Seropositive Rheumatoid Arthritis Research Articles

Identification of autoantibodies against PsoP27 in synovial fluid derived from psoriatic arthritis and rheumatoid arthritis patients

PsoP27 is an antigen expressed in psoriatic lesions. It plays an inflammatory role in psoriasis. This study objective was to characterize antibodies (Abs) against PsoP27 in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Levels of Abs against native and citrullinated PsoP27 in PsA and RA patients’ synovial fluid (SF) and sera were determined by ELISA. SF of osteoarthritis (OA) patients and sera of healthy donors were used as controls. Levels of Abs against PsoP27 were correlated with disease activity scores. Abs against native and citrullinated PsoP27 levels in SF of PsA (n = 48; 0.38 ± 0.03 and 0.44 ± 0.04, respectively) and RA (n = 22; 0.57 ± 0.1 and 0.62 ± 0.09, respectively) were significantly higher than in OA patients (n = 23; 0.14 ± 0.01 and 0.15 ± 0.01, respectively) (p < .0001). For both Abs, there were no significant differences between their level in PsA and RA patients. There was no difference in the level of Abs against citrullinated PsoP27 in SF of seronegative versus seropositive RA patients. Levels of Abs against both native and citrullinated PsoP27 in the SF and level of systemic C-reactive protein in PsA correlated positively, while in RA there were no significant correlations with disease activity scores. No differences in level of Abs against PsoP27 were found in the sera of all three study groups. Abs against native and citrullinated PsoP27 are present in PsA and RA SF but not in those of OA patients, suggesting a potential role of those Abs in inflammatory joint diseases.

Serum and urine lipidomic profiles identify biomarkers diagnostic for seropositive and seronegative rheumatoid arthritis.

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. 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. 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. 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.

Association between Mycobacterium tuberculosis infection and the risk of inflammatory arthritides.

Tuberculosis is a highly contagious disease that has a significant impact on global health. Emerging evidence suggests that tuberculosis can lead to an altered immune response. We investigated the association between tuberculosis and the onset of inflammatory arthritides (IA). Patients with incident tuberculosis in the South Korean National Claims database from 2010 to 2021 were included, and those who had undergone appendectomy during 2010-2011 served as controls. The onset of IA (including seropositive rheumatoid arthritis [SPRA], ankylosing spondylitis [AS], and psoriatic arthritis [PsA]) after tuberculosis was compared between patients with tuberculosis and the control group. Sensitivity analysis was performed using stabilised inverse probability of treatment weighting (sIPTW). A total of 408,685 patients with tuberculosis and 159,675 controls were included. During the mean follow-up of 7.5 years, a total of 1,957 (0.3%) were diagnosed with IA (SPRA, 1,397; AS, 481; and PsA, 79). Multivariable Cox hazard analysis indicated that the overall risk of IA was elevated in the tuberculosis group (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.51-1.93) compared with controls. This increased incidence in patients with tuberculosis was identical among IA subgroups even after adjustment (SPRA [HR, 1.72; 95% CI, 1.49-2.00], AS [HR, 1.64; 95% CI, 1.30-2.06], and PsA [HR, 2.59; 95% CI, 1.32-5.07]) and was replicated in the sIPTW. The increased overall risk of developing IA after tuberculosis corroborates the hypothesis that tuberculosis can trigger dysregulated immunity. This necessitates an increased awareness of autoimmunity in this patient group.

Clinical Phenotypes, Serological Biomarkers, and Synovial Features Defining Seropositive and Seronegative Rheumatoid Arthritis: A Literature Review.

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.

