Search

Pilot tends to have a high prevalence of dyslipidemia. The present study aimed to identify key factors of pilot hyperlipidemia through thorough analysis of physical examination data, and to provide pilot-targeted health guidance to manage hyperlipidemia risks. The physical examination data of 1,253 pilot inpatients from January 2019 to June 2022, were evaluated and divided into two groups based on whether or not the pilot had hyperlipidemia. A total of three multivariate analysis models including logistic model, multilevel model and boosting propensity score were applied to find the risk factors of pilot hyperlipidemia. In the group of pilots with hyperlipidemia, four risk factors, including thrombin time, carbohydrate antigen 199, lymphocyte count and rheumatoid factor, were significantly different from pilots without hyperlipidemia, which might be positively associated with the incidence of hyperlipidemia. In future studies regarding pilots, whether hyperlipidemia is connected to abnormalities in thrombin time, carbohydrate antigen 199 and rheumatoid factor should be further explored. Based on the findings of the present study, pilot health management should be more refined and personalized, and attention should be paid to the risk factors of hyperlipidemia including diet and lifestyle. [ABSTRACT FROM AUTHOR]

Introduction: Clinical practice guidelines recommend autoimmune serological testing in patients newly diagnosed with interstitial lung disease of apparently unknown cause who may have idiopathic pulmonary fibrosis (IPF), in order to exclude connective tissue disease (CTD). Autoantibody positivity has been associated with unique patient profiles and prognosis in patients with IPF who otherwise lack a CTD diagnosis. Methods: This post-hoc analysis of patients with IPF from the Phase III ASCEND trial (NCT01366209) evaluated the association of antinuclear antibodies (ANA), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) status with baseline disease characteristics, disease progression [percent predicted forced vital capacity (%FVC), forced vital capacity (FVC) volume and progression-free survival (PFS)], and treatment outcomes with pirfenidone and placebo (%FVC, FVC and PFS). Results: Of 555 participants, 244/514 (47.5%) were ANA positive (ANA+), 83/514 (16.1%) had high ANA+ (ANA titre ≥ 1:160 or positive nucleolar- or centromere-staining patterns), 60/555 (10.8%) were RF positive (RF+) and/or anti-CCP positive (anti-CCP+) and 270/514 (52.5%) were autoantibody negative (AAb−). Baseline demographics and characteristics were generally comparable between autoantibody subgroups. Although not statistically significant, more placebo-treated participants with ANA+ or high ANA+ had a decline from baseline to Week 52 of ≥ 10% in %FVC or death (48.7% and 55.9%, respectively) or in FVC volume or death (48.7% and 47.1%, respectively) compared with the AAb− group (%FVC or death: 42.0%; FVC volume or death: 42.0%). The RF+ and/or anti-CCP+ group was similar to AAb−. No differences were observed in PFS. A treatment benefit for pirfenidone versus placebo was observed regardless of autoantibody status [PFS: ANA+ HR (95% CI): 0.56 (0.37 to 0.86), P = 0.007; AAb− HR (95% CI): 0.50 (0.32 to 0.78), P = 0.002]. Conclusion: IPF disease course did not differ by autoantibody status in ASCEND. Pirfenidone had a treatment benefit regardless of the presence of ANA. Trial Registration: ClinicalTrials.gov identifier, NCT01366209. Plain Language Summary: People with idiopathic pulmonary fibrosis sometimes have abnormal antibodies, called autoantibodies, in their blood. Uncommonly, autoantibodies may mistakenly target the person's own tissues, including the lungs. It is unknown whether these autoantibodies cause idiopathic pulmonary fibrosis or make it worse. This analysis looked at data from the ASCEND clinical trial in people with idiopathic pulmonary fibrosis, who were split randomly into two groups to receive tablets of either a medicine called pirfenidone or a placebo for 52 weeks. One goal was to see whether people with certain autoantibodies called antinuclear antibodies ('ANA' for short), rheumatoid factor ('RF') and anti-cyclic citrullinated peptide ('anti-CCP') had different traits from people without autoantibodies, such as age, race or smoking history. Other goals were to see if autoantibodies affected (1) how well people's lungs worked during the trial, (2) how quickly people's idiopathic pulmonary fibrosis got worse or they died and (3) how well pirfenidone worked. The analysis showed that most traits were similar in people with and without autoantibodies. In people who received placebo, the change in lung function during the trial was not different for people with ANA, RF or anti-CCP compared with people with no autoantibodies. People who received pirfenidone were less likely to have worsening lung function, or die, than people who received placebo, regardless of whether or not they had autoantibodies. Doctors evaluating patients with idiopathic pulmonary fibrosis should consider the impact of autoantibodies and feel confident that pirfenidone is effective regardless of whether or not autoantibodies are present. [ABSTRACT FROM AUTHOR]

Background/Objectives: The prevalence of Interstitial Lung Disease (ILD) and risk factors for its development in patients with primary Sjögren's syndrome (pSS) are still debated, possibly due to the existence of heterogeneous pSS-related ILD phenotypes. The aims of this study were: 1. To investigate the prevalence and predictive factors for ILD development in a single-center pSS cohort; 2. To characterize different pSS-ILD phenotypes. Methods: Clinical, laboratory and imaging data of pSS patients attending our center from January 2019 to September 2023 were retrospectively analyzed. ILD presence was confirmed on HRCT. Results: Forty-three out of 474 enrolled pSS patients presented ILD (M:F = 6:37), accounting for an overall ILD prevalence of 9.1%. In 19 cases, ILD was the first manifestation of pSS (ILD-onset), while in 24 ILD was diagnosed after pSS (ILD-incident). Compared to ILD-onset, ILD-incident patients more often presented pSS-related hematologic abnormalities (p = 0.012), cutaneous involvement (p = 0.027), inflammatory arthralgias (p = 0.026), C4 hypocomplementemia (p = 0.012) and positive RF (p = 0.031). On the other hand, ILD-onset patients were significantly older at pSS diagnosis (p = 0.008) and presented more severe fibrosis on HRCT (p = 0.008). On the univariate analysis, higher ESSDAI (p = 0.011), Raynaud's phenomenon (p = 0.009), anti-Ro52 (p = 0.031), hypergammaglobulinemia (p = 0.011), Rheumatoid Factor (RF) (p = 0.038) and C4 hypocomplementemia (p = 0.044) at baseline were associated to ILD development during follow-up. On the multivariate analysis, the ESSDAI at baseline (p = 0.05) and Raynaud's phenomenon (p = 0.013) at baseline were the only independent predictors of ILD development. Conclusions: ILD is a relatively common and clinically heterogenous pSS manifestation. Elevated disease activity at pSS onset is a risk factor for ILD development, prompting careful follow-up and intriguingly suggesting that immunomodulatory therapies may prevent ILD. [ABSTRACT FROM AUTHOR]

