Seropositive Rheumatoid Arthritis Research Articles

Anti-modified protein antibodies can be detected in saliva, but not in intestinal secretions of seropositive rheumatoid arthritis patients - evidence of site-specific mucosal autoantibody secretion in RA.

Anti-citrullinated protein antibodies (ACPA) have been detected in sputum and saliva, indicating that anti-modified protein antibodies (AMPA) can be produced at mucosal sites in rheumatoid arthritis (RA) patients. However, the body's largest mucosal compartment, the gut, has not yet been examined. We therefore investigated the presence of several AMPA (antibodies against citrullinated (ACPA), carbamylated (anti-CarP) and acetylated (AAPA) proteins) at different mucosal sites, including the intestinal tract. Paired fecal/ileal wash, saliva and serum samples of RA patients and healthy volunteers were collected in two independent cohorts. Data involving feces was replicated in a third cohort. In these secretions AMPA were analyzed using in-house ELISA with unmodified peptides as control. In fecal samples total IgA and anti-E. coli IgA were measured. ACPA, anti-CarP and AAPA IgA were measurable in saliva of seropositive RA patients (prevalence 9-40%). No AMPA could be detected in feces. IgA was present since total IgA and anti-E. coli IgA was detectable in feces of ACPA-positive RA patients and healthy donors. Results were confirmed in another cohort using colonoscopically collected ileal wash samples. Our study shows the presence of ACPA, anti-CarP and AAPA IgA in saliva of ACPA-seropositive RA patients. However, no AMPA could be detected in feces/ileal wash samples of these patients, although our assays were able to measure other antigen-specific antibodies. These data suggest that mucosal autoantibody secretion may occur in the oral mucosa of RA patients, while no evidence could be found for this process in the lower gastro-intestinal tract.

Rising? trends in Anxiety and Depression among Individuals with Rheumatoid Arthritis: A Population-Based Study.

To investigate trends in depression and anxiety over three decades among individuals with rheumatoid arthritis (RA). Patients with incident RA (age >18 years, meeting 1987 ACR criteria in 1985-2014) were identified using the Rochester Epidemiology Project. Individuals with RA were matched 1:1 with non-RA comparators on age, sex, and calendar year of RA incidence. Patients were followed until death, migration or 12/31/2020. Depression and anxiety were defined using established ICD9/10 code sets. Cox models were used to compare trends in the occurrence of depression and anxiety diagnoses and cooccurring anxiety and depression by decade and RA status, adjusted for potential confounders. The study included 1,012 individuals with RA and 1,012 matched controls (mean age 55.9 years; 68.38% female). Hazard ratios (HR) demonstrated a temporal increase in anxiety and co-occurring anxiety and depression from 2005-2014 compared to 1985-1994 for individuals both with and without RA. Persons with RA exhibited a rising occurrence of anxiety (HR: 1.27; 95% confidence interval (CI): 0.86-1.88). and concomitant anxiety and depression (HR: 1.49; 95% CI: 0.96-2.33) compared to controls. Trends were most pronounced in seropositive RA patients (HR for anxiety: 4.01; 95% CI: 2.21-7.30). Anxiety and concomitant anxiety and depression diagnoses are elevated in individuals with RA. The increasing occurrence of anxiety and co-occurring anxiety and depression suggests rising awareness and diagnosis of these disorders. Adding to stable but high rates of depression diagnoses, individuals with RA now have evidence of a widening gap in mental health diagnoses that clinicians should address.

Joint hypermobility in rheumatoid arthritis: A case- control study

Objective: To evaluate the presence of joint hypermobility (JH) in rheumatoid arthritis (RA) patients and the relationship between JH and disease activity, hand functions, and quality of life. Methods: Thirty-four seropositive RA patients and 34 controls were included. Demographic data, body mass index, and state of JH (Beighton scores) of all participants were recorded. Two groups were compared in terms of JH. In RA patients, the Disease Activity Score-28 (DAS-28) was used to evaluate disease activity, the Duruöz Hand Index (DHI) for hand functions, and the Nottingham Health Profile (NHP) for quality of life. A correlation analysis was performed to evaluate the relationship of these data with JH in RA patients. Results: In the RA group, there were no patients with JH. No significant difference was found in the Beighton scores compared to the control group (p=0.383). The Beighton score showed a statistically significant negative correlation with DAS-28, DHI, NHP total, NHP pain, NHP physical activity, and NHP energy level. (p=0.026, p=0.015, p=0.003, p

"Seropositive Rheumatoid Arthritis With Axial Skeleton Involvement In A 17-year-old Female Athlete."

"Seropositive Rheumatoid Arthritis With Axial Skeleton Involvement In A 17-year-old Female Athlete."

Air Pollution and Rheumatoid Arthritis Risk and Progression: Implications for the Mucosal Origins Hypothesis and Climate Change for RA Pathogenesis.