E034 Drug-induced accelerated nodulosis in a patient with rheumatoid arthritis

Abstract Background/Aims Drug-induced accelerated nodulosis (DIAN) is characterized by the occurrence or progression of multiple subcutaneous nodules in a patient treated for rheumatoid arthritis (RA). It was first and most commonly reported with methotrexate in RA patients. Methods A 37-year-old normotensive, non-diabetic, seropositive rheumatoid arthritis female presented with complaints of nodules over the bilateral hands and feet from the last three months. The treatment history included methotrexate therapy (10 mg/week) for one year. Methotrexate-induced rheumatoid accelerated nodulosis (MIAN) was suspected. Methotrexate was stopped and hydroxychloroquine was added considering the low disease activity. The nodules decreased in number as well as size. On follow-up, she presented with increased multiple joint pain and swelling with ESR 60 mm/hour, CRP 13.6 mg/L, and leflunomide was added. After six months of leflunomide use, she again developed multiple bilateral nodules on the extensor and palmar surface of fingers and feet, ranging from 0.5 to 1 cm. The CRP was 9.2 mg/L, ESR 80 mm/hour, complete blood count showed mild anaemia with normal renal and liver function tests. The nodule biopsy showed palisading granuloma consisting of lymphocytes and histiocytes in mid and deep reticular dermis with large foci of fibrin deposition and collagen degeneration s/o rheumatoid nodule. Leflunomide was stopped. Results The leflunomide was switched to sulfasalazine along with colchicine, and hydroxychloroquine was continued. The patient is doing well on follow-up in terms of disease activity and nodule size. Palmeiro. A.G., et al. 2022 reviewed 39 studies from 1st Jan 1988 to 1st Jan 2022 and found 109 cases of accelerated nodulosis. 99 patients had RA, methotrexate was the culprit drug in 89, followed by etanercept in 7 and leflunomide was in just 3 patients. Although there are no exact treatment guidelines, tumour necrosis factor inhibitors were avoided due to increased nodulosis risk. Recently, Valor-Méndez. L., et al 2020 reported improved nodulosis with Janus Kinase inhibitors like baricitinib, which seems to be a future option. Histologically, rheumatoid nodules and accelerated nodulosis are indistinguishable. The exact pathogenesis is unknown but, polymorphic variants of methionine synthase reductase or haplotype HLA-DRB1*0401, and adenosine A1 receptor promotion in multinucleated giant cells are associated. Conclusion Drug-induced accelerated nodulosis (DIAN) and MIAN are not that rare but diagnosis is challenging. It causes significant morbidity and affects the quality of life because of the predominant involvement of hands and feet. It should be suspected especially when disease activity is low or rapidly progressive nodules with a change in immunotherapy. Partial to total improvement can be achieved by identifying and stopping the culprit drug. We need specific guidelines, more treatment options, and a specific national registry to report such adverse effects with biologics and non-biologic disease-modifying antirheumatic drugs. Disclosure H. Singh: None. R. Kaur: None. G. Mohan: None.

E032 Low dose methotextrate induced leukoencephalopathy: a case report

Abstract Background/Aims Methotextrate is a widely used disease modifying anti-rheumatic drug (DMARD) used to treat connective tissue disorder and inflammatory arthritis. Methotextrate induced neurological toxicity includes vomiting, headaches, blurred vision, mood alteration, somolescence, brain fog, hyperosmia, leukoencephalopathy and pseudo-stroke like syndrome. Here we report a case of methotextrate induced headache with leptomeningeal enhancement, which reversed after stopping the methotextrate. Methods A 66 year old male with known diagnosis of sero-positive rheumatoid arthritis with past medical history of Hodgkins lymphoma in remission. He started on dual DMARD combination of 15 mg methotextrate subcutaneously once a week and 200 mg hydroxychlroquin twice daily. Thereafter he reported history of headaches, which needed hospital admission. He underwent a CT-head scan on admission which did not show any acute concerns. The case was then discussed with the haematology team and later he underwent a PET scan of the whole body which was reviewed in Lymphoma MDT which showed non-specific uptake in hilar nodes, which does not significantly increase the suspicion of lymphoma relapse. On discharge he had MRI head contrast and MRV cerebral veins, which showed a few areas of irregular nodular curvilinear foci of predominantly meningeal enhancement noted in occipital lobes and adjacent T2 /flair hypertense signal noted in relation to these. These changes were discussed in neurology MDT, given the history of lymphomas a possibility, though rare in the absence of systemic relapse. The differential included low dose (oral) methotextrate related neurotoxicity. Patient was advised to stop methotextrate, they repeated MRI scan 3 weeks later which showed disappearance of the curvilinear lesions with leptomeningeal enhancement and patient reported headaches improved. Results List of investigations 1. CSF- profile, no protein, no growth 2. CSF PCR panel for Adeno/Paracheo/Entero/Varicella Zoster/HSV type 1&amp;2-negative 3. Histology report of CSF- No evidence of lymphoma 4. Neuronal Ab: Purkinje cell/ Hu Ab/Ri Ab amd Anti-amphiphysin Ab-negative 5. Myeloma screen- no paraprotein detected 6. Virus panel- EBV- IgM-, HIV /Hep B and C, Cytomegalovirus IgM-not detected. Conclusion Methotextrate is a potent anti-metabolite preventing the formation of tetrahydrofolate, and used as immunosuppressant and anti-neoplastic medication. Though the exact mechanism of the neurotoxicity is not known, the common hypothesis include; interference with myelin synthesis or maintenance and/or interference with neurotransmitter synthesis. The case reported here reiterates the importance of recognizing the neurological side effects in patients on methotextrate even on low dose of methotextrate. It also emphasizes the fact that the neurological changes are reversible on stopping methotextrate. Headaches can still be a side effect and might mimic stroke like episode in patients treated with low dose of subcutaneous methotextrate and hence stopping the medication should be considered in such cases. Disclosure P. Doddamani: None. A. Kinder: None.