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]

The complement (C) system is implicated in the etiopathogenesis of rheumatoid arthritis (RA). However, there is a lack of studies characterizing all three C pathways in RA patients. This study aimed to evaluate the association between an in-depth examination of the C system and RA patient characteristics, focusing on disease activity and the presence of rheumatoid factor and anti-citrullinated protein autoantibodies (ACPA). In a cohort of 430 RA patients, functional assays of the three C pathways (classical, alternative, and lectin) and serum levels of their components were assessed. Components included C1q (classical); factor D and properdin (alternative); lectin (lectin); C1-inhibitor; C2, C4, and C4b (classical and lectin); C3, C3a, and C4b (common); and C5, C5a, and C9 (terminal). A multivariable linear regression analysis showed significant positive correlations between C-reactive protein and C system proteins and functional assays, especially in the terminal and common pathways. Disease activity, measured by scores with or without acute phase reactants, positively correlated with the classical pathway functional test and terminal pathway products. Conversely, rheumatoid factor or ACPA presence was associated with lower classical pathway values and decreased C3a and C4b levels, suggesting complement depletion. In conclusion, RA disease activity increases C molecules and functional complement assays, while rheumatoid factor or ACPA positivity is linked to C consumption. Our study offers a detailed analysis of the complement system's role in RA, potentially guiding the development of more targeted and effective treatment strategies. [ABSTRACT FROM AUTHOR]

Inflammatory arthritis may be the principal feature or one component of an inflammatory rheumatological disease. It is a clinical diagnosis, principally made based on the patient’s history and examination. Specific investigations, such as rheumatoid factor and human leucocyte antigen B27 gene, may support the diagnosis in the context of a suggestive clinical presentation, but a diagnosis cannot be made based on these tests alone because positive results may also be seen in healthy individuals. To reduce the likelihood of false positive results, laboratory and radiological investigations should be tailored to the suspected diagnosis based on pretest probability. While musculoskeletal symptoms are a common presentation in general practice, specific features that increase suspicion of an inflammatory arthritis include prolonged morning stiffness (more than 1 hour) that is improved by exercise or movement. A broad ‘rheumatological panel’ increases the likelihood of false positive results and should be avoided to prevent unnecessary further investigations and treatment, and unwarranted anxiety in both the patient and the doctor. [ABSTRACT FROM AUTHOR]

Background: The examination of anti-double stranded DNA (ds-DNA) IgG antibody is of great significance for the diagnosis, differential diagnosis, assessment of disease activity, and prognosis of disease recurrence in SLE. Methods: We used a chemiluminescence method to detect ds-DNA IgG and found that the levels of ds-DNA IgG antibody in the patient's serum were significantly increased and the indirect immunofluorescence (IIF) test result was negative. Laboratory tests show that the patient's RF level far exceeds the upper limit of their reference range. Results: RF 110.6 IU/mL, ds-DNA IgG 753 IU/mL; After PEG6000 treatment, the RF was 108.7 IU/mL, and then the ds-DNA IgG was measured at 23.5 IU/mL. Conclusions: The RF IgM subtype is the main cause of RF interference in IgG antibody detection, mainly due to the binding of the Fc region of RF to the Fab segment of IgG. Combining with capture antibodies and labeled antibodies leads to the formation of non-specific detection signals, or directly reacting with the detected substance, resulting in false positive test results. [ABSTRACT FROM AUTHOR]

Rheumatoid factor (RF), an established diagnostic biomarker for rheumatoid arthritis (RA), is associated with cardiovascular diseases, but its impact on clinical outcomes of ischemic stroke remains unclear. We aimed to investigate the observational associations between serum RF and prognosis of ischemic stroke, and further examined the genetic associations of RA and its therapeutic strategy, interleukin-6 (IL-6) inhibitor, with prognosis of ischemic stroke. We measured serum RF levels in 3474 Chinese ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke. The primary outcome was the composite outcome of death or major disability (modified Rankin Scale score ≥3) at 3 months after stroke onset. Mendelian randomization (MR) analyses were performed to examine the associations of genetically predicted RA and IL-6 inhibition with prognosis of ischemic stroke. During 3 months of follow-up, 866 patients (25.43%) experienced death or major disability. After multivariate adjustment, RF-positive was significantly associated with a high risk of primary outcome (OR, 1.47; 95% CI, 1.08–2.00; P =0.016) compared with RF-negative. The two-sample MR analyses suggested that genetically predicted RA was associated with an increased risk of primary outcome (OR, 1.09; 95% CI, 1.01–1.18; P=0.021), while genetically predicted IL-6 inhibition was associated with a decreased risk of primary outcome (OR, 0.88; 95% CI, 0.77–0.99; P=0.041). We found that positive RF was associated with increased risks of adverse outcomes after atherosclerotic ischemic stroke, and genetically predicted RA and IL-6 inhibition increased and decreased the risks of adverse outcomes after ischemic stroke, respectively. [ABSTRACT FROM AUTHOR]

Abstract\nHIGHLIGHTSObjectiveThis study aimed to evaluate prevalence rates (PRs) of neurocognitive impairment and its potential moderators among patients with rheumatoid arthritis (RA). MethodA systematic review of the available literature and data extraction was undertaken on 6 August 2021, with the update by 14 September 2023, by two reviewers independently. Literature was screened for reported rates of prevalence of neurocognitive impairment in RA patients. The meta-analysis was performed using RStudio with the “meta” library. ResultsTwenty-two studies that fulfilled all selection criteria were carefully analyzed. The PR of neurocognitive impairment was 0.49 [0.38–0.61] across all studies included in the review; 0.75 [0.54–0.88] for the MoCA; 0.56 [0.40–0.72] for the MMSE; and 0.26 [0.16–0.38] for comprehensive batteries. The meta-regression results indicated that, depending on the measurement method, the percentage of subjects with positive rheumatoid factor, women ratio, mean age of participants, mean duration of RA, and percentage of domains that had to be impaired to diagnose neurocognitive impairment turned out to be statistically significant moderators. ConclusionsNeurocognitive impairment is a clinically relevant condition in many RA patients, and its prevalence is alarming high.Rheumatoid arthritis (RA) is a chronic systemic disease that has a significant negative impact on functioning. Difficulties experienced by RA patients described in the literature may involve various organs and systems, including the central nervous system. The results obtained in the review indicate that cognitive impairment may affect, depending on the measurement method, up to approximately 75% of the patients. Due to potential limitations related to cognitive dysfunctions, such as reduced compliance or difficulties in everyday functioning, such a high prevalence of neurocognitive dysfunctions is an argument for screening RA patients and developing appropriate support methods. [ABSTRACT FROM AUTHOR]

