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Objective: To determine the correlation and clinical significance of musculoskeletal ultrasound semi-quantitative grading with bone salt metabolism, rheumatoid factor and erythrocyte sedimentation rate (ESR) in patients with rheumatoid arthritis. Methods: This is a clinical comparative study. A total of 240 patients with rheumatoid arthritis admitted to Baoding NO.1 Central Hospital were selected according to the DAS28 score of rheumatoid arthritis, and were divided into four groups, with 60 cases in each group from May 2020 to May 2022. The differences and correlation of musculoskeletal ultrasound semi-quantitative grading, bone metabolism indicators, erythrocyte sedimentation rate and rheumatoid factor among the four groups were statistically analyzed. Results: The scores of bone erosion, synovial hyperplasia, joint effusion and intrasynovial blood flow in Group-H were significantly higher than those in Group-R, L and M, with statistically significant differences(p=0.00). The procollagen Type-1 N-terminal propeptide(P1NP), bone-specific alkaline phosphatase(BALP) and osteoprotegerin(OPG) in Group-H were significantly lower than those in Group-R, L and M, with statistically significant differences(p=0.00); The tartrateresistant acid phosphatase(TRAC) in Group-H was significantly higher than that in Group-R, L and M, with a statistically significant difference(p=0.00). The levels of RF and ESR in Group-H were significantly higher than those in Group-R, L and M, with statistically significant differences(p=0.00). Conclusion: Musculoskeletal ultrasound semi-quantitative grading is correlated with the level of bone salt metabolism, rheumatoid factor and ESR in patients with rheumatoid arthritis. It can be combined with laboratory examination to objectively judge the severity of the course of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

The aim of this study is to characterise lupus-related arthritis and assess if the presence of ultrasound-detected erosions could be associated with belimumab in the treatment of systemic lupus erythematosus (SLE) articular manifestations. We performed a spontaneous, monocentric, retrospective, and observational study. We enrolled patients affected by SLE with articular involvement treated with belimumab. We excluded patients with positive rheumatoid factor (RF) or anti-citrullinated peptide antibody (ACPA), Jaccoud's arthropathy, and radiographic erosions. Patients were assessed at baseline, 3, and 6 months. We collected laboratory and clinical data from electronic records. Joint disease activity was assessed using disease activity score on 28 joints based on C-reactive protein (DAS28-CRP), swollen and tender joints count. All patients underwent an ultrasound examination of the wrist, metacarpophalangeal, proximal interphalangeal, and metatarsal-phalangeal joints before the initiation of treatment with belimumab. We performed Student's T-test and Mann–Whitney's U-test to assess the difference between means and Fisher's exact test to assess difference in proportions, and linear univariate regression to investigate predictors of disease activity. We enrolled 23 patients (female 82.6%, mean age of 50.65 ± 14.1 years). Seven patients (30.4%) presented bone erosions at baseline. Patients with bone erosions were generally older (61 ± 16.1 vs 46.13 ± 10.7 years, p = 0.016), more frequently male (42.8 vs 6.2%, p = 0.03), with higher baseline CRP levels (10.29 ± 11.6 vs 2.25 ± 3.1 mg/L, p = 0.015) and C4 levels (0.19 ± 0.17 vs 0.1 ± 0.04 g/L, p = 0.05). After 6 months of treatment with belimumab, patients without erosions improved their DAS28-CRP significantly (2.95 ± 0.89 vs 2.26 ± 0.48, p = 0.01), while patients with erosions did not (3.6 ± 0.79 vs 3.2 ± 0.95, p = 0.413). DAS28-CRP did not differ between the two groups at baseline, while it was significantly lower at the other two time points in patients without erosions. The majority of patients achieved remission at 6 months follow-up based on DAS28-CRP criteria (73.9%), with a significant difference between patients with and without erosions (42.8 vs 87.5%, p = 0.045). The presence of articular ultrasound-detected erosions could be predictive of a decreased efficacy of belimumab in the articular manifestations of SLE. A possible explanation is a rheumatoid-like articular phenotype, despite the lack of ACPA-positivity and radiologic erosions. However, due to the small sample population, larger cohorts are needed to assess the possible predictive role of this finding. Key Points • Ultrasound-detected, non-radiographic bone erosions are a common feature (around 30%) of patients with articular SLE. • Ultrasound-detected bone erosions at the beginning of the treatment were associated with a decreased efficacy of belimumab on the articular manifestations of SLE • Bone erosions could characterize a RA-like phenotype of articular involvement in SLE. [ABSTRACT FROM AUTHOR]

