Search Results (24)

Background and Clinical Significance: Antisynthetase syndrome (ASyS) is a rare autoimmune entity defined by the presence of anti-aminoacyl-t ribonucleic acid (RNA) synthetase autoantibodies and classically associated with a triad of interstitial lung disease (ILD), inflammatory myopathy, and arthritis. Additional clinical features may include Raynaud’s phenomenon and “mechanic’s hands”. Among antisynthetase antibodies, anti-PL-12 is notably associated with predominant or isolated ILD and may occur in the absence of clinically evident myositis, thereby complicating timely diagnosis. Case Presentation: We are presenting a 45-year-old non-smoking female patient with a prior diagnosis of seronegative rheumatoid arthritis (RA) who developed progressive dyspnea, dry cough, and sicca symptoms. High-resolution computed tomography revealed a nonspecific interstitial pneumonia (NSIP) pattern. Despite normal creatine kinase and lactate dehydrogenase levels, serological work-up revealed positive anti-PL-12 and anti-Ro52 antibodies, supporting a diagnosis of antisynthetase syndrome without myositis, fulfilling the diagnostic criteria for ASyS per Connors and Solomon. Treatment with corticosteroids and cyclophosphamide induced clinical and functional respiratory improvement, while azathioprine was initiated for maintenance. Conclusions: This case underscores the clinical heterogeneity of antisynthetase syndrome and highlights the diagnostic challenge posed by anti-PL-12–associated ILD in the absence of myositis. Importantly, it demonstrates that in patients with pre-existing rheumatologic diagnoses, the emergence of atypical pulmonary manifestations warrants repeat serologic evaluation to assess ASyS and other autoimmune conditions. Early diagnosis and immunosuppressive treatment are essential to optimize outcomes. Full article

Background: Rheumatoid arthritis is a relatively common rheumatic disease that can present with inflammatory arthritis and subcutaneous nodules. Multicentric reticulohistiocytosis and fibroblastic rheumatism are rarer entities that also present with these features. Methods: Two cases, one of each of fibroblastic rheumatism and multicentric reticulohistiocytosis, are described highlighting characteristic clinical, radiographic, and histologic findings. A narrative review of the literature on these rarer conditions, compared with rheumatoid arthritis, is provided with a focus on articular and cutaneous findings, available information on disease presentations, and key contrasting features that can aid in diagnosis. Results: Radiographic erosion distribution and joint space narrowing, clinical nodule distribution and characteristics, and nodule histology can differ between these diseases. Conclusions: Multicentric reticulohistiocytosis and fibroblastic rheumatism should be considered in the evaluation of seronegative rheumatoid arthritis, especially in cases that do not respond predictably to standard therapies, and cutaneous nodule biopsy can aid in differentiating these three conditions. Full article

The prevalence of rheumatoid arthritis (RA) subtypes, including seropositive and seronegative, is influenced by lifestyle factors and exhibits high heterogeneity, resulting in reduced drug efficacy. This study aims to identify cytokines mediating the effects of different lifestyles on RA subtypes and to discover new drugs for personalized treatment. Mendelian randomization revealed that three cytokines (MIP1b, SCGFb, and TRAIL) partially mediated the effects of different lifestyles on RA overall or its subtypes. The pretrained model, i.e., DrugBAN, predicted the probability of 723,000 small molecule drugs binding to these three targets. In molecules with high binding rates, we calculated the structural similarity between known drugs for RA and other drugs to screen for new drugs, followed by molecular docking and molecular dynamics simulations for validation. The results indicate that these targets had promising binding affinity with known drugs and other drugs with high similarity. Our findings may guide therapeutic approaches for heterogeneous RA patients with specific lifestyle habits. Full article

Background: Previous studies have demonstrated that the gut microbiota (GM) and rheumatoid arthritis (RA) are significantly associated, but the causal relationship has not been fully elucidated. Methods: We investigated the association between GM and RA using Mendelian randomization (MR) with two independent samples. Our study aimed to determine the causal relationship between gut microbiota and RA, including its seronegative and seropositive subtypes. Using data from a genome-wide association study (GWAS), we identified instrumental variables for 211 gut bacteria types. We then analyzed the FinnGen GWAS dataset, which included 3877 seronegative RA cases and 285,035 controls, along with 4290 seropositive RA cases and 368,362 controls, employing the inverse variance weighted (IVW) method and rigorous tests for pleiotropy and heterogeneity to ensure reliability. Results: The IVW results revealed that Prevotella 9, Sutterella, and Christensenellaceae R.7 exhibited an adverse correlation with seronegative RA (p < 0.05). Additionally, Lachnospira, Slackia, Roseburia, Barnesiella, and Prevotella 7 were associated with a reduced occurrence of seropositive RA (p < 0.05). Conversely, Ruminococcaceae UCG002 and Ruminococcus gauvreauii were linked to an increased susceptibility to seropositive RA (p < 0.05). Notably, no significant heterogeneity (p > 0.05) or pleiotropy (p > 0.05) was detected in the analysis of the significant MR estimates. Conclusions: Our study suggested significant associations between several gut bacteria and RA subtypes, indicating a potential microbial influence on RA development. These findings enhance our understanding of the gut-joint axis in RA and highlight promising targets for future microbiota-based therapies. Full article

