, or anti‐La antibodies in the serum. Our case, a 41‐year‐old male, presented with features of EM. Upon investigation, we identified underlying systemic lupus erythematosus, marking a rare instance of SLE presenting for the first time as EM. Classical or true EM is precipitated by trigger factors such as infective agents like the herpes simplex virus, Mycoplasma pneumoniae, drugs like anticonvulsants, antibiotics, and non‐steroid anti‐inflammatory drugs, any underlying malignancy, or connective tissue disorders, and is not associated with any specific serological abnormalities. EM cases associated with LE lesions where an EM trigger factor is missing are considered an RS diagnostic criterion. In this case report, the importance of considering SLE in patients presenting initially with recurrent episodes of EM‐like rash is emphasized. RS should be considered, especially when there is no evidence of triggering factors. Early diagnosis and prompt treatment of SLE are crucial to preventing death and irreversible organ damage. [ABSTRACT FROM AUTHOR]

Objective: Current recommendations suggest that patients with newly presenting arthritis suspected of rheumatoid arthritis (RA) should undergo routine radiographs of hands and feet (X‐HF) as the presence of RA‐associated erosions might be of diagnostic and prognostic value. Our objective was to investigate the prevalence, diagnostic, and prognostic value of RA‐associated erosions seen on routine X‐HF in a large, recent cohort of patients with newly presenting arthritis. Methods: A retrospective cohort study was performed between 2016 and 2019 in patients with newly presenting arthritis suspected of RA. Patients were included if arthritis was present at diagnosis, rheumatoid factor and anticitrullinated protein antibodies were measured, RA was noted in the differential diagnosis, and routine X‐HF were conducted. Outcomes were the prevalence of one or more RA‐associated erosion(s), and whether diagnostic or prognostic classification were changed by erosivity. Seronegative patients, patients without acute phase reactants, and patients with longer symptom duration were analyzed as subgroups. Results: RA‐associated erosions were found in 32 of 724 patients (4.4%, 95% confidence interval [95% CI] 3.1–6.2). Erosions led to a change of diagnostic classification in two patients (0.3%, 95% CI 0.01–1.1) and changed prognostic classification in three patients (0.4%, 95% CI 0.1–1.3). Seronegative patients and patients without elevated acute phase reactants had significantly lower prevalence of erosions (χ2 9.4, P = 0.002, χ2 6.5, P = 0.01). Longer symptom duration was not associated with a different prevalence of erosions (χ2 0.4, P = 0.81). Conclusion: The recommendation of conducting routine X‐HF in patients with newly presenting arthritis suspected of RA might be reconsidered due to low prevalence of early erosive disease and lack of diagnostic and prognostic value. [ABSTRACT FROM AUTHOR]

Objective: The focus of this study was to assess changes in the cumulative incidence of extra‐articular manifestations of rheumatoid arthritis (ExRAs) and associated mortality risk. Methods: This study evaluated trends in occurrence of ExRAs using a population‐based inception cohort that included all adult patients with incident rheumatoid arthritis (RA) from 1985 through 2014 meeting the 1987 American College of Rheumatology criteria. Patients were divided into two cohorts based on the incidence date of RA, 1985 to 1999 and 2000 to 2014. The occurrence of ExRAs was determined by manual chart review, and the 10‐year cumulative incidence was estimated for each ExRA in both cohorts. Cox proportional hazard models were used to determine associations between specific demographic and RA disease characteristics and ExRAs and between ExRAs and mortality. Results: There were 907 patients included, 296 in the 1985 to 1999 cohort and 611 in the 2000 to 2014 cohort. The 10‐year cumulative incidence of any ExRA decreased significantly between the earlier and later cohorts (45.1% vs 31.6%, P < 0.001). This was largely driven by significant declines in subcutaneous rheumatoid nodules (30.9% vs 15.8%, P < 0.001) and nonsevere ExRAs (41.4% vs 28.8%, P = 0.001). Identified risk factors for the development of any ExRAs include rheumatoid factor positivity (hazard ratio [HR] 2.02, 95% confidence interval [CI] 1.43–2.86) and current smoking (HR 1.61, 95% CI 1.10–2.34). Mortality was increased in patients with either nonsevere (HR 1.83, 95% CI 1.18–2.85) or severe ExRAs (HR 3.05, 95% CI 1.44–6.49). Conclusions: The incidence of ExRAs has decreased over time. Mortality remains increased in patients with ExRAs. [ABSTRACT FROM AUTHOR]

Problem: Studies on subsequent pregnancy loss prediction models specific for recurrent pregnancy loss (RPL) patients are very limited. This study aims to develop a risk predictive model based on the immunological parameters for the subsequent pregnancy loss risk in northwest Chinese RPL patients. Method of study: Totally of 357 RPL patients recruited from Lanzhou University Second Hospital were included in this retrospective study. Univariate analysis was performed on RPL patients with outcomes of live birth or pregnancy loss. Subsequently, the least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to select variables among baseline and clinical characteristics and to develop a pregnancy loss risk prediction model with all 357 RPL patients. The area under the curve (AUC), calibration curve and decision curve analyses were used to evaluate the performance of the prediction model; moreover, 10‐fold cross‐validation was used for internal validation. Results: Ten factors of maternal age, age of menarche, previous pregnancy loss, IL‐10, complement 4, IgA, antiprothrombin antibody IgG/IgM, rheumatoid factor IgA, and lupus anticoagulant (LA) 1/LA2 ratio were finally selected as variables for the prediction model of pregnancy loss risk. The AUC value and Hosmer–Lemeshow test p‐value of the model were.707 and.599, respectively, indicating a satisfactory discrimination and calibration performance. Moreover, the clinical decision curve suggested this prediction model have a good positive net benefit. Conclusions: This is the first prediction model for the risk of subsequent pregnancy loss in northwest Chinese women with RPL, providing a user‐friendly tool to clinicians for the early prediction and timely management of RPL patients. [ABSTRACT FROM AUTHOR]