Objective：To evaluate the clinical diagnostic value of rheumatoid arthritis （RA） related autoantibodies based on magnetic particle chemiluminescence examination. Methods：RA related autoantibodies （anti-RA33, anti-CCP, RF, RF-IgM and RFIgG） detected in People's Hospital of Chongqing Banan District from September 2021 to March 2022 were analyzed retrospectively, including 105 patients with RA and 71 disease control groups. All autoantibodies were detected by acridine ester magnetic particle che⁃ miluminescence method. ROC curve was used to analyze diagnostic value of each test index for RA, and Spearman correlation analysis was used to analyze correlation between the test variables. Results：Serum levels of anti-CCP, RF, RF-IgG and RF-IgM in RA group were significantly higher than those in control group （P<0.05）, while there was no significant difference in anti-RA33 between two groups （P>0.05）； anti-CCP had the highest negative predictive value, positive predictive value and Youden index as diagnosis of RA, and anti-RA33 had the lowest sensitivity but the highest specificity as diagnosis of RA； RF-IgG has the highest sensitivity in diagnosis of RA. ROC curve analysis showed that AUC of anti-RA33, anti CCP, RF, RF-IgG and RF-IgM were 0.520，0.870，0.816，0.853 and 0.848, respectively. Spearman correlation analysis showed that there was a significant correlation among anti-CCP, RF, RF-IgG and RF-IgM （P<0.05）, while there was no significant correlation between anti-RA33 and these four indexes （P>0.05）. Conclusion：Sensi⁃ tivity of ani-RA33 is too low, hence it is easy to escape diagnosis or be misdiagnosed as preliminary screening test. RF, RF-IgG and RF-IgM had important diagnostic value for RA and can be used for the preliminary screening test of RA diseases. Anti-CCP is still the autoantibody with the highest diagnostic accuracy in the five autoantibodies, which can be used for the preliminary screening and confirmatory of RA. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate an individually tailored smoking-cessation intervention delivered in rheumatology care and compare the characteristics of patients who quit smoking with those who did not. This was an open single-group prospective intervention study over 24 months, with assessments at baseline and at 6, 12, 18, and 24 months. Current smokers with rheumatoid arthritis (RA) were invited to a smoking-cessation programme including behavioural change support, with or without pharmacotherapy. Data on disease activity, medical treatment, and patient-reported outcomes were retrieved from the Swedish Rheumatology Quality Register. The primary outcome was the proportion of patients at month 24 who reported having quit smoking with self-reported 7 day smoking abstinence. In total, 99 patients participated in the study. Median age was 58 years (interquartile range 50–64); 69% were female and 88% rheumatoid factor and/or anti-cyclic citrullinated peptide positive. At 24 months, 21% of the patients had quit smoking. At 6, 12, and 18 months, 12%, 12%, and 14% of patients, respectively, had quit smoking. For patients still smoking at 24 months, the median number of cigarettes per day was significantly reduced from 12 to 6 (p ≤ 0.001). Among patients who had quit smoking at 24 months, a smaller proportion reported anxiety at baseline compared to those still smoking (28% vs 58%, p = 0.02). A smoking-cessation intervention including behavioural change support with or without pharmacotherapy can be helpful for a substantial number of RA patients. Anxiety is associated with lower smoking-cessation success rates. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported the role of genes in different metabolic processes in the human body, and any variation in gene polymorphisms could lead to disturbances in these processes and different diseases. Objective: This study aimed to compare vitamin D receptor (VDR) FokI and TaqI genotypes in terms of parathyroid hormone (PTH) and some biomarkers of inflammation and susceptibility to rheumatoid arthritis (RA) disease. Methods: This study included 100 patients with rheumatoid arthritis (RA). Genotyping was performed by polymerase chain reaction (PCR) and examined by specific restriction enzymes using restriction fragment length polymorphism (RFLP). Serum intact PTH, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibodies (ACCPs) levels were measured. Results: An increased PTH level (> 65 pg/ml) was found in 8% of patients. No significant differences among FokI and TaqI vitamin D receptor genes polymorphism regarding positive and negative RF or ACCPs were found. A significant difference was found among FokI (p = 0.009) and none in TaqI genotypes regarding intact parathyroid hormone level categories. No significant correlation was found between the serum intact PTH level and ESR or CRP levels (P = 0.13 and 0.28, respectively). The parathyroid hormone level was not a good predictor for RF or ACCPs (P = 0.5 and 0.06, respectively). Conclusion: The FokI gene may play a role in controlling PTH levels in patients with RA. There was no significant correlation found between the serum intact PTH level and RA severity according to ESR and CRP inflammatory biomarkers. There are no differences between VDR genes FokI and TaqI polymorphism in terms of RA susceptibility (for RF and ACCPs). [ABSTRACT FROM AUTHOR]

Background: Rheumatoid Arthritis (RA) is a systemic and chronic autoimmune disease with inflammation at the synovial joints. The purposes of this study were to evaluate the correlation between serological variables and temporomandibular disorders (TMDs) in patients diagnosed with RA, evaluated through diagnostic criteria for temporomandibular disorders (DC/TMD), and to check the influence of comorbidities on the different TMD signs and symptoms, or any serological variables. Methods: This observational cohort research study included seventeen patients affected by RA. The comorbidities and some variables from the initial serological analyses were collected from the clinical rheumatological charts. Then, the presence of any of the following TMD signs/symptoms, temporal myalgia, temporomandibular joint arthralgia, click or crepitus, was evaluated through the symptom questionnaire of the DC/TMD during clinical evaluation following the DC/TMD examination form. Results: Rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA), and anti-nuclear antibody (ANA) positivity were present in 82.4%, 52.9%, and 41.2% of patients, respectively. Indicators of tissue inflammation were evaluated with median values of 21 mm/h for erythrocyte sedimentation rate (ESR) and 0.50 mg/dL for C-reactive protein (CRP). The RA patients presented comorbidities such as hypertension in 70.6% and diabetes in 23.5%. Negative ACPA had a significant association with myalgia (p = 0.03), and positive ANA was significantly associated with crepitus (p = 0.05). Conclusion: ANA and ACPA evaluation can be considered predictive serological tests associated with specific TMDs. Conversely, no influence of any comorbidities was found between different TMD signs and symptoms, or any serological variables. [ABSTRACT FROM AUTHOR]