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]

Aim of the study was to investigate the demographic data and disease course characteristics of patients with Sjögren's syndrome (SS) and inflammatory joint pain of various origins and to search for factors that might help with the distinction of polyarthritis as an extraglandular manifestation and rheumatoid arthritis as an associated systemic autoimmune disorder. A total of 355 patients were retrospectively analyzed, 128 of whom served as controls (SS-C), while 159 had polyarthritis as an extraglandular symptom of Sjögren's syndrome (SS-pa) and 68 were diagnosed as having associated rheumatoid arthritis (SS-RA). The patients without any inflammatory joint manifestations were significantly older than the SS-pa patients, while, for the SS-RA group, the difference was not significant. The onset of joint pain appeared significantly earlier in the SS-RA patients. Regarding either extraglandular manifestations or associated autoimmune disorders, there were significant differences between the controls and both SS-pa and SS-RA groups, while no significant difference was found between the SS-pa and SS-RA groups. Thus, laboratory and imaging methods should be used to differentiate between the two conditions, but laboratory biomarkers are even more important for early diagnosis. A ROC curve analysis showed an acceptable diagnostic accuracy in differentiating between SS-pa and SS-RA patients using a binary logistic regression model, where highly positive rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) values, kidney involvement, and anti-Ro/SS-A positivity were shown to significantly raise the odds of having RA, whereas anti-La/SS-B positivity seemed to have a protective role, since it significantly decreased the odds of having it. Further biomarkers are needed to better classify SS patient cohorts with inflammatory joint pain of different origins and, consequently, different management requirements. [ABSTRACT FROM AUTHOR]

ObjectiveMethodResultsConclusionsTo investigate and compare trends in incidence rates (IRs) of seropositive and seronegative rheumatoid arthritis (RA) in Denmark using various data sources for serostatus definition.This nationwide population-based cohort study was based on data from Danish healthcare and clinical quality registries between 2000 and 2018. Information on anti-cyclic citrullinated peptide and immunoglobulin M rheumatoid factor was obtained, and definitions of seropositivity according to the number of applied data sources were prespecified. Annual age- and sex-standardized IRs were calculated as the number of incident seropositive and seronegative cases, divided by the number of person-years (PY) in the general population in that given year.An increasing temporal trend in IR of seropositive RA and a decreasing trend in seronegative RA were observed. The IRs were higher for seropositive RA than for seronegative RA from 2009 onwards, with a widening of the IR gap between 2009 and 2016 regardless of the definition of seropositivity. When combining laboratory- and physician-reported autoantibody information and ICD-10 codes, the IR of seropositive RA in 2018 was approximately twice that of seronegative RA, at 19.0 and 9.0 per 100 000 PY, respectively. The level of antibody testing increased significantly during the study period.The IR of seropositive RA increased over time, whereas the IR of seronegative RA decreased. Temporal IR changes may be caused by a real change in the RA serology subtypes, an increase in autoantibody testing and availability, changes in registration practice over time, or a combination of these factors. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, attributed in part to myocardial dysfunction. Global longitudinal strain (GLS) measured by speckle-tracking echocardiography is a sensitive marker of myocardial function. This study aimed to investigate the association between RA serology markers, including rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, and GLS in RA patients. Materials and Methods: This one-year cross-sectional study was conducted at Imam Hossein Hospital in Tehran, Iran, focusing on patients diagnosed with RA. Rheumatoid arthritis serology markers, including RF and anti-CCP antibodies, were assessed. GLS was measured using speckle-tracking echocardiography. The association between RA serology markers and GLS categories was analyzed using chi-square tests with IBM SPSS Statistics version 26. Results: A total of 71 patients were included in the study, with a mean age of 52.31 years. Among the RA patients, 28 individuals (71.8%) with negative RA serology exhibited abnormal GLS values, while 11 (28.2%) had normal GLS values. Conversely, all 21 (100%) RA patients with positive serology showed abnormal GLS values. Statistical analysis revealed no significant association between RA serology markers and GLS category (χ2 = 0.313, P>0.05). Conclusion: In this study, RA serology markers, including RF and anti-CCP antibodies, were not significantly associated with GLS abnormalities in RA patients. Further research is needed to elucidate other factors contributing to myocardial dysfunction in RA. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease indicated by joint inflammation and cartilage destruction. Matrix metalloproteinase (MMP) enzymes play an influential role in inflammation by affecting the invasion and degradation of anatomical barriers. In this way, the current study investigated the relationship between the MMP-9-1562C/T gene polymorphism and this enzyme's serum level in RA. The serum levels of MMP-9 in RA patients and healthy controls were measured using the enzyme-linked immunosorbent assay (ELISA). RA was confirmed using rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and C-reactive protein (CRP). Then the MMP-9-1562C/T gene polymorphism was analyzed utilizing polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Also, multivariate analysis investigated the connection between this polymorphism and the risk of RA. In this study, the increase of MMP-9 in patients due to the development of single nucleotide polymorphism in the promoter region of this gene (−1562 C→T) was confirmed by increasing the frequency of heterozygous genotype (CT). Logistic regression analysis also demonstrated that the chance of development of RA is higher in people with CT/CC genotype than in other alleles. We demonstrated that MMP-9-1562C/T gene polymorphism can play a significant role in the occurrence of RA. [ABSTRACT FROM AUTHOR]