Background: Rheumatoid arthritis (RA) is a globally prevalent chronic inflammatory disease. Environmental exposures, such as air pollution and smoking, are considered potential risk factors. However, the causal relationships and underlying mechanisms between these factors and RA are not fully understood. Methods: This study utilized large-scale genome-wide association studies (GWASs) from European ethnic backgrounds and employed bidirectional two-sample Mendelian randomization (MR) to investigate the relationships between air pollution, smoking, and RA. Genetic correlations were assessed using linkage disequilibrium score regression (LDSC). Furthermore, mediation analysis was conducted to evaluate the potential mediating roles of iron metabolism and urinary biomarkers in these relationships. Results: The MR analysis revealed that genetically predicted lifetime smoking intensity was associated with an 85% increased risk of RA. Subgroup analysis differentiating between seropositive RA (SPRA) and seronegative RA (SNRA) showed a causal association with SPRA, but not with SNRA. C-reactive protein was identified as a mediator in the relationship between lifetime smoking and both RA and SPRA, mediating 18.23% and 32.45% of the effects, respectively. Genetic correlation analysis further confirmed a positive genetic association between smoking and both RA and SPRA. Conclusions: This study provides significant insights into the genetic and causal connections between air pollution, smoking, and the development of RA, highlighting the mediating role of C-reactive protein. These findings not only offer new perspectives on how smoking might enhance RA risk through inflammatory pathways but also underscore the importance of reducing smoking exposure in public health strategies. Full article

With the aim of improving the uncertainties associated with the correct diagnosis of seronegative rheumatoid arthritis (RA) and identifying those at risk of developing interstitial lung disease (ILD), we have designed new peptide antigens bearing three post-translational modifications (PTMs) (citrulline, homocitrulline and acetyl-lysine) related to RA that could complement existing tests based on anti-citrullinated peptide/protein antibodies (ACPAs). Several chimeric peptides were synthesized and comparatively tested as antigens in ELISAs with two cohorts of sera: 178 RAs and 110 healthy blood donors. The results indicated that although chimeric peptides containing all three PTMs and vimentin and enolase domains do not significantly outperform existing ACPA tests in terms of sensitivity and specificity, they show potential to complement current assays, especially when detecting antibodies in some seronegative patients. Furthermore, the presence of these autoantibodies significantly identified patients with RA and ILD. We can conclude that the identification of specific autoantibody profiles using synthetic antigens containing peptide domains derived from proteins present in the human joint could help in the early detection of the risk of ILD in patients with RA and be useful for adapting follow-up strategies and guiding decisions during treatment. Full article