Introduction: Our aim was to evaluate protein biomarker changes related to the administration of filgotinib, a Janus kinase (JAK) 1 preferential inhibitor, in patients with moderately to severely active rheumatoid arthritis (RA) with inadequate response to methotrexate. Methods: Plasma and serum samples were collected from patients enrolled in FINCH 1 (NCT02889796), a Phase 3 trial. Patients with stable backgrounds of methotrexate were randomly assigned once-daily oral filgotinib 200 or 100 mg, subcutaneous adalimumab 40 mg every 2 weeks (W), or placebo. Up to 35 biomarkers were analyzed at baseline, W4, and W12 with enzyme-linked immunosorbent assays and chemiluminescence and electrochemiluminescence assays. Results: At baseline, four distinct biomarker clusters were identified. The strongest intragroup correlations were in bone-cartilage resorption/inflammation and JAK/signal transducer and activator of transcription (STAT) signaling activity. At baseline, significant positive correlations were identified for cytokines with patient-reported pain and with patient measures of fatigue. Filgotinib reduced levels of cytokines associated with inflammation and cell migration as early as W4 and through W12. Compared to adalimumab, filgotinib induced significant reductions in bone-related turnover biomarkers, N-telopeptide of type 1 collagen and C-telopeptide 1, as well as biomarkers associated with baseline disease activity. No baseline predictors of therapeutic response to filgotinib were identified. Conclusions: Filgotinib reduced peripheral protein biomarkers associated with JAK/STAT signaling, inflammatory signaling, immune cell migration, and bone resorption as soon as W4 in FINCH 1. Effects were dose-dependent and consistent with the clinical efficacy of filgotinib observed in FINCH 1. The changes in peripheral biomarkers associated with filgotinib treatment in methotrexate-experienced patients are consistent with changes observed in both methotrexate-naïve and biologic disease-modifying antirheumatic drug-experienced RA populations. These data demonstrate dose-dependent effects of preferential JAK1 inhibition by filgotinib on peripheral blood protein biomarkers in methotrexate-experienced patients with RA. Trial Registration: ClinicalTrials.gov, NCT02889796. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheumatoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and ethnicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast–myofibroblast transition, epithelial–mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the histopathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies. [ABSTRACT FROM AUTHOR]

The programmed death-1 (PD-1) pathway has been shown to deliver an inhibitory signal, and aberrant expression of the PD-1 molecule and/or its ligand programmed death ligand 1 (PD-L1) has been demonstrated in human diseases, while its other ligand, programmed death ligand 2 (PD-L2), has rarely been studied. Here, we investigated the expression of PD-L2 in synovial tissue and blood from patients with rheumatoid arthritis (RA). Soluble PD-L2 and inflammatory cytokine levels in serum among healthy controls and patients with RA were compared via enzyme-linked immunosorbent assay (ELISA). Membrane PD-L2 on monocytes in blood was analyzed through flow cytometry (FCM). The different expression levels of PD-L2 between the RA and non-RA synovium were semi-quantified by immunohistochemical (IHC) staining. The soluble PD-L2 levels in serum from patients with RA were significantly lower than those in healthy subjects, correlating with active parameters (rheumatoid factor) and inflammatory cytokine secretion. The FCM results showed that patients with RA had significantly increased percentages of PD-L2-expressing CD14+ monocytes and correlated with inflammatory cytokines. PD-L2 expression on macrophages in the synovium from patients with RA was recorded by IHC staining with a higher score, and its correlation with pathological scores and clinical features was determined. Together, our results revealed aberrant expression of PD-L2 in RA, which may be a promising biomarker and therapeutic target associated with the pathogenesis of RA. [ABSTRACT FROM AUTHOR]

(1) Background: The aim of this study was to analyze labial minor salivary gland biopsy (MSGB) findings of a large sicca cohort and to examine their associations with Sjogren's syndrome (SS)-associated laboratory markers, phenotypic characteristics and systemic manifestations. Moreover, we sought to explore the ability of MSGB to identify SS patients among subjects with pre-diagnosed fibromyalgia (FM). (2) Methods: Included were all patients of three rheumatology departments having undergone a diagnostic MSGB within 9 years. Next to the examination of histological and immunohistochemical findings, we focused on activity and chronicity parameters of the underlying disease, autoantibodies, presence of systemic and hematologic involvement, as well as chronic pain and SS comorbidities. (3) Results: Among the 678 included patients, 306 (45.1%) had a positive focus score (FS). The remaining patients (n = 372) served as control subjects. There were significant correlations between FS and hypergammaglobulinemia (p < 0.001), ANA and rheumatoid factor positivity (both; p < 0.001), a weak significant correlation with erythrocyte sedimentation rate (rho = 0.235; p < 0.001) and a negative correlation with nicotine use (p = 0.002). Within the primary SS subgroup, FS was associated significantly with glandular enlargement (p = 0.007) and systemic hematologic manifestations (p = 0.002). Next to FS, CD20 cell staining showed an excellent diagnostic performance in the diagnosis of SS by an area under the curve of 0.822 (95%CI 0.780–0.864; p < 0.001). Interestingly, 42.1% of all patients with fibromyalgia (FM) having received an MSGB could be diagnosed with SS. (4) Conclusion: By examining one of the largest cohorts in the literature, we could show that MSGB histological and immunohistochemical findings not only play a key role in the classification and diagnosis of SS but could also provide important information regarding SS phenotype and systemic manifestations. Furthermore, MSGB may help differentiate patients with FM from patients with subclinical SS who suffer primarily from chronic pain. [ABSTRACT FROM AUTHOR]