This study aimed to estimate the prevalence of cryptococcal antigenemia detected by lateral flow assay (LFA) in AIDS patients and its accuracy in the diagnosis of cryptococcosis. Conducted at a university hospital in Brazil from March 2015 to July 2017, it included AIDS patients over 18 years old with a CD4+ count ≤ 200 cells/mm3. Cryptococcal antigen (CrAg) detection using LFA and latex agglutination (LA), along with blood and urine cultures, were performed. The reference standard was the identification of Cryptococcus spp. in clinical specimens through microbiological or histopathological examination. Among 230 patients, the prevalence of CrAg detected by LFA (CrAg LFA) was 13.0%. Factors associated with cryptococcal antigenemia included fever, vomiting, seizures, and a lack of antiretroviral therapy. The sensitivity and specificity of CrAg LFA were 83.9% and 98.0%, respectively. The positive predictive value (PPV) was 86.7%, the negative predictive value (NPV) was 97.5%, and overall accuracy was 96.1%. Cross-reactions were observed in patients with histoplasmosis and paracoccidioidmycosis, but not with aspergillosis or positive rheumatoid factor. The study concludes that the LFA is a useful tool for detecting cryptococcal antigenemia in severely immunocompromised AIDS patients due to its high NPV, specificity, and PPV. [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 Hashimoto's thyroiditis (HT) is an autoimmune disease that is frequently associated with other autoimmune conditions. Objective To perform serological screening for rheumatoid arthritis (RA) in patients with HT. Methods Our study included 88 consecutive serum specimens of patients with confirmed HT and 88 sex- and age-matched healthy subjects. All study participants were tested for anti-cyclic citrullinated peptides antibodies (CCP-Ab) and rheumatoid factor (RF). CCP-Ab and RF were performed using ELISA commercial kits. Statistical analysis was conducted using Epi Info, version 3. Results Out of 88 patients with HT, 15 (17.0%) had CCP-Ab or RF. The frequency of serological markers of RA was significantly higher in patients than in control individuals (17.0% vs 4.5%; P =.007). RF was more frequent in patients than in the control group, and the difference was statistically significant (13.6% vs 3.4%; P =.01). Isolated RF-IgM was absent in all controls and present in 6 patients with HT (6.8% vs 0%; P =.02). Out of 14 male patients, 3 (21.4%) had antibodies of RA. There was no significant difference in age between patients with CCP-Ab or RF and those without. Conclusion A high frequency of serological markers of RA was highlighted in patients with HT. [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]

The diagnosis and treatment of Sjogren's syndrome (SS) are commonly conducted by rheumatologists and stomatologists. The purpose of this study was to compare the scientometric characteristics of SS publications by rheumatologists and stomatologists. All the papers on cheilitis were comprehensively retrieved from the Scopus database, and divided into rheumatologists and stomatologists groups. There were 3245 and 1209 papers on SS were published by rheumatologists and stomatologists, respectively. For the most-cited top-200 papers, the total citation count was 29,764 and the h index was 108 for SS publications by rheumatologists; whereas the count is 19,891 and h index is 81 for publications by stomatologists. Interestingly, we observed that accumulated citations of the publications by stomatologists cooperated with rheumatologists were larger than those by stomatologists alone during 2012–2022. The more common keywords such as saliva, salivation, minor salivary glands, parotid gland, submandibular gland, sialography, lip, dental caries, and hyposalivation were reported by stomatologists. The more frequent keywords such as rheumatoid factor, fatigue, lymphoma, interstitial lung disease, arthralgia, Raynaud phenomenon, lymphadenopathy, and vasculitis were reported by rheumatologists. This study firstly reports the scientometric characteristics of SS publications by rheumatologists and stomatologists. The scale and citations of rheumatologists' publications greatly outweigh those of stomatologists, suggesting stomatologists can cooperate more with rheumatologists regarding SS research. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Contemporary Pediatrics is the property of Xiangya Medical Periodical Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Rim Sghiri,1,&ast; Hana Ben Hassine,2,&ast; Mariam Ghozzi,2 Nejla El Amri,3 Khadija Baccouche,3 Rihab Sarraj,3 Zahid Shakoor,1 Adel Almogren,1 Elyes Bouajina3 1Immunology Unit, Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Immunology Laboratory, Farhat Hached Hospital, Sousse, Tunisia; 3Department of Rheumatology, Farhat Hached Hospital, Sousse, Tunisia&ast;These authors contributed equally to this workCorrespondence: Rim Sghiri, Immunology Unit, Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia, Email rimsghiri2023@gmail.comPurpose: FRAX® is a tool used for evaluation of risk of fracture in RA and non-RA patients and to identify those eligible for intervention. One of the limitations of FRAX in RA settings is that it does not consider factors known to contribute to osteoporosis such as autoantibodies. This study analysed the association of anti-mutated citrullinated vimentin antibody (anti-MCV), anti-cyclic citrullinated peptide antibody (anti-CCP), IgM rheumatoid factor (RF), IgA RF with 10-year risk of major osteoporosis and hip fracture.Methods: FRAX® tool was used to estimate 10-year risk of major osteoporosis fracture and hip fracture in 189 RA patients over 40 years of age. Anti-MCV, anti-CCP, IgM RF and IgA RF were tested using enzyme immunoassay and analysed at different levels. Results were adjusted for various confounders including disease activity.Results: Fifty-one (26.9%) RA patients had high (≥ 20%) 10-year risk of major osteoporosis fracture and 67 (35.4%) had high (> 3%) 10-year risk of hip fracture. Among all the tested autoantibodies, only IgM RF at elevated levels was associated with high 10-year risk of major osteoporosis fracture (adjusted OR = 4.1, 95% CI = 1.5– 11.3, p = 0.006) and of hip fracture (adjusted OR = 17.4, 95% CI = 3.7– 81.3, p < 0.0001). There was no agreement between FRAX and femoral neck (FN) BMD. None of the autoantibodies tested were associated with FN osteopenia or osteoporosis including IgM RF at high levels.Conclusion: Our study highlights the importance of quantitative measurement of autoantibodies in assessment of risk for fractures among RA patients. Our preliminary findings need to be assessed in prospective studies to determine the actual predictive value of high IgM RF levels among patients with RA.Keywords: osteoporosis, rheumatoid arthritis, 10-years risk of major osteoporosis fracture, 10-years risk of hip fracture, FRAX, anti-mutated citrullinated vimentin antibody, anti-cyclic citrullinated peptide antibody, rheumatoid factor, rheumatoid factor isotypes

Background: Rheumatoid arthritis (RA) is a chronic immune system disease with a high disability rate threatening the living quality of patients. Identifying potential biomarkers for RA is of necessity to improve the prevention and management of RA. Objectives: This study focused on miR-146b-3p evaluating its clinical significance and revealing the underlying regulatory mechanisms. Materials and methods: A total of 107 RA patients were enrolled, and both serum and synovial tissues were collected. Another 78 osteoarthritis patients (OA, providing synovial tissues), and 72 healthy individuals (providing serum samples) were enrolled as the control group. The expression of miR-146b-3p was analyzed by PCR and analyzed with ROC and Pearson correlation analyses evaluating its significance in diagnosis and development prediction of RA patients. In vitro, MH7A cells were treated with TNF-α. The regulation of cell proliferation, motility, and inflammation by miR-146b-3p was assessed by CCK8, Transwell, and ELISA assays. Results: Significant upregulation of miR-146b-3p was observed in serum and synovial tissues of RA patients, which distinguished RA patients and were positively correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP), and rheumatoid factor (RF) of RA patients. TNF-α promoted the proliferation and motility of MH7A cells and induced significant inflammation in cells. Silencing miR-146b-3p alleviated the effect of TNF-α and negatively regulated the expression of HMGCR. The knockdown of HMGCR reversed the protective effect of miR-146b-3p silencing on TNF-α-stimulated MH7A cells. Conclusions: Increased miR-146b-3p served as a biomarker for the diagnosis and severity of RA. Silencing miR-146b-3p could suppress TNF-α-induced excessive proliferation, motility, and inflammation via regulating HMGCR in MH7A cells. [ABSTRACT FROM AUTHOR]