Objective: Rheumatoid factor (RF) and anti‐cyclic citrullinated peptide antibody (anti‐CCP) are commonly used for diagnosis of rheumatoid arthritis (RA), although other rheumatic diseases with arthritis can test positive. This study aimed to determine the cutoff values for RF and anti‐CCP with the best diagnostic performance in a sample of patients with RA, compared with other rheumatic diseases. Methods: This was a descriptive, prospective study. EUROINMMUN enzyme‐linked immunosorbent assays for RF isotypes immunoglobulin (Ig) A (IgA), IgG and IgM and third‐generation assay IgG for anti‐CCP were used in serum samples of patients with RA, other rheumatic diseases and healthy subjects. The cutoff with the best diagnostic performance was determined by the Youden Index and receiver operating characteristic analysis Results: Three hundred and thirty‐two serum samples were analysed. The cutoffs proposed in our population were for RF in RA patients versus other rheumatic diseases, and healthy subjects IgM 135 IU/mL, for each disease, compared with RA, were psoriatic arthritis (Psa) IgA 47.2 IU/mL, clinically suspicious arthralgia (CSA) IgA 39.5 IU/mL, primary Sjögren's syndrome (pSS) IgM 180.6 IU/mL, systemic lupus erythematosus (SLE) IgA 42.6 IU/mL, primary fibromyalgia (pFM) IgM 68.6 IU/mL, osteoarthritis (OA) IgM 48 IU/mL, gout IgM 117 IU/mL and healthy IgM 16.3 IU/mL. For anti‐CCP, in RA patients versus other rheumatic diseases, and healthy subjects 6.95 IU/mL, for each disease, compared with RA, were Psa 6.8 IU/mL, CSA 9.95 IU/mL, pSS 20.7 IU/mL, SLE 6 IU /mL, pFM 11.8 IU/mL, OA 11.9 IU/mL, gout 5 IU/mL and healthy 5 IU/mL. Conclusion: Irrespective of the manufacturer's suggested cutoff, the RA versus differential diagnosis cutoffs must be considered. [ABSTRACT FROM AUTHOR]

Introduction: Family physicians are often the first healthcare providers to encounter patients with rheumatoid arthritis (RA) in Nigeria, given the paucity of rheumatology services nationwide. This study aimed to assess and address the knowledge gap regarding RA among family physicians in Nigeria. Methods: A cross‐sectional survey involving 609 family physicians from all six geopolitical zones of Nigeria was conducted in October 2022. Pre‐intervention questionnaires were administered to assess the participants' knowledge of RA. An investigator‐led PowerPoint presentation on RA was then delivered as an intervention, followed by the same participants completing post‐intervention questionnaires to evaluate knowledge improvement. Data were analyzed using the Statistical Package for Social Science, version 25. Results: The mean age of participants was 42 ± 15 years, predominantly male (63.9%). The median pre‐intervention knowledge score was 3.2 (IQR: 2.0–4.5), with 77.0% scoring <5. After the intervention, the median score significantly improved to 7.1 (IQR: 4.3–8.6) (p =.001), with 62.6% scoring >7. Significant improvements were observed in several knowledge areas where gaps existed pre‐intervention, including the understanding that NSAIDs are not the mainstay of management (p <.001), the effectiveness of glucosamine and chondroitin sulfate (p <.001), confidence in diagnosing RA (p =.016), the recognition of joint deformities as a characteristic feature (p <.001), and the understanding that rheumatoid factor is not definitive for diagnosis (p <.001). Conclusion: This study highlights the importance of interventions in closing the knowledge gap about RA diagnosis and management. We recommend the implementation of a comprehensive approach to rheumatology education and services by policymakers. [ABSTRACT FROM AUTHOR]

Background: Rowell syndrome (RS) is an uncommon condition characterized by erythema multiforme (EM)‐like lesions and lupus erythematosus. It is more common in females, and EM may be the first manifestation of the disease with positive autoantibodies, such as antinuclear antibody (ANA), SSA, SSB and rheumatoid factor. The pathogenesis of RS is unknown and is likely caused by drug induction, ultraviolet exposure and infection. Method: We describe a case of RS from China which presented as characteristic targetoid‐like lesions and chilblain‐like erythema on hands and feet. This is a case of RS in a female patient from the inpatient department of dermatology. Results: A 41‐year‐old female with systemic lupus erythematosus exhibited chilblain‐like erythema and characteristic EM lesions on her extremities. She tested positive for serum ANA (1:320) and anti‐double‐stranded DNA, as well as other autoantibodies. Systemic glucocorticoids and hydroxychloroquine worked effectively for her. Conclusion: The present case met diagnostic criteria of RS. Notably, there was a co‑occurrence of facial butterfly erythema, chilblain‐like erythema and EM lesions distributed on the limbs in this case. [ABSTRACT FROM AUTHOR]