The goal of this review paper is to summarize the main research and findings regarding air pollution and its association with the risk and progression of rheumatoid arthritis (RA). The most studied components of air pollution included particulate matter of ≤ 2.5 microns in diameter (PM2.5), PM10, carbon monoxide (CO), nitrogen dioxide (NO2), nitric oxide (NOx), sulfur dioxide (SO2), and ozone (O3). In addition, specific occupations and occupational inhalants have been investigated for RA risk. Several studies showed that increased exposure to air pollutants increased the risk of developing RA, particularly seropositive RA. There was evidence of gene-inhalant interactions for seropositive RA risk. Fewer studies have been conducted on RA disease activity and bone erosions. Some studies suggest that patients with RA-associated interstitial lung disease may have worse outcomes if exposed to air pollution. We summarized associations between air pollution and increased RA risk, including RA-associated interstitial lung disease. Relatively few studies investigated air pollution and RA disease activity or other outcomes. These results suggest an important role of air pollution for seropositive RA development and suggest that climate change could be a driver in increasing RA incidence as air pollution increases.

Anti-pentraxin 3 antibodies and residual disease activity in rheumatoid arthritis.

This study quantified anti-PTX3 antibodies in the serum of seropositive and seronegative rheumatoid arthritis (RA) patients, examining their associations with disease activity and patient-reported outcomes (PROMs). In this cross-sectional study, RA patients diagnosed per ACR/EULAR 2010 criteria were recruited. Seronegative RA was defined as ACPA < 7 kU/l. Data on demographics, clinical characteristics, medications, and PROMs were collected. Serum anti-PTX3 antibodies were measured using an in-house ELISA method. Comparative analyses were conducted with historical controls having psoriatic arthritis (PsA) and fibromyalgia (FM). The cohort included 83 RA patients (42 seropositive, 41 seronegative). Seropositive patients had lower anti-PTX3 antibody levels than PsA (p= 0.001) and FM (p= 0.004) controls. Seronegative patients had higher levels than seropositive ones (p= 0.032). Anti-PTX3 antibodies correlated with CDAI (r = 0.255), PtGA (r = 0.257), VAS-GH (r=-0.235), VAS-pain (r = 0.233), and HAQ (r = 0.311), but not with joint counts, inflammatory markers, or physician's global assessment. The PtGA association remained significant when adjusted for BMI, SJC28, ESR, and prednisone dosage (β = 0.206, p= 0.042). Patients with near-controlled RA (SJC28 ≤ 2, PtGA > 2) had higher anti-PTX3 levels than those with controlled disease (SJC28 ≤ 2, PtGA ≤ 2; p= 0.048). Tocilizumab or abatacept-treated patients had lower levels compared with those on TNFi or JAKi. Elevated anti-PTX3 antibodies in RA indicate residual active disease despite controlled inflammation. They may serve as a biomarker for true active disease, especially in seronegative RA patients who might be undertreated.

Heightened migraine risk in patients with rheumatoid arthritis: A national retrospective cohort study.

This study aimed to evaluate the association between rheumatoid arthritis (RA) and subsequent migraine risk using the Korean National Health Insurance Service database. Migraine may be related to immune dysfunction and previous studies have suggested an association with chronic inflammatory rheumatic diseases; however, the relationship between RA and migraine remains unclear. This was a population-based, nationwide, retrospective, longitudinal cohort study. Participants were enrolled from 2010 to 2017 and followed up until 2019. A total of 42,674 patients who had undergone a health checkup within 2 years prior to the initial diagnosis of RA were included in the study, after applying the exclusion criteria (previous migraine, other rheumatic disease, missing variables of interest). A non-RA control was obtained by age and sex-matching (1:5). Finally, 42,644 patients with RA were enrolled, with 213,370 individuals without RA included as controls. Among the patients with RA, 29,744 had seropositive RA (SPRA), and 12,900 had seronegative RA (SNRA). SPRA was defined by the International Classification of Diseases 10th revision (ICD-10) code M05, prescription of disease-modifying anti-rheumatic drugs (DMARDs), and enrollment in a special copayment reduction program. SNRA was defined by the ICD-10 code M06 and prescription of any DMARD. The primary endpoint was the occurrence of migraine incidents, defined using the ICD-10 code of migraine (G43). A total of 22,294 migraine cases (17,912/213,370 [8.3%] in controls and 4382/42,674 [10.2%] in RA) were reported during a mean follow-up of 4.4 years after a 1-year lag period. Patients with RA had a 1.2-fold higher risk of migraine compared with controls (adjusted hazard ratio [aHR] 1.21, 95% confidence interval [CI] 1.17-1.26). Increased risk of migraine was found in both patients with SNRA and SPRA compared with controls (aHR 1.20, CI 1.15-1.24 in SPRA; aHR 1.26, CI 1.19-1.34 in SNRA). Compared to patients with SNRA, those with SPRA did not demonstrate a heightened risk (aHR 0.94, CI 0.88-1.01). A significant interaction was confirmed between covariates (male, current smoker, those with diabetes mellitus, and dyslipidemia) and the risk of migraine (p for interaction of <0.05). RA was linked to a higher migraine risk, regardless of seropositivity.