P049 Genetic liability to rheumatoid arthritis and the risk of cardiometabolic diseases

Abstract Background/Aims Patients with rheumatoid arthritis (RA) are at an increased risk of comorbidities. Previous studies have reported a positive association between RA and cardiometabolic disease risk. However, few causal inference studies have addressed the different serological subtypes of RA and their association with cardiometabolic disease risk. This Mendelian randomisation (MR) study was conducted to offer insight into the causal pathway underlying this association. Methods A two-sample MR analysis was conducted using genetic variants as instrumental variables (IVs) to estimate the causal effect of genetic liability to RA and its serological subsets (seropositive and seronegative) on cardiometabolic disease risk including hypertension, coronary artery disease (CAD), atrial fibrillation, heart failure, stroke, and type 2 diabetes mellitus (T2DM). IVs were obtained from two genome-wide association studies (GWASs) for RA (53,663 cases and 1,064,978 controls [n =177 IVs]). Summary statistics were stratified for serological status including seropositive RA (RA+; 35,240 cases, [n = 195 IVs]), and seronegative RA (RA−; 8,515 cases, [n = 12 IVs]). Both subsets were compared to 990,155 controls. Summary statistics for cardiometabolic diseases were extracted from GWASs of European ancestries. Results The inverse-variance weighted (IVW) model showed a positive association between genetic liability to RA and the risk of CAD, heart failure, and T2DM; CAD, (Odds ratio [OR] = 1.04; 95% confidence interval [CI] 1.01-1.06; P-value [P] = 2.7210-3, heart failure, OR = 1.03; 95% CI 1.01-1.06; P = 0.018, and T2DM, OR = 1.08; 95% CI 1.05-1.11; P = 4.6310-8.). A similar association direction was observed between genetic liability to RA+ and the risk of CAD and T2DM; CAD, (OR = 1.02; 95% CI 1.01-1.04; P = 0.009, T2DM, OR = 1.05; 95% CI 1.03-1.07; P = 3.9110-7). Genetic liability to RA− was positively associated with T2DM risk; (OR = 1.09; 95% CI 1.02-1.16; P = 0.011). Conclusion In this MR study, a positive association of genetic liability to RA was demonstrated with CAD, heart failure and T2DM risk. Genetic liability to RA+ was associated with an increased risk of CAD and T2DM risk while genetic liability to RA− was positively associated with T2DM risk. Future research should investigate genetic architecture of RA including its serological subsets with cardiometabolic diseases to delineate the genes associated with these comorbidities. Disclosure S. Alduhayhi: None. M. Soomro: None. S. Zhao: None. A. Barton: None. A. Morris: None. J. Bowes: None.

Rheumatoid arthritis and idiopathic pulmonary fibrosis: a bidirectional Mendelian randomisation study.