The serological biomarker anti-citrullinated protein antibodies (ACPAs) may have several functions but is especially important for the diagnosis of rheumatoid arthritis (RA) along with clinical symptoms. This review provides an overview of ACPAs, which are useful in RA diagnostics and may improve our understanding of disease etiology. PubMed was searched with combinations of words related to antibodies recognizing epitopes containing the post-translationally modified amino acid citrulline in combination with rheumatoid arthritis; cyclic citrullinated peptide, CCP, anti-CCP, anti-citrullinated protein antibodies, ACPA, citrullination, peptide/protein arginine deiminase, PAD, filaggrin, vimentin, keratin, collagen, perinuclear factor, EBNA1, EBNA2, and others. From this search, we made a qualitative extract of publications relevant to the discovery, characterization, and clinical use of these antibodies in relation to RA. We highlight significant findings and identify areas for improvement. ACPAs have high diagnostic sensitivity and specificity for RA and recognize citrullinated epitopes from several proteins. The best-performing single epitope originates from Epstein–Barr Virus nuclear antigen 2 and contains a central Cit-Gly motif, which is recognized by ACPAS when located in a flexible peptide structure. In addition, ACPAs may also have prognostic value, especially in relation to early treatment, although ACPAs' main function is to aid in the diagnosis of RA. [ABSTRACT FROM AUTHOR]

Currently, multiple studies have indicated that CD8+ T lymphocytes play a role in causing damage to the exocrine glands through acinar injury in primary Sjögren's syndrome (pSS). The aim of this research was to assess the imbalance of circulating CD8+ T cell subsets. We analyzed blood samples from 34 pSS patients and 34 healthy individuals as controls. We used flow cytometry to enumerate CD8+ T cell maturation stages, using as markers CD62L, CD28, CD27, CD4, CD8, CD3, CD45RA and CD45. For immunophenotyping of 'polarized' CD8+ T cell subsets, we used the following monoclonal antibodies: CXCR5, CCR6, CXCR3 and CCR4. The findings revealed that both the relative and absolute numbers of 'naïve' CD8+ T cells were higher in pSS patients compared to the healthy volunteers. Conversely, the proportions of effector memory CD8+ T cells were notably lower. Furthermore, our data suggested that among patients with pSS, the levels of cytotoxic Tc1 CD8+ T cells were reduced, while the frequencies of regulatory cytokine-producing Tc2 and Tc17 CD8+ T cells were significantly elevated. Simultaneously, the Tc1 cell subsets displayed a negative correlation with immunoglobulin G, rheumatoid factor, the Schirmer test and unstimulated saliva flow. On the other hand, the Tc2 cell subsets exhibited a positive correlation with these parameters. In summary, our study indicated that immune dysfunction within CD8+ T cells, including alterations in Tc1 cells, plays a significant role in the development of pSS. [ABSTRACT FROM AUTHOR]

Background: Psoriatic arthritis is a chronic inflammatory illness. Nearly, 15% of psoriasis patients have undiagnosed psoriatic arthritis. Objective: The aim of this study was to investigate the prevalence of psoriatic arthritis and different clinical–epidemiological characteristics of the disease of patients. Materials and Methods: This cross-sectional study included psoriatic patients who attended Baghdad Teaching Hospital. Clinical examination, laboratory investigations including rheumatoid factor analysis and radiological examination of axial and peripheral skeleton were done. The prevalence of PsA, age, sex, clinical variants of PsA, and psoriasis type were assessed. Results: The prevalence of psoriatic arthritis was 0.02% during the period of study, mean age of participants was 44 ± 33. Obesity and overweight were reported by 34.75%, smoking by 24.58% with significant association with gender, also 28.81% with family history more in females. Regarding comorbidity, 33.9% of patients were suffering from metabolic syndrome, 23.72% with dyslipidemia, 22.88% with hypertension, and 17.8% with diabetes. Higher percentages (65.31%) of polyarthritis had family history followed by oligoarthritis (24.45%) and distal interphalangeal (10.20%). However, the association between types of arthritis was found to be statistically nonsignificant. Regarding the distribution of study sample according to the types of treatment, higher percentage of patients (72.88%) were on methotrexate (MTX) followed by NSAIDs (64.4%), while the lower percentage (4.7%) for Golimumab. Conclusions: A high percentage of comorbidities such as metabolic syndrome, diabetes mellitus, hypertension, dyslipidemia, and obesity were observed. Psoriasis vulgaris was the most common type of skin lesion associated with axial involvement. Family history was associated with oligoarthritis more than other types. The first choice of treatment was MTX. [ABSTRACT FROM AUTHOR]