Sjögren’s syndrome (SS) is an autoimmune disease characterized by heterogeneous clinical presentation and the presence of various autoantibodies. This study aimed to determine the differences in clinical findings according to antibody positivity in patients with primary Sjögren syndrome (pSS) in the Turkish population. A retrospective study was conducted and 402 patients (378 women and 24 men) with pSS were analyzed. The patients were categorized into three subgroups based on serological tests. These were (1) quadruple seropositivity (positive for anti-Sjögren’s syndrome-related antigen A antibodies (anti-SSA; anti-Ro) and anti-Sjögren’s syndrome-related antigen B antibodies (anti-SSB; anti-La), rheumatoid factor (RF), and antinuclear antibody (ANA); (2) double seropositivity (positive for ANA and anti-SSA/Ro antibodies); and (3) quadruple seronegativity (negative for ANA, RF, anti-SSA/Ro and anti-SSB/La antibodies). The number of quadruple-seropositive patients was 72 (18.6%), double-seropositive 174 (43.2%), and quadruple-seronegative was 85 (21.1%). The age at diagnosis of quadruple-seropositive pSS was 42.4 ± 10.8, which was significantly younger than that of patients with double-seropositive and quadruple-seronegative pSS (p = 0.021, p = 0.112). In terms of organ involvement, salivary gland enlargement, arthralgia, arthritis, Raynaud’s phenomenon, lymphadenopathy, cutaneous vasculitis, interstitial lung disease, neurological involvement, autoimmune thyroiditis, renal interstitial disease, anemia, leukopenia, hypergammaglobulinemia, and hypocomplementemia were more common in quadruple-seropositive patients with pSS than in quadruple-seronegative patients (p < 0.0001). The results of this study confirmed the strong impact of immunological markers on the pSS phenotype at the time of diagnosis. Immunological patterns play a central role in the phenotypic expression of the disease, even during the initial diagnostic phase, and can guide physicians in designing personalized treatment plans for patients with pSS. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune disorder which can lead to long-term joint damage and significantly reduced quality of life if not promptly diagnosed and adequately treated. Despite significant advances in treatment, about 40% of patients with RA do not respond to individual pharmacological agents and up to 20% do not respond to any of the available medications. To address this large unmet clinical need, several recent studies have focussed on an in-depth histological and molecular characterisation of the synovial tissue to drive the application of precision medicine to RA. Currently, RA patients are clinically divided into “seropositive” or “seronegative” RA, depending on the presence of routinely checked antibodies. Recent work has suggested that over the last two decades, long-term outcomes have improved significantly in seropositive RA but not in seronegative RA. Here, we present up-to-date differences in epidemiology, clinical features, and serological biomarkers in seronegative versus seropositive RA and discuss how histological and molecular synovial signatures, revealed by recent large synovial biopsy-based clinical trials, may be exploited to refine the classification of RA patients, especially in the seronegative group. Full article

Background and Objective: Rheumatoid arthritis (RA) is an autoimmune disease in which joints are gradually destroyed. Early diagnosis and treatment before joint deformation or destruction is important. The detection of novel RA biomarkers in saliva may facilitate early detection of RA before disease onset. This study aimed to evaluate salivary concentration of α1-antitrypsin (A1AT) in healthy patients and those with RA, and to assess the diagnostic value of salivary A1AT. Materials and Methods: In total, 80 participants were included: 20 healthy participants, and 60 patients with RA. Saliva and serum samples were obtained from all the patients. Levels of A1AT and cytokines, including interleukin-1 beta (IL-1β), IL-6, and IL-10 in saliva and serum, were evaluated using an enzyme-linked immunosorbent assay kit and Luminex assay. Data were analyzed using SPSS for Windows. Results: There was a higher level of A1AT in the saliva of patients with RA (median: 2388.66 ng/mL) than that in healthy controls (1579.06 ng/mL). There was a positive mild-to-moderate accuracy (area under the curve: 0.57–0.85) of A1AT in saliva to diagnose RA. The cut-off level (ng/mL) of A1AT in saliva for detecting RA was 1689.0. Conclusions: The obtained data can promote the application of the measurements of A1AT in saliva to diagnose RA. Full article

Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood, affecting one to four of every 1000 children worldwide. It is characterized by joint inflammation lasting more than six weeks in children under 16 years. The aim of this study was to estimate the frequency of JIA subtypes in the Mexican patient population; compare clinical, immunological and inflammation markers by JIA subtype; and examine the correlation between these variables. Methods: We conducted a cross-sectional study of 50 patients with JIA (2–15 years). We estimated the frequency of each JIA subtype, assessed and compared the immunological characteristics (RF, ANA and anti-CCP) by JIA subtype at the time of diagnosis using Kruskal–Wallis or chi-square tests, and calculated Spearman correlation coefficients between the assessments. Results: Our analysis included 50 patients, 29 (58%) girls and 21 (42%) boys, aged at the time of diagnosis 10.56  ±  3.99 years. The frequencies of JIA subtypes were RF-seropositive polyarthritis (34%), RF-seronegative polyarthritis (28%), systemic arthritis (16%), oligoarthritis (14%) and arthritis-related enthesitis (8%). We found a significant association between sex and JIA subtype (p = 0.014). There was a significant difference in anti-CCP levels by JIA subtype (p < 0.001). We also detected positive correlations between RF and anti-CCP (r = 0.63, p < 0.001) and between age and anti-CCP (r = 0.29, p = 0.041). Conclusions: Our study suggests that the frequency of the polyarticular subtypes of JIA is higher in Mexican children compared to other populations. Our findings highlight the importance of considering the presence of anti-CCP and RF as important criteria when deciding on treatment for JIA patients as elevated levels of these antibodies may indicate early forms of adult rheumatoid arthritis. Full article