Background: Lung ultrasound (LUS) is a tool of growing interest in Rheumatoid Arthritis (RA) oligo- symptomatic ILD to avoid. Objective: We aimed to evaluate (i) the prevalence of pleural (PLUS) and parenchymal (PAUS) abnormalities in LUS in the RA population and their possible correlation to biomarkers; (ii) the predictivity of gender, smoking habits, previous infections (past COVID-19 tuberculosis), and treatments; (iii) the differences in LUS between sexes. Methods: We collected the data of 155 (15 early and 140 late) RA patients with mild respiratory symptoms, evaluating PLUS and PAUS, in fourteen lung areas and also summing the scores (LUS-T). Results: Only 13/155 (8.4%) were completely negative; LUS correlated to age (all parameters p 0.0001), rheumatoid factor IgM (PLUS p 0.0006, PAUS p 0.02, LUS-T p 0.001) and ACPA (p 0.001, 0.006, 0.001, respectively), and PLUS also correlated to IL6 (p 0.02). The male gender was predictive of all LUS evaluations (p 0.001, 0.05, 0.001, respectively), which were higher than in women (p 0.001, 0.01, 0.001, respectively). Other potential risk factors were independent, except biological treatments, which showed a low predictivity to PLUS (p < 0.05). Conclusions: We can conclude that LUS is a useful technique in RA low respiratory symptoms and correlates with age, the most important RA biomarkers, and male sex. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a major contributor to global morbidity and mortality, affecting millions each year. Notwithstanding the decline in sepsis incidence and mortality over decades, gender disparities in sepsis outcomes persist, with research suggesting higher mortality rates in males. Methods: This retrospective study aims to delineate gender-specific clinical biomarker profiles impacting sepsis progression and mortality by examining sepsis cases and related clinical data from the past three years. Propensity score matching was used to select age-matched healthy controls for comparison. Results: Among 265 sepsis patients, a significantly higher proportion were male (60.8%, P<0.001). While mortality did not significantly differ by gender, deceased patients were significantly older (mean 69 vs 43 years, P=0.003), more likely to have hypertension (54% vs 25%, P=0.019), and had higher SOFA scores (mean ~10 vs 4, P<0.01) compared to survivors. Principal Component Analysis (PCA) showed clear separation between sepsis patients and healthy controls. 48 serum biomarkers were significantly altered in sepsis, with Triiodothyronine, Apolipoprotein A, and Serum cystatin C having the highest diagnostic value by ROC analysis. Genderstratified comparisons identified male-specific (e.g. AFP, HDLC) and femalespecific (e.g. Rheumatoid factor, Interleukin-6) diagnostic biomarkers. Deceased patients significantly differed from survivors, with 22 differentially expressed markers; Antithrombin, Prealbumin, HDL cholesterol, Urea nitrogen and Hydroxybutyrate had the highest diagnostic efficiency for mortality. Conclusion: These findings enhance our understanding of gender disparities in sepsis and may guide future therapeutic strategies. Further research is warranted to validate these biomarker profiles and investigate the molecular mechanisms underlying these gender differences in sepsis outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Polyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite the crucial role of monocytes in arthritis, the precise involvement of classical monocytes in the pathogenesis of pJIA remains uncertain. Here, we aimed to uncover the transcriptomic patterns of classical monocytes in pJIA, focusing on their involvement in disease mechanism and heterogeneity. Methods: A total of 17 healthy subjects and 18 premenopausal women with pJIA according to ILAR criteria were included. Classical monocytes were isolated, and RNA sequencing was performed. Differential expression analysis was used to compare pJIA patients and healthy control group. Differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was performed. Using unsupervised learning approach, patients were clustered in two groups based on their similarities at transcriptomic level. Subsequently, these clusters underwent a comparative analysis to reveal differences at the transcriptomic level. Results: We identified 440 DEGs in pJIA patients of which 360 were upregulated and 80 downregulated. GSEA highlighted TNF-α and IFN-γ response. Importantly, this analysis not only detected genes targeted by pJIA therapy but also identified new modulators of immuno-inflammation. PLAUR, IL1B, IL6, CDKN1A, PIM1, and ICAM1 were pointed as drivers of chronic hyperinflammation. Unsupervised learning approach revealed two clusters within pJIA, each exhibiting varying inflammation levels. Conclusion: These findings indicate the pivotal role of immuno-inflammation driven by classical monocytes in pJIA and reveals the existence of two subclusters within pJIA, regardless the positivity of rheumatoid factor and anti-CCP, paving the way to precision medicine. [ABSTRACT FROM AUTHOR]

Background and aims: Thyroid function abnormalities and thyroid autoantibodies have previously been described in rheumatoid arthirits (RA) with limited data. In some studies, a relationship was found between thyroid autoantibodies and RA disease activity. However, there are not strong studies in the literature indicating the relationship between thyroid diseases and RA. The aim of this study was to determine the frequency of hypothyroidism and to investigate the relationship between thyroid hormone levels, autoantibodies and disease activity in patients with rheumatoid arthritis (RA). Methods: 1017 patients with the diagnosis of RA were recruited. This observational study was conducted between January 2014 and July 2015. Demographic variables were recorded. Anti-nuclear antibodies (ANA), anti-cyclic citrulli-nated peptide antibody (anti-CCP), Rheumatoid Factor (RF), C reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), anti-microsomal antibody (anti-TPO)and anti-thyroglobulin antibody (anti-TG) were determined. Visual analog score and Disease Activiy Score 28 (DAS-28) ESR and DAS-28 CRP were recorded. The relationship between thyroid hormone levels and thyroid antibodies and disease activity parameters were determined. Results: 98 (%9,7) patients had hypothyroidism and 61 (%6) patients had hyperthyroidism. 210 (20,7%) patients with RA was positive for TPOAb and 165(16,3%) for anti-TG. Positive correlation was detected between anti-TPO positivity and anti-CCP levels (p:0.005, r:0,274). In anti-TG antibody positive patients, there was a significant positive correlation of thyroid hormone levels with CRP and DAS 28-CRP (p:0.01, r:0,120; p:0.01, r:0,169). Conclusion: Thyroid autoantibodies were found to be positive in 16-21% of patients with RA. Though hypothyroidism is not very frequent in RA patients, autoimmune thyroid disease is quite common, which may be related to disease activity. [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]