Elderly-onset rheumatoid arthritis (EORA) is a distinct clinical entity defined as the onset of rheumatoid arthritis (RA) in individuals aged over 60 years. EORA presents unique clinical features, including a more equitable distribution of sexes, a potential predilection for male involvement, a higher incidence of acute onset characterized by constitutional symptoms, a propensity for systemic manifestations, elevated sedimentation rates at disease onset, a reduced occurrence of rheumatoid factor positivity, increased titers of anti-citrullinated protein antibodies, a preference for involvement of large joints, elevated disease activity, the presence of bone erosions, and heightened patient disability. RA is recognized to consist of three partially overlapping subsets. One subset mirrors the classical RA clinical presentation, while the remaining subsets exhibit either a polymyalgia rheumatica-like phenotype or present with remitting seronegative symmetrical synovitis accompanied by pitting edema syndrome. In the initial stages of EORA management, non-steroidal anti-inflammatory drugs (NSAIDs) are not typically the first-line treatment choice, because seniors are much more prone to develop side effects due to NSAIDs, and the use of NSAIDs is in reality contraindicated to the majority of seniors due to comorbidities. Disease-modifying antirheumatic drugs (DMARDs), frequently methotrexate, are introduced immediately after the diagnosis is made. In cases where elderly patients demonstrate resistance to conventional DMARD therapy, the introduction of biological or targeted synthetic DMARDs becomes a viable treatment option. EORA presents a unique clinical profile, necessitating tailored treatment strategies. Our study emphasizes the challenges of NSAID use in seniors, highlighting the imperative shift toward DMARDs such as methotrexate. Future research should explore personalized DMARD approaches based on disease activity, comorbidities, and safety considerations, aiming to optimize treatment outcomes and minimize glucocorticoid reliance, thereby enhancing the quality of care for EORA patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: About 40% of early undifferentiated arthritis (UA) progresses to rheumatoid (RA) or other chronic arthritis. Novel diagnostic tools predicting the risk for this progression are needed to identify the patients who would benefit from early aggressive treatment. Evidence on the role of single-nucleotide polymorphisms (SNPs) in the development of RA has emerged. The aim of our study was to investigate the association between rs2476601, rs833070, and rs6920220 SNPs and UA progression to RA. Materials and Methods: Ninety-two UA patients were observed for 12 months. At study entry, demographic and clinical characteristics were recorded, musculoskeletal ultrasonography was performed, and blood samples were drawn to investigate levels of inflammatory markers, rheumatoid factor (RF), anti-citrullinated protein antibodies (anti-CCP)detect SNPs. After 12 months, UA outcomes were assessed, and patients were divided into two (RA and non-RA) groups. The association between the risk of progression to chronic inflammatory arthritis and analyzed SNPs was measured by computing odds ratios (OR). Results: After a 12-month follow-up, 27 (29.3%) patients developed RA, and 65 (70.7%) patients were assigned to the non-RA group. The arthritis of 21 patients (22.8%) from the non-RA group resolved completely, while the other 44 (47.2%) patients were diagnosed with another rheumatic inflammatory disease. The patients who developed RA had a significantly greater number of tender and swollen joints (p = 0.010 and p = 0.021 respectively) and were more frequently RF or anti-CCP (p < 0.001), and both RF and anti-CCP positive (p < 0.001) at the baseline as compared with the patients in the non-RA group. No significant association between rs2476601 (OR = 0.99, p = 0.98), rs833070 (OR = 1.0, p = 0.97), and rs6920220 (OR = 0.48, p = 0.13) polymorphisms and the risk of developing RA were found. Conclusions: No association between analyzed SNPs and a greater risk to progress from UA to RA was confirmed, although patients with rs6920220 AA + AG genotypes had fewer tender joints at the disease onset. [ABSTRACT FROM AUTHOR]

BackgroundRheumatoid factors (RFs) are autoantibodies that target the Fc region of IgG, and are found in patients with rheumatic diseases as well as in the healthy population. Many studies suggest that an immune trigger may (transiently) elicit RF responses. However, discrepancies between different studies make it difficult to determine if and to which degree RF reactivity can be triggered by vaccination or infection.ObjectiveWe quantitatively explored longitudinal RF responses after SARS-CoV-2 vaccination and infection in a well-defined, large cohort using a dual ELISA method that differentiates between true RF reactivity and background IgM reactivity. In addition, we reviewed existing literature on RF responses after vaccination and infection.Methods151 healthy participants and 30 RA patients were included to measure IgM-RF reactivity before and after SARS-CoV-2 vaccinations by ELISA. Additionally, IgM-RF responses after a SARS-CoV-2 breakthrough infection were studied in 51 healthy participants.ResultsPublished prevalence studies in subjects after infection report up to 85% IgM-RF seropositivity. However, seroconversion studies (both infection and vaccination) report much lower incidences of 2-33%, with a trend of lower percentages observed in larger studies. In the current study, SARS-CoV-2 vaccination triggered low-level IgM-RF responses in 5.5% (8/151) of cases, of which 1.5% (2/151) with a level above 10 AU/mL. Breakthrough infection was accompanied by development of an IgM-RF response in 2% (1/51) of cases.ConclusionOur study indicates that de novo RF induction following vaccination or infection is an uncommon event, which does not lead to RF epitope spreading.

Background: To investigate the associations between extrahepatic manifestations, autoantibodies, and viremia in patients with hepatitis C virus (HCV) infection. Methods: This cross-sectional study recruited patients with HCV infection from the outpatient department of a tertiary medical center in Northern Taiwan between January 2017 and August 2019. Autoantibody profiles and the clinical parameters of HCV infection were evaluated using laboratory tests, and a questionnaire was used to record extrahepatic manifestations. HCV infection status, including inactive HCV infection, active hepatitis, and cirrhosis, was defined according to abdominal ultrasonography findings and alanine transaminase levels. Results: A total of 77 patients with HCV were recruited, with 19.5% and 16.9% of patients, respectively, presenting with arthritis and dry eyes. Autoantibody screening revealed rheumatoid factor (RF), antinuclear antibody (ANA), anti-Ro antibody, and anti-La antibody positivity in 20.8%, 23.4%, 13.0%, and 2.6% of the patients, respectively. The presence of RF was associated with arthritis, whereas the presence of ANA was associated with dry eyes but not dry mouth. Active hepatitis and HCV-related cirrhosis were associated with viremia, but not autoantibody profiles. Conclusion: In this single-center study, the prevalence of extrahepatic manifestations and autoantibodies did not differ in patients stratified by the HCV infection status. Rheumatic manifestations were associated with the presence of autoantibodies but not with viremia.