In rheumatoid arthritis (RA), only a subset of patients develop irreversible bone destruction. Our aim was to identify a microRNA (miR)‐based osteoclast‐related signature predictive of erosiveness in RA. Seventy‐six adults with erosive (E) or nonerosive (NE) seropositive RA and 43 sex‐ and age‐matched healthy controls were recruited. Twenty‐five miRs from peripheral blood mononuclear cell (PBMC)‐derived osteoclasts selected from RNA‐Seq (discovery cohort) were assessed by qPCR (replication cohort), as were 33 target genes (direct targets or associated with regulated pathways). The top five miRs found differentially expressed in RA osteoclasts were either decreased (hsa‐miR‐34a‐3p, 365b‐3p, 374a‐3p, and 511‐3p [E versus NE]) or increased (hsa‐miR‐193b‐3p [E versus controls]). In vitro, inhibition of miR‐34a‐3p had an impact on osteoclast bone resorption. An integrative network analysis of miRs and their targets highlighted correlations between mRNA and miR expression, both negative (CD38, CD80, SIRT1) and positive (MITF), and differential gene expression between NE versus E (GXYLT1, MITF) or versus controls (CD38, KLF4). Machine‐learning models were used to evaluate the value of miRs and target genes, in combination with clinical data, to predict erosion. One model, including a set of miRs (predominantly 365b‐3p) combined with rheumatoid factor titer, provided 70% accuracy (area under the curve [AUC] 0.66). Adding genes directly targeted or belonging to related pathways improved the predictive power of the model for the erosive phenotype (78% accuracy, AUC 0.85). This proof‐of‐concept study indicates that identification of RA subjects at risk of erosions may be improved by studying miR expression in PBMC‐derived osteoclasts, suggesting novel approaches toward personalized treatment. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Aim: Certolizumab pegol (CZP), an Fc‐free, PEGylated tumor necrosis factor inhibitor (TNFi), has shown rapid and sustained reduction in signs and symptoms of rheumatoid arthritis (RA). Elevated rheumatoid factor (RF) level has been associated with RA disease progression and poorer TNFi response. We assessed the efficacy of CZP in patients with early and established RA across baseline RF levels. Methods: This post‐hoc analysis included data from 6 trials: C‐OPERA (NCT01451203), pooled RAPID trials (RAPID‐1 [NCT00152386], RAPID‐2 [NCT00160602], J‐RAPID [NCT00791999], RAPID‐C [NCT02151851]), and EXXELERATE (NCT01500278). Patients who received CZP or placebo/comparator with methotrexate (MTX) were categorized by baseline RF quartiles. Efficacy was assessed with Disease Activity Score‐28 erythrocyte sedimentation rate (DAS28‐ESR). Results: Overall, 316, 1537, and 908 patients were included in C‐OPERA, pooled RAPID trials, and EXXELERATE, respectively. Patient demographics and baseline disease characteristics were similar between treatment groups and across RF quartiles. DAS28‐ESR low disease activity (LDA) and remission (REM) rates were numerically higher in the CZP + MTX group than PBO + MTX group at weeks 12 and 24, across RF quartiles. LDA and REM rates in the CZP + MTX groups were comparable across RF quartiles at weeks 12 and 24. Mean DAS28‐ESR decreased from week 0 to week 24 in the CZP + MTX groups, across RF quartiles. Conclusion: CZP showed steady efficacy across baseline RF quartiles in patients with early and established RA, over 24 weeks. CZP treatment may be considered in patients with RA irrespective of baseline RF levels and time from diagnosis. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a severe inflammatory auto‐immune disorder affecting millions of people across the globe. The current therapeutic options are not adequate to address the complications of RA. Therefore, the present study was conducted to elucidate the protective effect of lariciresinol, a lignan, against Complete Freund's adjuvant (CFA)‐induced arthritis in rats. The results of the study showed that lariciresinol improves paw swelling and arthritic scores in rats as compared to CFA rats. Lariciresinol also showed a significant reduction in rheumatoid factor, C‐reactive protein, tumor necrosis factor‐α, interleukin (IL)‐17, and tissue inhibitor of metalloproteinases‐3 level with a simultaneous increase in IL‐4 level. The burden of oxidative stress was also reduced in CFA rats, as shown by reduced MDA levels and increased SOD and GPx after the administration of lariciresinol. In a Western blot analysis, lariciresinol showed a significant reduction of transforming growth factor‐β and nuclear factor‐κB (NF‐κB) protein levels in CFA rats. To understand the binding characteristic of lariciresinol with NF‐κB, molecular docking analysis was conducted, which showed Larciresinol interacted with the active site of NF‐κB. Our study demonstrated the significant protective effect of lariciresinol against RA via multi‐target action. [ABSTRACT FROM AUTHOR]

Aim: Many markers are used for clinical diagnosis in rheumatic diseases; rheumatoid factor (RF) is the most frequently used marker. However, RF is not specific to rheumatoid arthritis (RA). RF positivity is widely observed in patients with advanced age, infectious, autoimmune, and lymphoproliferative diseases. In this context, the objective of this study is to investigate the demographic characteristics, frequency of antinuclear antibody (ANA) and anti‐cyclic citrullinated peptide (anti‐CCP) positivity, hemogram parameters and distribution of the diagnoses in RF‐positive patients followed at the rheumatology clinic. Methods: The population of this retrospective study consisted of patients above 18 years of age who were referred to have RF positivity by nephelometric method at Kahramanmaraş Necip Fazıl City Hospital Rheumatology Clinic between January 2020 and June 2022. Results: The mean age of the 230 patients with a positive RF test result, 155 (76%) male and 55 (24%) female, was 52.7 ± 15.5 years. There were 81 (35.2%), 54 (23.5%), 73 (31.7%) and 22 (9.6%) patients with RF levels between 20 and 50 IU/mL, 50 and 100 IU/mL, 100 and 500 IU/mL, and above 500 IU/mL, respectively. There was no significant difference detected between the groups that were created based on the RF titers regarding demographic characteristics (P > 0.05). The rate of being diagnosed with any rheumatic disease was significantly lower in the group with RF levels between 20 and 50 IU/mL compared to other groups (P = 0.001). The distribution of rheumatic and non‐rheumatic disease diagnoses according to RF levels did not reveal any significant difference between the groups (P = 0.369 and P = 0.147, respectively). RA was the most common (62.2%) rheumatic disease diagnosis among the patients included in the study. The leukocyte count was significantly higher in the group with RF levels above 500 IU/mL compared to the group with RF levels between 20 and 50 IU/mL (P = 0.024). There was no significant difference between the groups in other laboratory results, that is, hemogram, sedimentation, C‐reactive protein, platelet, and lymphocyte/monocyte ratio (P > 0.05). Conclusion: The study findings indicate that RF positivity can be seen in the context of different rheumatological diseases; hence RF levels alone may not predict rheumatological disease. There was also no significant relationship between RF levels and ANA and anti‐CCP positivity. The most common diagnosis in patients presenting with elevated RF levels was RA. Nevertheless, it should be noted that RF can be found asymptomatically in the general population. [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]

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]

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: 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]

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]