A usual interstitial pneumonia (UIP) pattern of lung injury is a key feature of idiopathic pulmonary fibrosis (IPF) and is also observed in up to 40% of individuals with rheumatoid arthritis (RA)-associated interstitial lung disease (RA-ILD). The RA-UIP phenotype could result from either a causal relationship of RA on UIP or vice versa, or from a simple co-occurrence of RA and IPF due to shared demographic, genetic or environmental risk factors. We used two-sample bidirectional Mendelian randomisation (MR) to test the hypothesis of a causal effect of RA on UIP and of UIP on RA, using variants from genome-wide association studies (GWAS) of RA (separately for seropositive (18 019 cases and 991 604 controls) and seronegative (8515 cases and 1 015 471 controls) RA) and of IPF (4125 cases and 20 464 controls) as genetic instruments. Sensitivity analyses were conducted to assess the robustness of the results to violations of the MR assumptions. IPF showed a significant causal effect on seropositive RA, with developing IPF increasing the risk of seropositive RA (OR=1.06, 95% CI: 1.04 to 1.08, p<0.001) which was robust under all models. For the MR in the other direction, seropositive RA showed a significant protective effect on IPF (OR=0.93; 95% CI: 0.87 to 0.99; p=0.032), but the effect was not significant when sensitivity analyses were applied. This was likely because of bias due to exclusion of patients with RA from among the cases in the IPF GWAS, or possibly because our genetic instruments did not fully capture the effect of the complex human leucocyte antigen region, the strongest RA genetic risk factor. Our findings support the hypothesis that RA-UIP may be due to a cause-effect relationship between UIP and RA, rather than due to a coincidental occurrence of IPF in patients with RA. The significant causal effect of IPF on seropositive RA suggests that pathomechanisms involved in the development of UIP may promote RA, and this may help inform future guidelines on screening for ILD in patients with RA.

Ultrasonographic Evaluation of the Ankle Joint in Relation to Rheumatoid Factor Status and Disease Activity in Patients with Rheumatoid Arthritis

Abstract Background: Rheumatoid arthritis (RA) is a form of inflammatory disease whose clinical pattern is largely dependent on the presence of both anti-citrullinated protein antibodies and rheumatoid factor (RF). Although this is still debatable, seronegative RA seems to be a somewhat less serious condition. The present study aimed to evaluate ankle joint ultrasound in relation to RF status and disease activity in RA patients. Methods: A cross-sectional study involving RA patients from a single center was conducted. Laboratory test evaluations and clinical activity assessments were carried out. The ankle joint was examined using musculoskeletal ultrasound (US). Results: The study included 100 patients with established RA in total. Eighty-two patients tested positive for RF with a mean age of 42.3, whereas only 18 tested negative with a mean age of 39.6. Patients who tested positive for RF had a longer duration of illness (9.39 ± 5.39 vs. 4.56 ± 3.24). There were no differences in clinical activity scores between the seropositive and seronegative groups. The pathological US findings of any ankle joint showed no differences between the seropositive and seronegative groups. Patients with US findings of tibialis posterior tenosynovitis in the left ankle and synovitis and erosion in the right ankle, particularly in the tibiotalar and talonavicular joints, had significantly high Disease Activity Score 28-Erythrocyte sedimentation rate-scores. The increased disease activity was accompanied by significant erosions on both ankles. Conclusion: In terms of disease activity, there is no clinically significant difference between seropositive and seronegative RA patients. Sonographic ankle joint abnormalities do not appear to be associated with the patients’ RF status. High RA disease activity, on the other hand, is associated with synovitis and erosions, particularly in the talonavicular and tibiotalar joints, as well as tibialis posterior tenosynovitis.

Accelerated biological aging as a potential risk factor for rheumatoid arthritis.

Previous studies have suggested a potential correlation between rheumatoid arthritis (RA) and biological aging, but the intricate connections and mechanisms remain elusive. In our study, we focused on two specific measures of biological age (PhenoAge and BioAge), which are derived from clinical biomarkers. The residuals of these measures, when compared to chronological age, are defined as biological age accelerations (BAAs). Utilizing the extensive UK Biobank dataset along with various genetic datasets, we conducted a thorough assessment of the relationship between BAAs and RA at both the individual and aggregate levels. Our observational studies revealed positive correlations between the two BAAs and the risk of developing both RA and seropositive RA. Furthermore, the genetic risk score (GRS) for PhenoAgeAccel was associated with an increased risk of RA and seropositive RA. Linkage disequilibrium score regression (LDSC) analysis further supported these findings, revealing a positive genetic correlation between PhenoAgeAccel and RA. PLACO analysis identified 38 lead pleiotropic single nucleotide polymorphisms linked to 301 genes, providing valuable insights into the potential mechanisms connecting PhenoAgeAccel and RA. In summary, our study has successfully revealed a positive correlation between accelerated biological aging, as measured by BAAs, and the susceptibility to RA.