Objective: Seronegative rheumatoid arthritis (RA) is defined as RA without circulating autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies; thus, early diagnosis of seronegative RA can be challenging. Here, we aimed to identify diagnostic biomarkers for seronegative RA by performing lipidomic analyses of sera and urine samples from patients with RA. Methods: We performed untargeted lipidomic analysis of sera and urine samples from 111 RA patients, 45 osteoarthritis (OA) patients, and 25 healthy controls (HC). These samples were divided into a discovery cohort (n = 97) and a validation cohort (n = 84). Serum samples from 20 patients with systemic lupus erythematosus (SLE) were also used for validation. Results: The serum lipidome profile of RA was distinguishable from that of OA and HC. We identified a panel of ten serum lipids and three urine lipids in the discovery cohort that showed the most significant differences. These were deemed potential lipid biomarker candidates for RA. The serum lipid panel was tested using a validation cohort; the results revealed an accuracy of 79%, a sensitivity of 71%, and a specificity of 86%. Both seropositive and seronegative RA patients were differentiated from patients with OA, SLE, and HC. Three urinary lipids showing differential expression between RA from HC were identified with an accuracy of 84%, but they failed to differentiate RA from OA. There were five lipid pathways that differed between seronegative and seropositive RA. Conclusion: Here, we identified a panel of ten serum lipids as potential biomarkers that can differentiate RA from OA and SLE, regardless of seropositivity. In addition, three urinary lipids had diagnostic utility for differentiating RA from HC. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to identify predictors of remission or low disease activity (LDA) in patients with rheumatoid arthritis (RA) and low-ultrasound inflammation. Methods: A total of 80 patients with RA who fulfilled the 1987 ACR criteria for RA with a disease activity score of 28 joints (DAS28) > 3.2 were recruited. Over 1 year of therapy, we conducted blood tests every 6 months to examine erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), neuraminidase 3 (Neu3), and α-2,3-sialyltrasnferse I (ST3Gal-1) levels in B cells and monocytes. Additionally, we evaluated physical function by using the Health Assessment Questionnaire–Disability Index (HAQ-DI). Data on demographic and clinical parameters were collected, and musculoskeletal ultrasonography was performed twice a year on 12 specific joints to assess synovial changes. One year later, we compared all collected data and laboratory or ultrasound results between patients achieving remission or LDA and those who did not in order to determine the predictors. Results: Age, the presence or absence of rheumatoid factor, and the number of conventional disease-modifying anti-rheumatic drugs used were not correlated with remission or LDA for DAS28 or Simplified Disease Activity Index formulas. However, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores were associated with a higher likelihood of achieving remission or LDA for DAS28-ESR. Negative anticyclic citrullinated peptide (CCP) and low HAQ-DI scores were predictors of remission or LDA for DAS28-MCP-1. Interestingly, having less than two comorbidities is a good predictor of a combined remission/low disease activity state for SDAI and DAS28-MCP-1. Furthermore, Neu3 and ST3Gal-1 levels and ST3Gal-1/Neu3 ratios in B cells and monocytes had no significant correlation with total ultrasound scores. Nevertheless, monocyte ST3Gal-1 and Neu3 correlated significantly with DAS28-ESR >5.1 and DAS-MCP-1 >4.8 (both categories belong to high disease activity), respectively (rho = 0.609 with p = 0.012, and rho = 0.727 with p = 0.011, respectively). Monocyte ST3Gal-1/Neu3 ratios connected with DAS28-ESR >5.1 and 3.3 < SDAI ≦ 11 (low disease activity), respectively (rho = 0.662 with p = 0.005, and rho = 0.342 with p = 0.048, respectively). Conclusions: In patients with RA in Taiwan, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores are predictors of remission or LDA for DAS28-ESR, which differ from the predictors for DAS28-MCP-1. Moreover, monocyte ST3Gal-1, Neu3, and their ratios correlated with different disease activity categories of DAS28-ESR, DAS28-MCP-1, and SDAI scores. [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]

Background: Synovial angiogenesis and inflammation with articular damage are the main pathologic changes in rheumatoid arthritis (RA). The implication of the chemokine CXCL12 in disorders of the immune system had been identified. CXCL12 is involved in the inflammatory process by triggering leukocyte recruitment and neovascularization. Therefore, this research aims to investigate the serum CXCL12 level in RA patients and define how it correlates with disease activity. Methods: This study comprised 44 RA patients as well as 44 matched controls. Health assessment questionnaire disability index (HAQ- DI) as well as disease activity score (DAS-28) were determined. CXCL12 level was assessed in the sera of participants. Results: Serum CXCL12 concentration was significantly elevated in RA patients (1475.16 ± 480.78 pg/ml) compared to controls (484.6 ± 177.85 pg/ml; p<0.001). Significant relations were detected between CXCL12 with tender joint count (p<0.001), swollen joint count (p<0.001), morning stiffness duration (p<0.001), DAS-28 (p<0.001), HAQ-DI (p<0.001), rheumatoid factor (RF) titer (p<0.001), anti-cyclic citrullinated peptide (anti-CCP) level (p=0.001), C-reactive protein (p<0.001), and erythrocyte sedimentation rate (p<0.001). Serum CXCL12 significantly discriminated RA patients from healthy subjects (AUC = 0.99; p<0.001), as well as active RA cases from those in remission (AUC = 0.96; p<0.001). Conclusion: This study indicated the fundamental utility of serum CXCL12 in RA activity monitoring. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Background: Arthritis is an umbrella term that refers to approx 200 rheumatic diseases and conditions that affect various joints of the body, which including lupus and rheumatoid arthritis. Rheumatoid arthritis (RA) is a chronic autoimmune and common systemic inflammatory disease that results in joint deformity and functional disability when not properly managed. The early diagnosis and treatment of RA are imperative for optimal disease management, a greater probability of remission, and prevention of permanent clinical and radiographic damage. Objectives: The present study was conducted to study the value of rheumatoid factor (RF), anticyclic citrullinated peptide autoantibodies (anti-CCP), and anti-RA33 autoantibodies for diagnosis of RA and prediction of outcome in patients with very early arthritis. Methods: This was a prospective study carried out in a tertiary care centre situated at western part of India which included 30 patients aged between 18 - 65 years who presented with multiple joints pain. Inclusion criteria included Population aged between 18 to 65 years with clinically suspected patients of Rheumatoid Arthritis and Duration of signs and symptoms more than 6 weeks. Exclusion criteria included Patients <18 years and >65 years, patients with other chronic diseases such as Carcinoma, Diabetes mellitus, HIV, etc. A p-value of <0.05 was considered statistically significant. Results: Out of 30 patients, 57% of patients were females and rest 43% males. Out of which 66.66% patients were positive for antibodies and 33.33% were negative. Rheumatoid arthritis positivity was seen in 60% cases while other arthropathies were observed in 40% of cases. Specific antibody wise distribution shows 75% positivity with RF - IgM plus ACPA (Anticitrulline protein antibody) and 25% positivity with RA - 33 antibody. Conclusion: LIA based autoantibody testing in early inflammatory joint disease, should be used as a sensitive and effective strategy for distinguishing patients with RA at high risk for poor outcome. Anti - CCP is an extremely helpful diagnostic marker being not only highly specific for RA but also strongly associated with erosive disease. [ABSTRACT FROM AUTHOR]