Abstract Introduction Our aim was to evaluate protein biomarker changes related to the administration of filgotinib, a Janus kinase (JAK) 1 preferential inhibitor, in patients with moderately to severely active rheumatoid arthritis (RA) with inadequate response to methotrexate. Methods Plasma and serum samples were collected from patients enrolled in FINCH 1 (NCT02889796), a Phase 3 trial. Patients with stable backgrounds of methotrexate were randomly assigned once-daily oral filgotinib 200 or 100 mg, subcutaneous adalimumab 40 mg every 2 weeks (W), or placebo. Up to 35 biomarkers were analyzed at baseline, W4, and W12 with enzyme-linked immunosorbent assays and chemiluminescence and electrochemiluminescence assays. Results At baseline, four distinct biomarker clusters were identified. The strongest intragroup correlations were in bone-cartilage resorption/inflammation and JAK/signal transducer and activator of transcription (STAT) signaling activity. At baseline, significant positive correlations were identified for cytokines with patient-reported pain and with patient measures of fatigue. Filgotinib reduced levels of cytokines associated with inflammation and cell migration as early as W4 and through W12. Compared to adalimumab, filgotinib induced significant reductions in bone-related turnover biomarkers, N-telopeptide of type 1 collagen and C-telopeptide 1, as well as biomarkers associated with baseline disease activity. No baseline predictors of therapeutic response to filgotinib were identified. Conclusions Filgotinib reduced peripheral protein biomarkers associated with JAK/STAT signaling, inflammatory signaling, immune cell migration, and bone resorption as soon as W4 in FINCH 1. Effects were dose-dependent and consistent with the clinical efficacy of filgotinib observed in FINCH 1. The changes in peripheral biomarkers associated with filgotinib treatment in methotrexate-experienced patients are consistent with changes observed in both methotrexate-naïve and biologic disease-modifying antirheumatic drug-experienced RA populations. These data demonstrate dose-dependent effects of preferential JAK1 inhibition by filgotinib on peripheral blood protein biomarkers in methotrexate-experienced patients with RA. Trial Registration ClinicalTrials.gov, NCT02889796.

Abstract Objective Rheumatoid factor (RF)-positive polyarthritis is the least common type of juvenile idiopathic arthritis (JIA). Functional disability in RF-positive polyarthritis patients is much more severe than in patients with other subtypes; but data on this subtype alone is limited. This study aimed to analyze clinical features, long-term follow-up, treatment response, and remission status in a large multicenter cohort of RF-positive polyarthritis patients. Methods This retrospective study included RF-positive polyarthritis patients that were followed up for ≥ 6 months between 2017 and 2022 by the Pediatric Rheumatology Academy (PeRA)-Research Group (RG). Data on patient demographics, clinical and laboratory characteristics were obtained from medical charts. JIA treatments and duration of treatment were also recorded. The patients were divided into 2 groups based on methotrexate (MTX) response, as follows: group 1: MTX responsive, group 2: MTX unresponsive. Clinical and laboratory findings were compared between the 2 groups. Results The study included 56 (45 female and 11 male) patients. The median age at onset of RF-positive polyarthritis was 13.2 years [(interquartile range) (IQR): 9.0–15.0 years] and the median duration of follow-up was 41.5 months (IQR: 19.5–75.7 months). Symmetrical arthritis affecting the metacarpophalangeal and proximal interphalangeal joints of the hands was commonly observed. Subcutaneous MTX was the preferred initial treatment; however, it was ineffective in 39 (69.6%) of the patients. Of 25 patients followed for 24 months, 56% still had active disease at 24 months. Conclusion During 2 years of treatment, 44% of RF-positive polyarthritis patients have inactive disease, and they should be considered as a distinct and important clinical entity requiring aggressive and early treatment.

Objectives—The aim of the present study was to characterize the clinical phenotype of patients with primary Sjögren’s syndrome (pSS) with non-identified antinuclear antibodies (ANA) in comparison with that of patients with pSS with negative ANA, positive typical ANA (anti-Ro/SSA and/or La/SSB) and positive atypical ANA. Methods—We conducted an observational, retrospective monocentric study at the Erasme University Hospital (Brussels, Belgium). Two hundred and thirty-three patients fulfilling the 2002 American–European Consensus Group criteria for pSS were included in this study. The patients were subdivided according to their ANA profile and demographics. The clinical and biological data of each subgroup were compared. Moreover, the relationships between these data and the ANA profiles were determined by multiple correspondence analysis. Results—In our cohort, 42 patients (18%) presented a non-identified ANA-positive profile. No statistically significant difference could be observed between non-identified ANA patients and ANA-negative patients in terms of age and/or ESSDAI score at diagnosis. There were significantly more frequent articular manifestations, positive rheumatoid factor (RF), and the use of corticosteroids in anti-Ro/SSA-positive patients compared to ANA-negative (p ≤ 0.0001) and non-identified ANA-positive patients (p ≤ 0.01). However, a significantly higher proportion of RF positivity and corticosteroid treatment was observed in non-identified ANA-positive patients compared to ANA-negative patients (p < 0.05). Conclusions—For the first time to our knowledge, our study has characterized the clinical phenotype of patients with pSS with non-identified ANA at diagnosis. The non-identified ANA-positive patients featured mostly a clinical phenotype similar to that of the ANA-negative patients. On the other hand, the non-identified ANA-positive patients were mainly distinguished from the ANA-negative patients by a greater proportion of RF positivity and the need for corticosteroid use due to articular involvement.