Rheumatoid arthritis (RA) affects approximately 1.5% of the population worldwide and 0.5–3.3% of the Mexican population. The presence of rheumatoid factor (RF), anti‐citrullinated protein antibodies (ACPA) and anti‐carbamylated protein (anti‐CarP) antibodies has been described in populations at risk of RA development, such as first‐degree relatives (FDR). Anti‐CarP antibodies are present in RA patients (44%), FDR of RA patients (18%) and healthy controls (4.7%). Anti‐CarP antibodies have not been described in FDR of the Mexican population. The objective of this study was to determine the prevalence of Rheumatoid Factors (RF) isotypes, ACPA and anti‐CarP antibodies isotypes in FDR of RA patients. An observational, cross‐sectional study, in an FDR of RA cohort, was performed. We measured IgA, IgG and IgM isotypes of RF, ACPA and anti‐CarP antibodies. A total of 144 FDRs from 99 RA patients were enrolled. The prevalence of anti‐CarP antibodies was 2.8% for IgA, 4.2% for IgG, whereas IgM was not detected. The serologic association was for RF/ACPA 4.48%, RF/anti‐CarP 2.7%, FR 64.5%, ACPA 1.3%, ACPA/anti‐CarP 0.69%, anti‐CarP 3.4%, and no RF/ACPA/anti‐CarP was observed. We found a low prevalence of anti‐CarP antibodies in our cohort of FDR of RA patients, but the prevalence of ACPA and RF were higher than other cohorts previously reported. [ABSTRACT FROM AUTHOR]

Background: This study analyzed the association between autoantibody types and salivary gland hypofunction in patients with primary Sjögren's syndrome (pSS). Methods: A retrospective analysis was performed on patients who visited the Department of Orofacial Pain and Oral Medicine at Yonsei University Dental Hospital from January 1, 2010 to May 31, 2021, and who were diagnosed with pSS. Out of 191 patients who fulfilled the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria, 50 were positive for both anti‐Ro/SSA and anti‐La/SSB, whereas 97 had anti‐Ro/SSA but not anti‐La/SSB antibodies. Forty‐four patients for whom neither anti‐Ro/SSA nor anti‐La/SSB antibodies were found were diagnosed with Sjögren's syndrome by minor salivary gland biopsy. Results: The anti‐Ro/SSA antibody‐positive group showed higher rheumatoid factor (RF) levels than the anti‐Ro/SSA antibody‐negative group. The anti‐La/SSB antibody‐positive group showed lower unstimulated whole saliva (UWS), stimulated whole saliva (SWS), higher erythrocyte sedimentation rate and RF level than the anti‐La/SSB antibody‐negative group. In addition, the group with both anti‐Ro/SSA and anti‐La/SSB antibodies showed lower UWS than the group with only anti‐Ro/SSA antibodies. However, there were no significant differences in UWS or SWS after taking pilocarpine, and C‐reactive protein. Conclusions: UWS and SWS were lower when a patient was positive for anti‐La/SSB, showing that anti‐La/SSB is more likely to be involved in salivary gland hypofunction than anti‐Ro/SSA in patients with pSS. Therefore, performing laboratory tests, including anti‐La/SSB, helps predict the prognosis of salivary gland function in patients with suspected pSS. [ABSTRACT FROM AUTHOR]

POST-TRANSLATIONALLY MODIFIED NEOANTIGEN-BASED DISEASE ACTIVITY ASSESSMENT Neoantigen-specific self-reactive T cell assessment The production and activation of self-reactive T cells is an important part in antigen-specific autoimmune damage. The PTM neoantigen-based autoimmune diseases diagnostic strategy mainly contains two parts: neoantigen-based disease risk assessment and disease activity assessment (Figure 1). Keywords: metabolite; neoantigen; post-translational modification; self-reactive T cell EN metabolite neoantigen post-translational modification self-reactive T cell 1 3 3 08/30/23 20230801 NES 230801 GENERATION OF POST-TRANSLATIONALLY MODIFIED NEOANTIGEN IN AUTOIMMUNE DISEASES Autoimmune diseases can be caused by emerging neoantigens that break immune tolerance in humans. [Extracted from the article]

Dermatomyositis (DM) is a poorly prognostic autoimmune disease the pathogenesis of which is multifactorial and not clearly defined. DM may be influenced by genes, environment, and immunity. The typical manifestations of DM are Gottron rash, heliotrope rash, rash on the shoulders and buttocks, erythema around fingernails, excessive keratosis of the epidermis, mechanic's hands, and interstitial lung disease (ILD), among others. Anti‐melanoma differentiation‐associated 5 gene (MDA5) antibody has been strongly associated with DM. Furthermore, anti‐SSA/Ro52 antibody has been reportedly associated with DM. A 49‐year‐old woman presented with cough, expectoration, and dyspnea. Relevant examinations revealed elevated levels of muscle enzyme, double‐positive anti‐MDA5 and anti‐SSA/Ro52 antibodies, positive rheumatoid factor, and a high titer of anti‐citrullinated protein antibody. DM overlapping rheumatoid arthritis with ILD was confirmed. We suggest the use of glucocorticoids combined with immunosuppressant therapy, supplemented with gastric and liver protection, and recommend the use of intravenous immunoglobulins and rituximab. [ABSTRACT FROM AUTHOR]