Introduction: Subjects with autoantibody rheumatoid factor (RF) have strong association with Rheumatoid Arthritis (RA) and have an increased prevalence of Ischemic Heart Disease (IHD). Presence of RF in general population may also share an increased likelihood of developing IHD and that RF may have a special role in the pathogenesis of IHD. Objective: To analyse RF as an independent and additional risk factor for IHD in general population. Methods: A cross sectional observational study was conducted on fifty patients with rheumatoid arthritis with RF positive status, attending S.S Hospital, Davangere during the study period and evaluated for IHD by ECG. All subjects included in the study had been explained about the procedure and valid informed written consent was taken. Those who are included in the study were also evaluated for traditional risk factors like h/o Diabetes, smoking (in the past / present), family h/o IHD and were clinically examined for Hypertension, BMI for Obesity and features of RA. Results: Among 50 patients with RF positivity, 18 (36%) were males and 32 (64%) were females. 8 patients had ischemic changes in ECG, out of which, 6 (75%) were males and 2 (25%) were females. Among 8 patients with ischemic changes, 6 patients had traditional risk factors, 4 were males (75%) and 2 were females (25%). In addition, 2 patients without traditional risk factors had ischemic changes and both of them were males. Conclusion: RF per se can be considered as an independent risk factor for IHD in men and if associated with traditional risk factors, it increases the prevalence of IHD. However, more female patients have RF positivity, they are not vulnerable to IHD. [ABSTRACT FROM AUTHOR]

Introduction: Identifying early predictive factors of how rheumatoid arthritis (RA) patients respond to rituximab (RTX) treatment is crucial for both individual treatment outcome and the improvement of clinical practice overall. This study aimed to identify early predictive factors available in standard clinical practice for predicting RTX treatment outcomes in RA patients. Material and methods: Data on seventy patients diagnosed with RA treated with RTX (two 1,000 mg doses 2 weeks apart or two 500 mg doses 2 weeks apart) were retrospectively collected. Baseline information collected at the initiation of RTX treatment included patient characteristics such as age, sex, disease duration, disease activity, Health Assessment Questionnaire score, erythrocyte sedimentation rate, C-reactive protein, and serological status regarding rheumatoid factor (RF) and anti-cyclic citrullinated protein antibodies (ACPA). Clinical responses were analyzed 6 months after RTX initiation using the European Alliance of Associations for Rheumatology criteria. Potential predictors associated with positive RTX response at 6 months were identified using a multivariate ordinal logistic regression model. Results: The analysis showed that persistently active RA disease, Disease Activity Score with 28-joint count (DAS28) values at the treatment onset and after 3 months, along with erythrocyte sedimentation rate at treatment initiation, were negatively correlated with the response to RTX therapy (p < 0.05). All these correlations were statistically significant at the 99% confidence interval. The correlation and logistic regression analyses indicate that there are no significant association between RF and ACPA concerning therapy response, despite a higher number of RTX responders in the seropositive groups. Additionally, the study emphasizes the prognostic significance of the DAS28 value at treatment initiation in predicting therapy response at 6 months. Conclusions: The optimal model for predicting RTX response at 6 months involves the interaction of all clinical factors examined in this study, as revealed by the analysis of multiple variables. [ABSTRACT FROM AUTHOR]

Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical features of and immunological factors in RA pathogenesis could be linked to the NO lung dynamics in early disease. A total of 44 patients with early RA and anti-citrullinated peptide antibodies (ACPAs), specified as cyclic citrullinated peptide 2 (CCP2), were included. Their exhaled NO levels were measured, and the alveolar concentration, the airway compartment diffusing capacity and the airway wall concentration of NO were estimated using the Högman–Meriläinen algorithm. The disease activity was measured using the Disease Activity Score for 28 joints. Serum samples were analysed for anti-CCP2, rheumatoid factor, free secretory component, secretory component containing ACPAs, antibodies against Porphyromonas gingivalis (Rgp) and total levels of IgA, IgA1 and IgA2. Significant negative correlations were found between the airway wall concentration of NO and the number of swollen joints (Rho −0.48, p = 0.004), between the airway wall concentration of NO and IgA rheumatoid factor (Rho −0.41, p = 0.017), between the alveolar concentration and free secretory component (Rho −0.35, p = 0.023) and between the alveolar concentration and C-reactive protein (Rho −0.36, p = 0.016), but none were found for anti-CCP2, IgM rheumatoid factor or the anti-Rgp levels. In conclusion, altered NO levels, particularly its production in the airway walls, may have a role in the pathogenesis of ACPA-positive RA. [ABSTRACT FROM AUTHOR]

Objectives: Nephritis is a life-threatening complication of primary Sjögren's syndrome (pSS), with membranous nephropathy (MN) being prevalent. Renal biopsy is the gold standard for MN diagnosis, but it is invasive and cannot be repeatedly performed. This study aimed to develop a nomogram for the prediction of MN in patients with pSS. Methods: This retrospective study included patients with pSS admitted to the Rheumatology and Immunology Department of the First Affiliated Hospital of China Medical University between January 2015 and January 2021. A nomogram was developed using multivariable logistic regression analysis and evaluated using receiver operating characteristic (ROC) curve analysis. Bootstrap resampling analysis (1,000 times) was performed to evaluate the nomogram for discrimination and the calibration curve for consistency. Results: A total of 237 patients with pSS [aged 53.00 (44.00, 61.00) years] were included, with 35 pSS-MN patients. Based on clinical practice and multivariable logistic regression analysis, seven variables associated with pSS-MN were selected, including white blood cells, creatine, complement 3, rheumatoid factor, antinuclear antibodies, anti-SSA antibody, and interstitial lung disease. The area under the ROC curve was 0.860 (95% confidence interval: 0.796-0.919), indicating good predictive power. In addition, the nomogram exhibited excellent performance, as demonstrated by the calibration curve and decision curve analysis. Conclusion: This study developed a risk prediction nomogram for MN in patients with pSS, with high predictive power. It may be used to improve the management of patients with pSS. [ABSTRACT FROM AUTHOR]