Investigating the Bidirectional Association of Rheumatoid Arthritis and Thyroid Function: A Methodologic Assessment of Mendelian Randomization.

Rheumatoid arthritis (RA) and thyroid dysfunction are frequently observed in the same patient. However, whether they co-occur or exhibit a causal relationship remains uncertain. We aimed to systematically investigate the causal relationship between RA and thyroid function using a large sample and advanced methods. Bidirectional two-sample Mendelian randomization (MR) analysis was performed based on RA and six thyroid function trait data sets from the European population. The robustness of the results was demonstrated using multiple MR methods and a series of sensitivity analyses. Multivariable MR using Bayesian model averaging (MR-BMA) was performed to adjust for possible competing risk factors. A sensitivity data set, which included data from patients with seropositive RA and controls, was used to repeat the analyses. Furthermore, enrichment analysis was employed to discover the underlying mechanism between RA and thyroid functions. A significantly positive causal effect was identified for RA on autoimmune thyroid disease (AITD) as well as for AITD on RA (P < 0.001). Further sensitivity analyses showed consistent causal estimates from a variety of MR methods. After removing the outliers, MR-BMA results showed that RA and AITD were independent risk factors in their bidirectional causality, even in the presence of other competing risk factors (adjusted P < 0.05). Enrichment analysis showed immune cell activation and immune response play crucial roles in them. Our results illustrate the significant bidirectional causal effect of RA and AITD, which holds even in multiple competing risk factors. Clinical screening for thyroid dysfunction in patients with RA deserves further attention, and vice versa.

Low-frequency and rare genetic variants associated with rheumatoid arthritis risk.

Rheumatoid arthritis (RA) has an estimated heritability of nearly 50%, which is particularly high in seropositive RA. HLA alleles account for a large proportion of this heritability, in addition to many common single-nucleotide polymorphisms with smaller individual effects. Low-frequency and rare variants, such as those captured by next-generation sequencing, can also have a large role in heritability in some individuals. Rare variant discovery has informed the development of drugs such as inhibitors of PCSK9 and Janus kinases. Some 34 low-frequency and rare variants are currently associated with RA risk. One variant (19:10352442G>C in TYK2) was identified in five separate studies, and might therefore represent a promising therapeutic target. Following a set of best practices in future studies, including studying diverse populations, using large sample sizes, validating RA and serostatus, replicating findings, adjusting for other variants and performing functional assessment, could help to ensure the relevance of identified variants. Exciting opportunities are now on the horizon for genetics in RA, including larger datasets and consortia, whole-genome sequencing and direct applications of findings in the management, and especially treatment, of RA.

Association of HLA-DRB1 locus with treatment response to abatacept or TNF inhibitors in patients with seropositive rheumatoid arthritis

The strongest genetic risk factor for rheumatoid arthritis (RA) has been known as HLA-DRB1 based on amino acid positions 11, 71, and 74. This study analyzed the association between specific HLA-DRB1 locus and treatment response to abatacept or TNF inhibitors (TNFi) in patients with seropositive RA. A total of 374 Korean RA patients were treated with abatacept (n = 110) or TNFi (n = 264). Associations between HLA-DRB1 and treatment response after 6 months were analyzed using multivariable logistic regression. Seropositive RA patients with HLA-DRB1 shared epitope (SE) had a favorable response to abatacept (OR = 3.67, P = 0.067) and an inversely associated response to TNFi (OR 0.57, P = 0.058) based on EULAR response criteria, but the difference was not statistically significant in comparison to those without SE. In analyses using amino acid positions of HLA-DRB1, a significant association was found between valine at amino acid position 11 of SE and good response to abatacept (OR = 6.46, P = 5.4 × 10–3). The VRA haplotype also showed a good response to abatacept (OR = 4.56, P = 0.013), but not to TNFi. Our results suggest that treatment response to abatacept or TNFi may differ depending on HLA-DRB1 locus in seropositive RA, providing valuable insights for selecting optimal therapy.