Background and objective: Rheumatoid arthritis (RA) is a frequent cause of interstitial lung disease (ILD); however, the impact of rheumatoid factor and anti‐citrullinated peptide antibody seropositivity in ILD without connective tissue disease (CTD) is unclear. We examined the association of seropositivity with ILD progression, mortality and response to immunosuppression in non‐CTD ILD. Methods: A total of 1570 non‐CTD patients (with idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, interstitial pneumonia with autoimmune features or unclassifiable ILD) and 181 RA‐ILD patients were included from a prospective registry. Longitudinal forced vital capacity (FVC), transplant‐free survival and incidence of progressive fibrosing‐ILD (PF‐ILD) were compared between seronegative non‐CTD ILD (reference group), seropositive non‐CTD ILD and RA‐ILD using linear mixed‐effect and Cox proportional hazards models adjusted for age, sex, smoking pack‐years and baseline FVC. Interaction between seropositivity and immunosuppression on FVC decline was assessed in patients with ≥6 months of follow‐up before and after the treatment. Results: Two hundred and seventeen (13.8%) patients with seropositive non‐CTD ILD had similar rates of FVC decline and transplant‐free survival compared to seronegative non‐CTD ILD, but more frequently met the criteria for PF‐ILD (hazard ratio [HR] = 1.35, p = 0.004). RA‐ILD had slower FVC decline (p = 0.03), less PF‐ILD (HR = 0.75, p = 0.03) and lower likelihood of lung transplant or death (HR = 0.66, p = 0.01) compared to seronegative non‐CTD ILD. No interaction was found between seropositivity and treatment on FVC decline in non‐CTD ILD. Conclusion: Seropositivity in non‐CTD ILD was not associated with improved outcomes or treatment response, highlighting the importance of other disease features in determining prognosis and predicting response to immunosuppression. We show that rheumatoid factor and anti‐citrullinated peptide antibody are not associated with outcomes or response to immunosuppression in patients with interstitial lung diseases not due to connective tissue disease, indicating the need for future studies to test the prognostic impact of other clinical and radiological features that may predict response to therapy. See relatedEditorial [ABSTRACT FROM AUTHOR]

Background: Lameness is one of the major causes of reduced physical performance and early retirement in working horses. TamaFlex™ (NXT15906F6) is a standardized synergistic anti‐inflammatory botanical formulation containing Tamarindus indica seed extract and Curcuma longa rhizome extract at a 2:1 ratio. Methods: We conducted a 12‐week single‐center, randomized, blinded, placebo‐controlled trial demonstrating the efficacy of NXT15906F6 in horses with lameness grade 2–4 on the American Association of Equine Practitioners (AAEP) scale. Twenty‐two lame horses were supplemented with NXT15906F6 (2.5 gram/day) or placebo over a period of 84 days. Improvement in lameness over placebo was the primary endpoint, and changes in the levels of rheumatoid factor (RF), anti‐nuclear antibody (ANA), and anti‐cyclic citrullinated peptide (ACC‐peptide) in serum, and pro‐inflammatory cytokines including interleukin (IL‐1β and IL‐6), tumor necrosis factor‐α (TNF‐α) and prostaglandin‐E2 (PGE2) in serum and synovial fluid were the secondary endpoints. Results: NXT15906F6 exhibited significant relief from lameness in a time‐dependent manner. NXT15906F6 also reduced levels of ANA, PGE2, IL‐1β, TNF‐α and IL‐6. Moreover, NXT15906F6 supplementation is safe and tolerable in alleviating joint pain in lame horses, and protects the joints from further degradation by reducing pro‐inflammatory mediators. Conclusion: NXT15906F6 significantly reduces the lameness during walking and trotting, leading to an improvement in their joint flexibility, health, and working performances. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate a composite rheumatoid arthritis (RA) disease activity index using optical spectral transmission (OST) scores obtained with the HandScan, replacing tender and swollen joint counts. Methods: RA patients from a single center routinely undergoing HandScan measurements with at least 1 concurrent OST score and Disease Activity Score in 28 joints (DAS28) were included. Data were extracted from medical records. Linear regression analyses with the DAS28 as the outcome were performed to create a disease activity index (DAS‐OST). OST score, erythrocyte sedimentation rate (ESR), and patient global assessment (PtGA) visual analog scale (VAS), sex, age, disease duration, and rheumatoid factor status were evaluated as independent variables. Final models were derived based on the statistical significance of coefficients and model fit. Of the data, two‐thirds were used for development and one‐third for validation; external validation was performed in a cohort from another center. Agreement between DAS‐OST and DAS28 was assessed using the Bland‐Altman plot method and intraclass correlation coefficient (ICC). Diagnostic value of the DAS‐OST was determined for established definitions of remission, low disease activity (LDA), and high disease activity (HDA). Results: Data of 3,358 observations from 1,505 unique RA patients were extracted. DAS‐OST was defined as: –0.44 + OST × 0.03 + male × –0.11 + LN(ESR) × 0.77 + PtGA VAS × 0.03. The ICCs between DAS‐OST and DAS28 were 0.88 (95% confidence interval [95% CI] 0.87–0.90) and 0.82 (95% CI 0.75–0.86) and measurement errors were 0.58 and 0.87 in internal and external validation, respectively. Sensitivity for remission, LDA, and HDA was 79%, 91%, and 43%, respectively, and specificity was 92%, 80%, and 96% in external validation. Conclusion: Using the HandScan, RA disease activity can be accurately estimated if combined with ESR, PtGA VAS, and sex into a disease activity index (DAS‐OST). [ABSTRACT FROM AUTHOR]

Objective: To assess anti‐Ro52 and anti‐Ro60 serologic profiles as markers of clinically relevant phenotypic subsets of patients with Sjögren's syndrome (SS). Methods: From a cohort of 839 consecutive patients with suspected or established SS seen in our multidisciplinary SS center, we compared the association of key phenotypic features in 390 patients who fulfilled SS classification criteria and in the parent cohort, stratifed by the presence of both anti‐Ro60 and anti‐Ro52, anti‐Ro60 alone, and anti‐Ro52 alone. Results: The SS cohort included 227 patients (58%) with both anti‐Ro60 and anti‐Ro52, 65 (17%) with anti‐Ro60 alone, 58 (15%) with anti‐Ro52 alone, and 40 (10%) with neither antibody. Those with both anti‐Ro60 and anti‐Ro52 had a significantly increased prevalence of abnormal ocular surface staining, focal lymphocytic sialadenitis with focus score ≥1, antinuclear antibody ≥1:320, anti‐SSB/La, rheumatoid factor, and IgG ≥15.6 gm/liter (P < 0.0016 for all). The groups with isolated anti‐Ro52 and anti‐Ro60 were equivalent to each other in their phenotypic associations, except for rheumatoid factor, which was higher in the anti‐Ro52 alone group. The associations of these Ro antibody serologic profiles were similar in the parent cohort, except for additional associations with salivary gland enlargement and parotid gland ultrasound score. Conclusion: SS patients with both anti‐Ro60 and anti‐Ro52 antibodies are distinguished by a higher prevalence of markers of B‐cell hyperactivity and glandular inflammation. Antibody reactivity to both Ro60 and Ro52 may thus serve as an important inclusion criterion for SS patients in clinical trials where the therapeutic agent targets pathways mediating these pathogenic abnormalities. [ABSTRACT FROM AUTHOR]