Background: Human leukocyte antigen (HLA-G) plays a role in inflammation and autoimmune disorders. Variations in the HLA-G gene may have an effect on rheumatoid arthritis (RA). This study examined the impact of the polymorphisms +3142G>C and 14 bp ins/del on disease susceptibility, activity, severity, and responsiveness to therapy in a cohort of Egyptian RA patients. Methods: This case-control study was done on 75 patients with RA and 75 healthy people. The HLA-G rs1063320 (+3142G>C) and rs66554220 14 bp insertion (ins)/deletion (del) variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFP) and PCR technique, respectively. Results: Our finding didn't support an association between HLA-G 14 bp ins/del or the HLA-G +3142G>C variants and RA susceptibility. Subcutaneous nodules and prolonged morning stiffness were substantially related with the G allele of HLA-G +3142G>C. We used the disease activity score 28 (DAS-28) to look for a correlation between the HLA-G gene variations and disease activity, but we were unable to find one. Higher levels of C-reactive protein (CRP) and autoantibodies (anti-citrullinated protein antibodies (ACPA) and ACPA+ rheumatoid factor (RF)) have been linked to the GG genotype and the G allele of HLA-G +3142G>C. Higher rheumatoid arthritis severity scale (RASS) was found to be related to the HLAG+3142G>C polymorphism and RA severity. The 14 bp ins/del polymorphism and treatment response were found to be significantly correlated. Patients with the del/del genotype and the del allele had a significantly higher percentage of satisfactory response to therapy. Conclusion: The 14 bp ins/del and the +3142G>C of HLA-G gene didn’t appear to be associated with RA susceptibility in this studied group of RA patients. But in terms of autoantibody production, severity, clinical phenotype, and treatment responsiveness, it may operate as a genetic modulator of disease phenotype. In this regard, we propose that rather than serving as a risk factor for the onset of RA, these polymorphisms serve as disease modifiers. Treatment response and polymorphism were discovered. Patients with the del/del genotype and the del allele had a significantly higher percentage of satisfactory response to therapy [ABSTRACT FROM AUTHOR]

Rheumatoid factor (RF) is an autoantibody against IgG that affects autoimmune diseases and inhibits the effectiveness of pharmaceuticals and diagnostic agents. Although RFs derived from various germline genes have been identified, little is known about their molecular recognition mechanisms. In this study, the Fv-clasp format was used to prepare YES8c, an RF. We developed an Escherichia coli secretion expression system capable of producing milligram-scale of YES8c Fv-clasp per 1 L of culture. Although YES8c is an autoantibody with very low affinity, the produced Fv-clasp maintained specific binding to IgG. Interestingly, the molecules prepared by E. coli secretion had a higher affinity than those prepared by refolding. In the structure of the YES8c–Fc complex, the N-terminus of the light chain is close to Fc; therefore, it is suggested that the addition of the N-terminal methionine may cause collisions with Fc, resulting in reduced affinity. Our findings suggest that the Fv-clasp, which provides sufficient stability and a high bacterial yield, is a useful format for studying RFs with very low affinity. Furthermore, the Fv-clasp produced from a secretion expression system, which can properly process the N-terminus, would be suitable for analysis of RFs in which the N-terminus may be involved in interactions. [ABSTRACT FROM AUTHOR]

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]

The article discusses the crucial role of laboratory diagnostics in diagnosing and assessing the progression of inflammatory rheumatic diseases, emphasizing the necessity of interpreting lab results within a clinical context. It covers key aspects of major rheumatological conditions, highlighting the selection and interpretation of significant laboratory parameters such as C-reactive protein and Rheumatoid Factor in diseases like rheumatoid arthritis and polymyalgia rheumatica.

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]

Background: The purpose of this study is to evaluate the performance of recently developed tumor marker clinical kits in China, with the aim of encouraging local medical technology innovation and thus narrowing the research and development gap with foreign kits. Methods: The newly established reagent kits were analyzed on the TESMI F3999-Luminex200 flow lattice instrument to verify precision, sensitivity (blank limit), linearity, anti-interference ability, carry-over contamination rate, hook effect, and reference interval verification. Additionally, the newly established reagent kits were compared to other commercially available detection kits (reference reagent kits) to analyze the correlation between the two types of kits. Results: The intra-assay and inter-assay precision had coefficients of variations (CVs) less than 3.50% and 6.91%, respectively. The tumor marker blank limits were lower than the manufacturer's statement. The newly established reagent kits demonstrated excellent linearity (r > 0.99). Rheumatoid factor, triglycerides, bilirubin, and hemoglobin did not have significant interference with the determination of tumor markers. The carry-over contamination rates were all much lower than 3%. At extremely high concentrations of AFP (277,335 ng/mL and 1,031,424 ng/mL), the measured tumor marker values were higher than the upper limit of the linear range and no hook effect occurred. The reference interval was suitable for use in clinical laboratory settings. Correlation analysis indicated a satisfactory relevance and consistency between the newly developed reagent kits and reference reagent kits, with correlation coefficients of r > 0.967 among 654 patients and healthy individuals. Conclusions: The newly developed reagent kits for tumor markers performed well in all evaluated parameters, having the potential for clinical promotion and application. [ABSTRACT FROM AUTHOR]

BackgroundThe EXXELERATE study revealed poorer clinical outcomes in patients treated with adalimumab (ADL) and baseline rheumatoid factor (RF) above 203 IU/mL. However, responses were similar in patients treated with certolizumab pegol (CZP) regardless of RF levels.ObjectivesThis study investigated the impact of RF levels >203 IU/mL on TNF inhibitors (TNFi) serum levels and the association with secondary nonresponse in RA patients treated with TNFi.MethodsWe performed an observational ambispective study with RA patients treated with infliximab (IFX), ADL, or CZP. Patients were stratified according to baseline RF levels: ≤ or >203 IU/mL. After 6 months, serum drug levels and antidrug antibodies were measured, and reasons for discontinuation were collected.ResultsWe included 170 RA patients: 90 (53%) received IFX, 48 (28%) ADL, and 32 (19%) CZP. While CZP serum levels did not differ between RF groups at 6 months (p = 0.6), RF levels >203 IU/mL were linked to lower serum drug levels in patients treated with IFX (p = 0.09) or ADL (p = 0.02). Secondary nonresponse was 3.6 times higher in patients with high versus low RF levels in patients under IFX or ADL. However, the reasons for withdrawal were not affected by RF levels in patients treated with CZP.ConclusionBaseline RF above 203 IU/mL is associated with lower serum drug levels and an increased risk of discontinuation due to secondary nonresponse in patients treated with IFX or ADL. In contrast, drug levels and clinical outcomes are not significantly impacted by baseline RF levels in patients under CZP.