Abstract Introduction The efficacy of abatacept is enhanced in anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF)-positive versus -negative patients with rheumatoid arthritis (RA). Four early RA abatacept trials were analyzed to understand the differential impact of abatacept among patients with SeroPositive Early and Active RA (SPEAR) compared to non-SPEAR patients. Methods Pooled patient-level data from AGREE, AMPLE, AVERT, and AVERT-2 were analyzed. Patients were classified as SPEAR if they were ACPA +, RF +, disease duration

Background: To identify baseline predictors of persisting pain in children with Juvenile Idiopathic Arthritis (JIA), relative to patients with JIA who had similar baseline levels of pain but in whom the pain did not persist. Methods: We used data from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) inception cohort to compare cases of 'moderate persisting pain' with controls of 'moderate decreasing pain'. Moderate pain was defined as a Visual Analogue Scale (VAS) for pain measurement score of > 3.5 cm. Follow-up was minimum 3 years. Univariate and Multivariate logistic regression models ascertained baseline predictors of persisting pain. Results: A total of 31 cases and 118 controls were included. Mean pain scores at baseline were 6.4 (SD 1.6) for cases and 5.9 (1.5) for controls. A greater proportion of cases than controls were females (77.4% vs 65.0%) with rheumatoid factor positive polyarthritis (12.9% vs 4.2%) or undifferentiated JIA (22.6% vs 8.5%). Oligoarthritis was less frequent in cases than controls (9.7% vs 33%). At baseline, cases had more active joints (mean of 11.4 vs 7.7) and more sites of enthesitis (4.6 vs 0.7) than controls. In the final multivariate regression model, enthesitis count at baseline (OR 1.40, CI 95% 1.19–1.76), female sex (4.14, 1.33–16.83), and the overall Quality of My Life (QoML) baseline score (0.82, 0.69–0.98) predicted development of persisting pain. Conclusions: Among newly diagnosed children with JIA with moderate pain, female sex, lower overall quality of life, and higher enthesitis counts at baseline predicted development of persisting pain. If our findings are confirmed, patients with these characteristics may be candidates for interventions to prevent development of chronic pain. [ABSTRACT FROM AUTHOR]

Objective: There is an urgent need for novel biomarkers to improve the early diagnosis of rheumatoid arthritis (ERA). Current serum biomarkers used in the management of ERA, including rheumatoid factor and anti-cyclic citrullinated peptide (ACPA), show limited specificity and sensitivity. Here, we used metabolomics to uncover new serum biomarkers of ERA. Methods: We applied an untargeted metabolomics approach including gas chromatography time-of-flight mass spectrometry in serum samples from an ERA cohort (n=32) and healthy controls (n=19). Metabolite set enrichment analysis was performed to explore potentially important biological pathways. Partial least squares discriminant analysis and variable importance in projection analysis were performed to construct an ERA biomarker panel. Results: Significant differences in the content of 11/81 serum metabolites were identified in patients with ERA. Receiver operating characteristic (ROC) analysis showed that a panel of only three metabolites (glyceric acid, lactic acid, and 3-hydroxisovaleric acid) could correctly classify 96.7% of patients with ERA, with an area under the ROC curve of 0.963 and with 94.4% specificity and 93.5% sensitivity, outperforming ACPA-based diagnosis by 2.9% and, thus, improving the preclinical detection of ERA. Aminoacyl-tRNA biosynthesis and serine, glycine, and phenylalanine metabolism were the most significant dysregulated pathways in patients with ERA. Conclusion: A metabolomics serum-based biomarker panel composed of glyceric acid, lactic acid, and 3-hydroxisovaleric acid offers potential for the early clinical diagnosis of RA. [ABSTRACT FROM AUTHOR]

Background: Childhood-onset rheumatoid arthritis (CORA), known as rheumatoid factor (RF)-positive juvenile idiopathic arthritis is a type of juvenile idiopathic arthritis that shares the same genetic factors and clinical features as adult-onset rheumatoid arthritis. In Africa, CORA hasn't been the subject of a specific study. Objectives: The aim of this study is to describe the clinical features, disease activity, functional disability, and treatment of CORA at diagnosis in Senegal and compare the findings to other CORA populations. Methods: We conducted a mixed cohort study by reviewing the medical records of patients diagnosed with CORA with an age of symptom onset < 18 years according to the 2019 PRINTO provisional criteria for RF-positive JIA from January 2020 to December 2022 at rheumatology department of Aristide Le Dantec Hospital in Dakar, Senegal. We collected demographic, clinical, paraclinical and therapeutic data. Disease activity score was assessed by DAS28-ESR and DAS28-CRP. Functional disability was assessed using Health Assessment Questionnaire (HAQ) or Childhood HAQ. Results: A total of 21 patients were included. Eighteen (85.7%) were Females. The mean age at symptom onset was 13.0 ± 3.0 years, and at diagnosis was 16.4 ± 4.2 years. Morning stiffness, joint swelling, and joint deformities were found in 20, 18 and 13 patients respectively. Four patients had a family history of rheumatoid arthritis. Five patients had extra-articular involvement such as rheumatoid nodules. Two patients had interstitial lung disease. The biological inflammatory syndrome was found in 90% of cases. 16 of 21 (76.2%) patients had positive RF, and 18 of 20 (90%) patients had positive Anti-CCP. Seven of 12 (58.3%) patients had positive anti-nuclear antibodies. The mean DAS28-ESR was 5.7 ± 1.0. Fifteen (71.4%) patients had high disease activity (DAS28-ESR > 5.1). The mean DAS28-CRP was 5.4 ± 1.1. The median HAQ was 2.12 with a mean HAQ of 1.9. Nineteen (90.5%) patients were treated with methotrexate, while 17 (81%) had a combination of methotrexate and hydroxychloroquine. Oral prednisone was used in 17 (81%) cases. Non-steroidal anti-inflammatory drugs were used in 4 cases (19%). After 6 months of treatment, mean DAS28-CRP was 2.9. Conclusion: In our study, CORA mainly affects 13-year-old girls, characterised by high disease activity with joint deformity and significant functional impairment. Treatment is mainly based on methotrexate, prednisone and hydroxychloroquine. Further studies are needed to determine the exact clinical phenotype of this disease. [ABSTRACT FROM AUTHOR]