Patterns of reproductive health in inflammatory rheumatic diseases and other immune-mediated diseases: a nationwide registry study.

Rheumatic diseases may impair reproductive success and pregnancy outcomes, but systematic evaluations across diseases are lacking. We conducted a nationwide cohort study to examine the impact of rheumatic diseases on reproductive health measures, comparing the impacts with those of other immune-mediated diseases (IMDs). Out of all of the 5 339 804 Finnish citizens, individuals born 1964-1984 and diagnosed with any of the 19 IMDs before age 30 (women) or 35 (men) were matched with 20 controls by birth year, sex, and education. We used data from nationwide health registers to study the impact of IMDs on reproductive health measures, such as reproductive success and, for women, ever having experienced adverse maternal and perinatal outcomes. Several of the rheumatic diseases, particularly SLE, JIA, and seropositive RA, were associated with higher rates of childlessness and fewer children. The risks for pre-eclampsia, newborns being small for gestational age, preterm delivery, non-elective Caesarean sections, and need of neonatal intensive care were increased in many IMDs. Particularly, SLE, SS, type 1 diabetes, and Addison's disease showed >2-fold risks for some of these outcomes. In most rheumatic diseases, moderate (1.1-1.5-fold) risk increases were observed for diverse adverse pregnancy outcomes, with similar effects in IBD, celiac disease, asthma, ITP, and psoriasis. Rheumatic diseases have a broad impact on reproductive health, with effects comparable with that of several other IMDs. Of the rheumatic diseases, SLE and SS conferred the largest risk increases on perinatal adverse event outcomes.

Background and objectives: Acute coronary syndrome is the leading cause of death all over the world, there are many different risk factors as important etiology for this acute condition, this syndrome has been studied in different countries with a variety of results. The aim was to define different risk factors for the patients admitted to Erbil cardiac center and to

Background and objectives: The most prevalent and chronic form of systemic autoimmune disease, rheumatoid arthritis is characterized by persistent inflammation, deteriorating joint function with time, increasing comorbidity, and increased mortality. The aim of this study was to know the frequency of joints involved, to know the prevalence of seropositive Rheumatoid arthritis, and evaluation of demographic features of the patients with Rheumatoid arthritis. Methods: A cross-sectional, descriptive study was undertaken on 110 patients at Rizgary teaching hospital in Erbil city. From January 2022 and January 2023. We evaluated and diagnosed the patients. Serological investigations including Anti-cyclic citrullinated peptide and rheumatoid factor were done for all of the patients. Results: One hundred ten patients 80% were female and 20 % were male. The mean age (SD) was 51.39 (12.6) years, majority of the patients were obese (45.5%). Only 14.5% of the sample were smokers, and rate of illiteracy was 60%. The most common joints involved were metacarpo-pharyngeal joint 73.6% followed by wrist joint 63.6%. Most common comorbid disease was hypertension 29.1% followed by diabetes mellitus, and thyroid disease (15.5%, 10%) respectively. Prevalence of seropositive rheumatoid arthritis was 80.9%. Majority of the patients used methotrexate, while the most common biologic used by the patients was etanercept 12.7%. Conclusions: Our rheumatoid arthritis patients' demographics, joint involvement, and serological characteristics matched those of some regional and international studies, however we discovered a higher proportion of women and a higher percentage of illiteracy.