Seronegative rheumatoid arthritis (SNRA) is characterized by the absence of both rheumatoid factor (RF) and antibodies against the cyclic citrullinated protein (ACPA) in serum. However, the differences between the two forms of RA are more complex and have not yet been definitively characterized. Several lines of evidences support the idea that there are specific elements of the two forms, including genetic background, epidemiology, pathogenesis, severity of progression over time, and response to therapy. Clinical features that may differentiate SNRA from SPRA are also suggested by data obtained from classical radiology and newer imaging techniques. Although new evidence seems to provide additional help in differentiating the two forms of RA, their distinguishing features remain largely elusive. It should also be emphasized that the distinctive features of RA forms, if not properly recognized, can lead to the underdiagnosis of SNRA, potentially missing the period called the “window of opportunity” that is critical for early diagnosis, timely treatment, and better prognosis. This review aims to summarize the data provided in the scientific literature with the goal of helping clinicians diagnose SNRA as accurately as possible, with emphasis on the most recent findings available. Full article

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. Full article

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

The hand and wrist are among the most common anatomical areas involved in rheumatic diseases, especially seropositive and seronegative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). The purpose of this study was to identify the most differentiating radiographic characteristics of PsA, seropositive RA, and seronegative RA, particularly in the early stages. A retrospective analysis of radiographic hand findings was performed on 180 seropositive RA patients (29 males, 151 females, mean age at the point of acquisition of the analyzed radiograph of 53.4 y/o, SD 12.6), 154 PsA patients (45 males, 109 females, age median of 48.1 y/o, SD 12.4), and 36 seronegative RA patients (4 males, 32 females, age median of 53.1 y/o, SD 17.1) acquired during the period 2005–2020. Posterior–anterior and Nørgaard views were analyzed in all patients. The radiographs were evaluated for three radiographic findings: type of symmetry (asymmetric/bilateral/changes in corresponding joint compartments/‘mirror-image’ symmetry), anatomic location (e.g., wrist, metacarpophalangeal (MCP), proximal interphalangeal (PIP), distal interphalangeal (DIP) joints), and type of lesions (e.g., juxta-articular osteoporosis, bone cysts, erosions, proliferative bone changes). The study showed that symmetric distribution of lesions defined as ‘lesions present in corresponding compartments’ was more suggestive of seropositive or seronegative RA than PsA. Lesions affecting the PIP joints, wrist, or styloid process of the radius; juxta-articular osteoporosis, joint space narrowing, joint subluxations, or dislocations were more common in patients with seropositive RA than in those with PsA, whereas DIP joints’ involvement and proliferative bone changes were more likely to suggest PsA than seropositive RA. Lesions in PIP, MCP, and wrist joints, as well as erosions, advanced bone damage, joint subluxations, dislocations, and joint space narrowing, were more common in seropositive RA patients than in seronegative RA patients. The ulnar styloid was more commonly affected in seronegative RA patients than in PsA patients. The study confirmed that types of bone lesions and their distribution in the hands and wrists can be useful in differentiating seropositive RA from PsA and suggests that seronegative RA varies in radiological presentation from seropositive RA and PsA. Full article

Elderly-onset rheumatoid arthritis (EORA) is prevalent among older patients, and its incidence is increasing due to aging societies. However, differentiating between EORA and polymyalgia rheumatica (PMR) is challenging for clinicians and hinders the initiation of effective treatment for rheumatoid arthritis among older generations, thereby allowing its progression. Therefore, we conducted a qualitative synthesis of narrative reviews via meta-ethnography regarding seronegative EORA diagnosis to clarify the methods to differentiate seronegative EORA from PMR. Three databases (PubMed, EMBASE, and Web of Science) were searched for relevant reviews published between January 2011 and October 2022. The extracted articles were synthesized using meta-ethnography, and 185 studies were selected following the protocol. Seven reviews were analyzed, and four themes and nine concepts were identified. The four themes included difficulty in differentiation, mandatory follow-up, and factors favoring rheumatoid arthritis and those favoring PMR. Factors favoring seronegative EORA and PMR should be considered for effective diagnosis and prompt initiation of disease-modifying anti-rheumatic drugs. Mandatory and long follow-ups of suspected patients are essential for differentiating the two diseases. The attitude of rheumatologists toward tentatively diagnosing seronegative EORA and flexibly modifying their hypotheses based on new or altered symptoms can aid in effective management and avoiding misdiagnosis. Full article