Introduction/objectives: The ASCORE study on treatment for rheumatoid arthritis (RA) showed better retention and clinical response rates for abatacept as first-line versus later-line therapy. This post hoc analysis of ASCORE assessed 2-year retention, efficacy, and safety of subcutaneous (SC) abatacept in Germany, Austria, and Switzerland. Methods: Adults with RA who initiated SC abatacept 125 mg once weekly were assessed. Primary endpoint was abatacept retention rate at 2 years. Secondary endpoints: proportions of patients with low disease activity (LDA)/remission per Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (≤ 3.2), Simplified Disease Activity Index (≤ 11), and Clinical Disease Activity Index (≤ 10). Outcomes were analyzed by treatment line and serostatus. Results: For the pooled cohort, the 2-year abatacept retention rate was 47.6%; retention was highest in biologic-naïve patients (50.5% [95% confidence interval 44.9, 55.9]). Patients seropositive for both anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF; + / +) at baseline had a higher 2-year abatacept retention rate than patients with single seropositivity for either APCA or RF or double-seronegativity (− / −), irrespective of treatment line. At 2 years, a higher proportion of patients who were biologic-naïve were in LDA/remission than patients with one or ≥ two prior biologics. Conclusion: A higher proportion of patients with + / + RA (compared with − / − RA) had abatacept retention after 2 years. Early identification of patients with seropositive RA may facilitate a precision-medicine approach to RA treatment, leading to a higher proportion of patients in LDA/remission. Trial registration number: NCT02090556; date registered: March 18, 2014 (retrospectively registered). Key Points • This post hoc analysis of a German-speaking subset of European patients with RA from the global ASCORE study (NCT02090556) showed that retention of SC abatacept within this subset was 47.6%, with good clinical outcomes after 2 years. • Patients with double-seropositive RA (ACPA and RF positive) had higher retention of abatacept than patients with double-seronegative RA (ACPA and RF negative). Retention and clinical responses were highest for patients who were biologic-naïve compared with patients who had one or ≥ two prior biologic treatments. • These real-world data may be useful for clinicians in informing individualized treatment pathways for patients with RA, and fostering superior disease control and clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Filgotinib (FIL) is a selective JAK1 inhibitor with an affinity 30-fold higher than JAK2, approved to treat moderate to severe active rheumatoid arthritis (RA), in adults with inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). Methods: We conducted a retrospective, multicentric study in order to evaluate efficacy and safety of FIL 200 mg daily therapy, after 3 and 6 months, in 120 patients affected by RA, managed in Tuscany and Umbria rheumatological centers. The following clinical records were analyzed: demographical data, smoking status, previous presence of comorbidities (Herpes zoster -HZ- infection, venous thromboembolism -VTE-, major adverse cardiovascular events -MACE-, cancer, diabetes, and hypertension), disease duration, presence of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), number of biological failures, and prior csDMARDs utilized. At baseline, and after 3 (T3) and 6 (T6) months of FIL therapy, we evaluated mean steroid dosage, csDMARDs intake, clinimetric indexes (DAS28, CDAI, HAQ, patient and doctor PGA, VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and body mass index (BMI). Results: At baseline, the mean disease duration was 9.4 ± 7.5 years; the prevalence of previous HZ infection, VTE, MACE, and cancer was respectively 4.12%, 0%, 7.21%, and 0.83%, respectively. In total, 76.3% of patients failed one or more biologics (one biological failure, 20.6%; two biological failures, 27.8%; three biological failures, 16.5%; four biological failures, 10.3%; five biological failures, 1.1%). After 3 months of FIL therapy, all clinimetric index results significantly improved from baseline, as well as after 6 months. Also, ESR and CRP significatively decreased at T3 and T6. Two cases of HZ were recorded, while no new MACE, VTE, or cancer were recorded during the observation time. Conclusion: Despite the limitations of the retrospective study and of the observational period of only 6 months, real-life data on the treatment of RA patients with FIL demonstrate that this Jak inhibitor therapy is safe in terms of CV, VTE events, and occurrence of cancer, and is also effective in a population identified as "difficult to treat" due to failure of previous b-DMARD therapy. [ABSTRACT FROM AUTHOR]

Sacha inchi (Plukenetia volubilis L.) is a well-known oleaginous plant used as food source and traditional medicine by indigenous people for a long time. This study was conducted to evaluate anti-arthritis effect of ethanol extract of Sacha inchi leaves and provide scientific evidence to develop the new anti-arthritis remedy from Sacha inchi. Rheumatoid arthritis model was established by injection of complete Freund's adjuvant into right hind footpads of mice and three doses of ethanol extract of Sacha inchi leaves (100, 200 and 300 mg/kg body weight) were used for treatment. The severity of arthritis was evaluated by measuring the ankle diameter and arthritic score, hematological and biochemical parameters (erythrocytes, leukocytes, lymphocytes, monocytes, granulocytes counts, erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor). The proand anti-inflammatory cytokines (TNF-α, INF-γ, IL-1β, IL-6, and IL-10) and the histology change of joint were also examined. All three doses of extracts significantly alleviated ankle diameter and arthritic score. Furthermore, the extracts could ameliorate the alternation of inflammatory cytokines as well histological features of CFA-induced mice. The efficacy of extract dose of 300 mg/kg body weight is comparable with reference drug (Mobic, 0.2 mg/kg body weight). This study indicates Sacha inchi leaf extract as the promising remedy for treatment of arthritis. [ABSTRACT FROM AUTHOR]