The microbiome and faecal metabolome beta-diversity also showed differences between responders and non-responders (Figure 3D-F), likely reflecting the baseline differences in diet and gut microbiome. (A-C) Comparison of average Shannon diversity of the microbiome (A), faecal metabolome (B) or plasma metabolome (C) across three timepoints; paired samples Wilcoxon tests were performed to compare means of the Shannon diversity between the different timepoints. Changes in diet might modify the faecal microbiome and metabolomic profile, affecting pain in rheumatoid arthritis (RA). [Extracted from the article]

To explore the therapeutic value of lupeol on collagen‐induced arthritis (CIA) in rats, a rheumatoid arthritis model. Lupeol is well known pentacyclic triterpene found in various plant sources, which possess anti‐inflammatory and antioxidant actions. The current study was assessed the anti‐arthritic potential of lupeol and its molecular mechanisms as compared with indomethacin (Indo) in collagen‐induced arthritis CIA rats. The rats were randomly alienated into five groups: Control, CIA alone, CIA + lupeol (10 mg/kg bw), CIA + Indomethacin (3 mg/kg bw), and lupeol (10 mg/kg bw) alone. The paw volume, biochemical, hematological parameters, inflammatory enzymes, and cytokines were measured. As well protein expression of apoptotic proteins, and histopathological of ankle joint were examined. Inflammatory markers, cytokines, histological changes, paw volume, and inflammation were intensely reduced and enhanced apoptosis by lupeol. Alterations in hematological parameters, rheumatoid factor, C‐reactive protein, and ceruloplasmin in arthritis were reverted by lupeol. Protein expressions of Bcl‐2, and P13K/Akt signaling were declined, whereas the Bax, caspssae‐3, and caspase‐9 were elevated. These results highlighted that lupeol suppresses P13K/Akt signaling and has a promising anti‐arthritic potential for collagen‐induced rheumatic arthritis treatment. Hence lupeol would be suggested as an alternative natural source with potent anti‐inflammatory and apoptotic actions for chronic inflammatory disorders. [ABSTRACT FROM AUTHOR]

Objective: To test the ability of machine learning (ML) approaches with clinical and genomic biomarkers to predict methotrexate treatment response in patients with early rheumatoid arthritis (RA). Methods: Demographic, clinical, and genomic data from 643 patients of European ancestry with early RA (mean age 54 years; 70% female) subdivided into a training (n = 336) and validation cohort (n = 307) were used. The genomic data comprised 160 single‐nucleotide polymorphisms (SNPs) previously associated with RA or methotrexate metabolism. Response to methotrexate monotherapy was defined as good or moderate by the European Alliance of Associations for Rheumatology (EULAR) response criteria at the 3‐month follow‐up. Supervised ML methods were trained with 5 repeats and 10‐fold cross‐validation using the training cohort. Prediction performance was validated in the independent validation cohort. Results: Supervised ML methods combining age, sex, smoking, rheumatoid factor, baseline Disease Activity Score in 28 joints (DAS28) scores and 160 SNPs predicted EULAR response at 3 months with the area under the receiver operating curve of 0.84 (P = 0.05) in the training cohort and achieved a prediction accuracy of 76% (P = 0.05) in the validation cohort (sensitivity 72%, specificity 77%). Intergenic SNPs rs12446816, rs13385025, rs113798271, and ATIC (rs2372536) had variable importance above 60.0 and along with baseline DAS28 scores were among the top predictors of methotrexate response. Conclusion: Pharmacogenomic biomarkers combined with baseline DAS28 scores can be useful in predicting response to methotrexate in patients with early RA. Applying ML to predict treatment response holds promise for guiding effective RA treatment choices, including timely escalation of RA therapies. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a complex disease with several risk factors. The effects of blood metabolites on RA remains elusive. We conducted a genetic correlation scan to explore the relevance of blood metabolism with RA. Method: The genome‐wide association study (GWAS) dataset of RA(2014) was obtained from a large scale meta‐analysis, including 29,880 RA cases and 73,758 controls. The GWAS datasets of 529 blood metabolites were derived from a recently published study. Linkage disequilibrium score regression (LDSC) analysis was performed to evaluate the genetic correlation between each of the blood metabolite and RA(2014). Then we used another GWAS data of RA(2021) and blood metabolites for LDSC analysis to verify whether the same blood metabolites were genetically correlated with RA. Mendelian randomization (MR) analysis was then applied to assess the causal relationship between the significant blood metabolites identified by LDSC and RA(2014). Result: Six suggestive blood metabolites were identified for RA(2014), including 10‐Undecenoate (correlation coefficient = −0.1686, p value = 0.0394), isovalerylcarnitine (correlation coefficient = 0.1660 p value = 0.0273), proline (correlation coefficient = 0.1647, p value = 0.0145), pantothenate (correlation coefficient = −0.3311, p value = 0.0078), tyrosine (correlation coefficient = 0.1735, p value = 0.0010), X‐14057 (correlation coefficient = 0.2695, p value = 0.0373). We identified four blood metabolites may have genetic correlations with RA(2021), including oleoylcarnitine (correlation coefficient = 0.1927, p value = 0.0432), levulinate (correlation coefficient = 0.1008, p value = 0.0413), pantothenate (correlation coefficient = −0.2311, p value = 0.0180), tyrosine (correlation coefficient = 0.1301, p value = 0.0078). There are two identical blood metabolites were found to be related with RA: pantothenate and tyrosine. It was found that there was a significant positive causal relationship between RA (exposure) and 10‐Undecenoate (outcome) (β = 0.0077, SE = 0.0033, p = 0.0192) by MR analysis. Conclusion: We investigated the genetic correlation and causal relationship between RA and blood metabolites by LDSC and MR analysis. These results may provide novel insights into the genetic mechanism of RA. [ABSTRACT FROM AUTHOR]