Rheumatoid Arthritis and Risk of Depression in South Korea

Depression is among the most common comorbidities in rheumatoid arthritis (RA). There is a lack of data regarding the association of RA seropositivity and biologic agents with depression risk among individuals with RA. To investigate the risk of depression following RA diagnosis among patients in South Korea. This retrospective cohort study included 38 487 patients with RA and a comparison group of 192 435 individuals matched 1:5 for age, sex, and index date. Data were from the Korean National Health Insurance Service database. Participants were enrolled from 2010 to 2017 and were followed up until 2019. Participants who had previously been diagnosed with depression or were diagnosed with depression within 1 year after the index date were excluded. Statistical analysis was performed in May 2023. Seropositive RA (SPRA) was defined with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes M05 and enrollment in the Korean Rare and Intractable Diseases program. Seronegative RA (SNRA) was defined with ICD-10 codes M06 (excluding M06.1 and M06.4) and a prescription of any disease-modifying antirheumatic drugs (DMARDs) for 270 days or more. Newly diagnosed depression (ICD-10 codes F32 or F33). The mean (SD) age of the total study population was 54.6 (12.1) years, and 163 926 individuals (71.0%) were female. During a median (IQR) follow-up of 4.1 (2.4-6.2) years, 27 063 participants (20 641 controls and 6422 with RA) developed depression. Participants with RA had a 1.66-fold higher risk of depression compared with controls (adjusted hazard ratio [aHR], 1.66 [95% CI, 1.61-1.71]). The SPRA group (aHR, 1.64 [95% CI, 1.58-1.69]) and the SNRA group (aHR, 1.73 [95% CI, 1.65-1.81]) were associated with an increased risk of depression compared with controls. Patients with RA who used biologic or targeted synthetic DMARDs (aHR, 1.33 [95% CI, 1.20-1.47]) had a lower risk of depression compared with patients with RA who did not use these medications (aHR, 1.69 [95% CI, 1.64-1.74]). This nationwide cohort study found that both SPRA and SNRA were associated with a significantly higher risk of depression. These results suggest the importance of early screening and intervention for mental health in patients with RA.

The gut-joint axis: Genetic evidence for a causal association between gut microbiota and seropositive rheumatoid arthritis and seronegative rheumatoid arthritis.

This study aimed to assess the causal relationship between GM and RA (seropositive RA and seronegative RA). A two-sample Mendelian randomization (MR) analysis was performed to assess the causality of GM on seropositive RA and seronegative RA. GM's genome-wide association study (GWAS) was used as the exposure, whereas the GWAS datasets of seropositive RA and seronegative RA were the outcomes. The primary analysis approach was used as inverse-variance weighted (IVW), followed by 3 additional MR methods (MR-Egger, weighted median, and weighted mode). Cochran's Q test was used to identify heterogeneity. The MR-Egger intercept test and leave-one-out analyses were used to assess horizontal pleiotropy. All statistical analyses were performed in R software. We discovered that Alloprevotella (IVW OR 0.84, 95% CI 0.71-0.99, P = .04) and Christensenellaceae R 7 group (IVW OR 0.71, 95% CI 0.52-0.99, P = .04) were negatively correlated with seropositive RA, Ruminococcaceae UCG002 (IVW OR 1.30, 95% CI 1.10-1.54, P = .002) was positively associated with seropositive RA. Actinomyces (IVW OR 0.73, 95% CI 0.54-0.99, P = .04), Christensenellaceae R 7 group (IVW OR 0.62, 95% CI 0.39-0.97, P = .04), Terrisporobacter (IVW OR 0.64, 95% CI 0.44-0.93, P = .02), Lactobacillales (IVW OR 0.65, 95% CI 0.47-0.90, P = .01) were negatively correlated with seronegative RA. The present MR analysis showed a protective effect of Alloprevotella and Christensenellaceae R 7 group and a potentially anti-protective effect of Ruminococcaceae UCG002 on seropositive RA; and a protective effect of Actinomyces, Christensenellaceae R 7 group, Terrisporobacter, and Lactobacillales on seronegative RA. Further experimental studies and randomized controlled trials are needed to validate these findings.