Objective: Palindromic rheumatism (PR) is characterized by self‐resolving and short duration attacks of arthritis/periarthritis. The present study was performed to report the results of PR treatment with methotrexate (MTX). Methods: We reviewed the charts of 152 patients with diagnosis of PR. Inclusion criteria were diagnosis of PR according to the criteria of Weismann, age ≥16, active disease and treatment with MTX for at least 6 months. Disease outcome was assessed by reaching remission and prevention of disease evolution to chronic arthritis. Remission was defined as stopping the attacks for 12 weeks and prednisolone dose ≤5 mg/d. MTX treatment failure was defined as failure to achieve remission, the need to add other disease‐modifying antirheumatic drugs and disease progression to chronic arthritis. Results: Fifty‐nine patients were included in the study. Median duration of follow‐up was 43 months. Attacks were controlled in 89.8% of patients. In 80% of the patients remission occurred during 12 months after starting treatment with MTX. Treatment failed in 20.3% of patients. Wrist joint involvement and positive rheumatoid factor (RF) were significantly more common in the MTX treatment‐failed group. In RF positive patients evolution to rheumatoid arthritis was more common than in RF negative patients. No significant differences were observed in remission rate and evolution to rheumatoid arthritis in anticitrullinated C peptide positive and negative patients. Conclusions: The present study, demonstrated the efficacy of MTX in controlling PR in seropositive and seronegative patients over a median of 43 months of treatment. [ABSTRACT FROM AUTHOR]

Objective: We quantified inflammatory burden in rheumatoid arthritis (RA) synovial tissue by using computer vision to automate the process of counting individual nuclei in hematoxylin and eosin images. Methods: We adapted and applied computer vision algorithms to quantify nuclei density (count of nuclei per unit area of tissue) on synovial tissue from arthroplasty samples. A pathologist validated algorithm results by labeling nuclei in synovial images that were mislabeled or missed by the algorithm. Nuclei density was compared with other measures of RA inflammation such as semiquantitative histology scores, gene‐expression data, and clinical measures of disease activity. Results: The algorithm detected a median of 112,657 (range 8,160‐821,717) nuclei per synovial sample. Based on pathologist‐validated results, the sensitivity and specificity of the algorithm was 97% and 100%, respectively. The mean nuclei density calculated by the algorithm was significantly higher (P < 0.05) in synovium with increased histology scores for lymphocytic inflammation, plasma cells, and lining hyperplasia. Analysis of RNA sequencing identified 915 significantly differentially expressed genes in correlation with nuclei density (false discovery rate is less than 0.05). Mean nuclei density was significantly higher (P < 0.05) in patients with elevated levels of C‐reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and cyclized citrullinated protein antibody. Conclusion: Nuclei density is a robust measurement of inflammatory burden in RA and correlates with multiple orthogonal measurements of inflammation. [ABSTRACT FROM AUTHOR]

Recently, an update on the analyses of the immunoglobulin heavy variable region chain (IGHV-IGHD-IGHJ) gene rearrangements of a comprehensive cohort, now containing 29 856 cases of chronic lymphocytic leukaemia (CLL), was reported by the European Research Initiative on CLL (ERIC) consortium.1 Within this collection, as many as 2195 stereotyped B-cell receptor (BCR) subsets have been defined ranging in size from 2 to 764 IGHV sequences. ht 1 Stereotyped rheumatoid factors (RFs) expressed by MALT lymphomas (MALT-L) have been described previously.8 The numbers of stereotyped RFs expressed by salivary gland MALT-L have been updated. Higher-order of chronic lymphocytic leukaemia (CLL) classification: shared antigenic specificities of stereotyped B-cell receptor subsets as defined by the European Research Initiative on CLL consortium Identification of a novel stereotypic IGHV4-59/IGHJ5-encoded B-cell receptor subset expressed by various B-cell lymphomas with high affinity rheumatoid factor activity. [Extracted from the article]

See related article [ABSTRACT FROM AUTHOR]

Introduction: Extra-articular involvement (EAI) in rheumatoid arthritis (RA) is rare, severe and usually presents after years of joint involvement. Onset of RA as lung involvement has been published. We describe a series of three patients with strongly positive anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF) positive in the absence of joint symptoms, but with significant EAI. Methods: This is a descriptive case series of three patients evaluated in an academic medical center rheumatology clinic. Results: A 50-year-old female presented with severe recurrent scleritis in the background of strongly positive ACPA, but no joint involvement. Her ocular disease responded well to rituximab. Four years later, she developed peripheral inflammatory arthritis consistent with RA. A 74-year-old male presented after developing recurrent steroid-dependent serositis (pleuro-pericarditis) and interstitial lung disease (ILD). Serology was notable for strongly positive ACPA, but no joint involvement. Serositis responded well to adalimumab. Two years after initial symptoms, he developed peripheral joint involvement after holding adalimumab. A 56-year-old female presented with an isolated, biopsyproven subcutaneous rheumatoid nodule. Subsequently, she developed pancytopenia and fatigue. She tested strongly positive for ACPA and RF. Bone marrow biopsy was negative for malignancy and she had no evidence of infection. She responded to steroids and hydroxychloroquine and had not developed joint involvement after 2 years of follow-up. Conclusion: EAI as an onset of RA is a complex and not easily recognized entity if typical joints involvement is not yet present. Early diagnosis may help guide specific therapy and prevent sequelae and co-morbidities. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis and periodontitis are chronic inflammatory diseases defined respectively by the destruction of the articular cartilage and tooth-supporting periodontal tissues. Although the epidemiologic evidence for an association between these two diseases is still scarce, there is emerging scientific information linking specific bacterial periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, in the citrullination process, leading to autoantibody formation and compromised immunotolerance of the susceptible patient to rheumatoid arthritis. In this review, we update the existing information on the evidence, not only regarding the epidemiologic association, but also the biologic mechanisms linking these two diseases. Finally, we review information emerging from intervention studies evaluating whether periodontal treatment could influence the initiation and progression of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prevalence of elevations of anti‐cyclic citrullinated peptide‐3 (anti‐CCP3) antibody, rheumatoid factor IgM (RF‐IgM) and serum calprotectin (sCP) in pre–rheumatoid arthritis (RA) as well as the diagnostic accuracies of these biomarkers for the timing of diagnosis of future RA. Methods: A total of 215 RA cases, each with approximately three pre‐RA diagnoses and one post–RA diagnosis serum sample, and controls were identified from the Department of Defense Serum Repository. All case samples and a single sample from each control subject were tested for anti‐CCP3 (IgG), RF‐IgM, and sCP. The diagnostic accuracies of biomarkers for future RA were evaluated. Results: Anti‐CCP3, RF‐IgM, and sCP were elevated in pre‐RA, with anti‐CCP3 and sCP significantly elevated compared with RF‐IgM at the earliest time points. Within the cases, the combination of anti‐CCP3 and RF‐IgM positivity had a positive predictive value (PPV) of 35.6% for a diagnosis of RA in 3 years or less, which is significantly higher than the PPV of 18.7% for anti‐CCP3 positivity alone (P < 0.001). A combination of anti‐CCP3, RF‐IgM, and sCP had the highest PPV (53.0%) for a diagnosis of RA in 3 years or less; however, this was not significantly higher than the PPV for anti‐CCP3 and RF‐IgM positivity (P = 0.248). Conclusion: Anti‐CCP3, RF‐IgM, and sCP are elevated in pre‐RA; furthermore, combinations of elevations of these biomarkers are more commonly seen in the period of less than or equal to 3 years to diagnosis. This may be considered in creating inclusion criteria in prevention trials in RA. In addition, the biologic relationships of these biomarkers in pre‐RA need exploration. [ABSTRACT FROM AUTHOR]

Aim: The increased level of interleukin‐6 (IL‐6) plays a significant role in the pathogenesis of rheumatoid arthritis (RA). Specific blockade of IL‐6 or its receptor has been used successfully in treating RA. MicroRNAs can regulate gene expression and act as regulators of target genes. Manipulation of specific microRNAs provides a novel therapeutic strategy for treating/preventing diseases. This study explored the role of miR‐98‐5p in the regulation of IL‐6 expression in rheumatoid fibroblast‐like synoviocytes (RA‐FLSs). Methods: Real‐time PCR was used to detect miR‐98‐5p expression in RA‐FLSs and normal human fibroblast‐like synovial cells (HFLSs). Site‐directed gene mutagenesis and reporter gene assay were performed to identify the interaction between miR‐98‐5p and IL‐6. Manipulation of miR‐98‐5p expression in RA‐FLS used transfection with miR‐98‐5p mimic or inhibitor. Stimulation of FLSs with IL‐1β induced IL‐6 production. Enzyme‐linked immunosorbent assay was used to detect the level of IL‐6 secreted into the RA‐FLS culture supernatant. Results: Compared with HFLSs, the expression of miR‐98‐5p in RA‐FLSs was significantly downregulated, and was negatively correlated with DAS28 scores and rheumatoid factor. In patients with anti‐keratin antibody‐positive RA, the expression level of miR‐98‐5p was lower. miR‐98‐5p negatively regulated the expression of IL‐6 in RA‐FLSs. After IL‐1β stimulation, the expression of miR‐98‐5p decreased and the level of IL‐6 protein was upregulated during IL‐6 secretion. Conclusion: These data suggest that manipulation of miR‐98‐5p, which negatively modulates IL‐6 expression, may be a potential clinical approach in RA. [ABSTRACT FROM AUTHOR]

Background/Objective: Psoriatic arthritis (PsA) is a chronic inflammatory illness. Approximately, 15% of psoriasis patients have undiagnosed PsA. In Mexico, we found no related studies. Our objective was to investigate the clinical–epidemiological characteristics of PsA in psoriasis patients in western Mexico. Methods: A cross‐sectional study including Mexican patients with clinical and histopathological diagnosis of psoriasis. Physical examination, rheumatoid factor analysis and radiographies of axial and peripheral skeleton were performed. The prevalence of PsA using the CASPAR criteria, age, sex; clinical variants of PsA, psoriasis type and the Psoriasis Area and Severity Index (PASI), were assessed. Descriptive and inferential statistics were used. Results: Of 90 patients with psoriasis, 48 met the criteria for PsA, with a prevalence of 53%, and average age of 50 ± 15 years. Predominating were, the female sex in 29 (60%), the axial variant of PsA in 24 (50%), and psoriasis plaques in 40 (83%). The average PASI was 12 ± 11. All cases were rheumatoid factor negative. These variables were not significantly different when comparing subjects with and without PsA, except for the female sex (60% vs. 7%; P < 0.001). Conclusions: Patients with psoriasis should intentionally be evaluated jointly Dermatologists and Rheumatologists searching joint involvement given the high prevalence of PsA previously undiagnosed. [ABSTRACT FROM AUTHOR]

Hyperviscosity syndrome (HVS) is a life‐threatening syndrome caused by high concentrations of large plasma proteins like IgM, rheumatoid factor, and other immune complexes, leading to increased blood viscosity and symptoms such as visual abnormalities, neurological impairment, bleeding diathesis, and thrombosis. While Waldenström's macroglobulinemia accounts for 80% to 90% of cases, HVS may develop in other clinical settings characterized by elevations in plasma proteins. Limited evidence currently exists describing the safety and efficacy of therapeutic plasma exchange (TPE) for the management of HVS secondary to non‐neoplastic conditions. We report a case of recurrent HVS associated with juvenile rheumatoid arthritis and Felty syndrome that demonstrated improvement in clinical symptoms following initiation of TPE. These findings suggest that TPE may be utilized as an adjunct treatment option in patients with HVS secondary to autoimmune disorders. [ABSTRACT FROM AUTHOR]