Investigation of periodontitis, halitosis, xerostomia, and serological characteristics of patients with osteoarthritis and rheumatoid arthritis and identification of new biomarkers.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are two different types of arthritis. Within RA, the subsets between seronegative RA (snRA) and seropositive RA (spRA) represent distinct disease entities; however, identifying clear distinguishing markers between them remains a challenge. This study investigated and compared the oral health conditions in patients with RA and OA to clarify the differences from healthy controls. In addition, we investigated the serological characteristics of the patients, the factors that distinguished patients with RA from those with OA, and the main factors that differentiated between snRA and spRA patients. A total of 161 participants (mean age: 52.52 ± 14.57years, 32 males and 129 females) were enrolled in this study and categorized as: normal (n = 33), OA (n = 31), and RA (n = 97). Patients with RA were divided into the following two subtypes: snRA (n = 18) and spRA (n = 79). Demographics, oral health, and serological characteristics of these patients were compared. The prevalence of periodontal diseases was significantly higher in patients with OA (100%) and RA (92.8%) than in healthy controls (0.0%). However, the presence of periodontal diseases was not utilized as a distinguishing factor between OA and RA. Xerostomia occurred more frequently in patients with RA (84.5%) than in patients with OA (3.2%) and healthy controls (0.0%) (all p < 0.001). ROC analysis revealed that periodontal disease was a very strong predictor in the diagnosis of OA compared to healthy controls, with an AUC value of 1.00 (p < 0.001). Additionally, halitosis (AUC = 0.746, 95% CI 0.621-0.871, p < 0.001) and female sex (AUC = 0.663, 95% CI 0.529-0.797, p < 0.05) were also significant predictors of OA. The strongest predictors of RA diagnosis compared to healthy controls were periodontal diseases (AUC = 0.964), followed by xerostomia (AUC = 0.923), age (AUC = 0.923), female sex (AUC = 0.660), and halitosis (AUC = 0.615) (all p < 0.05). Significant serological predictors of RA were anti-CCP Ab (AUC = 0.808), and RF (AUC = 0.746) (all p < 0.05). In multiple logistic regression analysis, xerostomia (odds ratio, OR: 8124.88, 95% CI 10.37-6368261.97, p-value = 0.008) and Anti-CCP Ab (OR: 671.33, 95% CI 2.18-207,074.02, p = 0.026) were significant predictors for RA compared to OA. When diagnosing spRA compared to snRA, anti-CCP Ab (AUC = 1.000, p < 0.001) and RF (AUC = 0.910, 95%CI 0.854-0.967, p < 0.001) had outstanding predictive performances. Therefore, clinicians and researchers should thoroughly evaluate the oral status of both OA and RA patients, alongside serological factors, and consider these elements as potential predictors.

Isolated dextrocardia and rheumatoid arthritis with mitral stenosis with pulmonary hypertension with atrial fibrillation: A rare association

This case presents a rare occurrence of rheumatoid arthritis (RA) in a 50-year-old woman with concurrent mitral valvular disease and dextrocardia. Diagnosed with seropositive RA 5 years earlier, the patient exhibited fever, cough, and progressive dyspnea. Clinical examination revealed irregular tachycardia, elevated jugular venous pressure, and signs of heart failure. Laboratory results confirmed seropositive RA, anemia, and elevated inflammatory markers. Electrocardiogram and echocardiogram indicated dextrocardia, atrial fibrillation, and moderate mitral stenosis. This case highlights the unusual association of RA with valvular heart disease and the added complexity of dextrocardia. Recognizing diverse cardiac manifestations in RA is crucial, contributing to the growing evidence linking autoimmune disorders to cardiovascular complications. Further research is essential to understand the intricate relationship between RA and unique cardiac abnormalities.

Does Rheumatoid Arthritis Increase the Risk of COPD?: A Nationwide Retrospective Cohort Study

BackgroundMost reports of pulmonary manifestations in rheumatoid arthritis (RA) have been related to interstitial lung diseases. RA and chronic obstructive pulmonary disease (COPD) are both chronic inflammatory systemic diseases. Research QuestionDoes RA increase the risk of developing COPD? Is there a difference between seropositive and seronegative RA in the risk of COPD? Study Design and MethodsUsing the Korean National Health Insurance Database, we screened individuals diagnosed with RA between 2010 and 2017. We identified 46,030 patients with RA (32,608 seropositive RA and 13,422 seronegative RA) and 276,180 matched control individuals, and monitored them until December 2019. We used multivariate Cox proportional hazard models to estimate the adjusted hazard ratio (aHR) of risk factors for the development of COPD. ResultsThe incidence of COPD among patients with RA was 5.04/1,000 person-year and 2.23/1,000 person-year in the control group. Patients with RA showed a higher risk of developing COPD (aHR 2.11, 95% confidence interval [CI] 1.96–2.28) compared with the control group. While both seropositive RA and seronegative RA were associated with an increased risk of COPD, patients with seropositive RA had a higher risk for the development of COPD (aHR 1.26, 95% CI 1.09–1.46) compared with patients with seronegative RA. In the subgroup analyses, smoking history did not demonstrate significant interactions between RA and COPD development. InterpretationRA is associated with an increased risk of COPD development, augmented by seropositivity. Clinicians should monitor respiratory symptoms and pulmonary function carefully in patients with RA.