Differential immunological profiles in seronegative versus seropositive rheumatoid arthritis: Th17/Treg dysregulation and IL-4.

Rheumatoid arthritis (RA) is an autoimmune disease with various subtypes. Among these, seronegative rheumatoid arthritis (SnRA), distinguished by its distinctive seronegative antibody phenotype, presents clinical diagnosis and treatment challenges. This study aims to juxtapose the immunological features of SnRA with seropositive rheumatoid arthritis (SpRA) to investigate potential mechanisms contributing to differences in antibody production. This study included 120 patients diagnosed with RA and 78 patients diagnosed with psoriatic arthritis (PsA), comprising 41 cases of SnRA and 79 cases of SpRA. Clinical, serological, and immune data were collected from all participants to systematically identify and confirm the most pivotal immunological distinctions between SnRA and SpRA. (1) SpRA demonstrates more pronounced T-helper 17 cells (Th17)/Regulatory T cells (Treg) dysregulation, vital immunological differences from SnRA. (2) SpRA exhibits higher inflammatory cytokine levels than SnRA and PsA. (3) Lymphocyte subset ratios and cytokine overall distribution in SnRA close to PsA. (4) Interleukin-4 (IL-4) emerges as the central immunological disparity marker between SnRA and SpRA. Th17/Treg imbalance is one of the vital immunological disparities between SnRA and SpRA. Interestingly, PsA and SnRA display similar peripheral blood immunological profiles, providing immunological evidence for these two diseases' clinical and pathological similarities. Furthermore, IL-4 emerges as the central immunological disparity marker between SnRA and SpRA, suggesting its potential role as a triggering mechanism for differential antibody production.

Drug retention of biologic and targeted synthetic disease-modifying antirheumatic drugs in Korean patients with seropositive rheumatoid arthritis.

The aim of this study was to compare the short- and long-term retention rates of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in Korean patients with seropositive rheumatoid arthritis. This study was conducted with 1,538 treatment courses of 1,063 patients, including adalimumab (n = 332), etanercept (n = 369), infliximab (n = 146), abatacept (n = 152), tocilizumab (n = 299), tofacitinib (n = 136), and baricitinib (n = 104), in patients with seropositive rheumatoid arthritis who started b/tsDMARD treatment between 2008 and 2020 at Seoul St. Mary's Hospital. Discontinuation 1 and 3 years after the first prescription of each drug was investigated. Kaplan- Meier estimates of time to discontinuation were calculated to compare the difference in drug retention rate for each drug. Patient-level predictors of drug discontinuation were evaluated using a Cox proportional hazards model. The overall 1-year drug retention rate was from 60.1% for adalimumab to 90.0% for tofacitinib in the b/tsDMARD-naïve group, and from 55.2% for infliximab to 84.8% for tofacitinib in the b/tsDMARD-experienced group. The 3-year drug retention rate was from 36.9% for infliximab to 86.5% for tofacitinib in the b/tsDMARD-naïve group, and from 31.0% for infliximab to 65.4% for tocilizumab in the b/tsDMARD-experienced group. Drug discontinuation appeared to be affected by specific types of b/tsDMARDs. Tocilizumab and tofacitinib are less commonly discontinued compared to tumor necrosis factor-α inhibitors at 1 and 3 years. Specifically, tofacitinib in the b/tsDMARD-naïve group and tocilizumab in the b/tsDMARD-experienced group showed the highest 3-year retention rates.

Association of X-ray disease stage with basic patient data, laboratory values and treatment modalities in patients with seropositive rheumatoid arthritis

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Aim&amp;lt;/strong&amp;gt; To investigate whether the radiographic progression of rheumatoid arthritis (RA) correlates with inflammatory markers and other laboratory values, and its association with treatment modalities.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Methods&amp;lt;/strong&amp;gt; This observational study included 125 patients with seropositive RA. Data were obtained from patients&amp;amp;rsquo; medical records from the year of 2022. Inclusion criteria were patients with seropositive RA who had attended follow-up with a rheumatologist. Basic patient data were collected: gender, age, duration of RA, hospital admission, systolic and diastolic blood pressure, and X-ray stage of RA. Stages of RA are defined by the American College of Rheumatology and they ranged from stage 1, which represents no de-structive changes on X-ray, up to stage 4 where bony or fibrous ankylosis is present.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Results&amp;lt;/strong&amp;gt; There were no differences in X-ray stages of RA between genders. Patients with a higher X-ray stage were younger and had a longer duration of illness. Patients in stages III and IV had higher systolic blood pressure (BP), patients in stage IV had higher diastolic BP. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were higher in X-ray stages II-IV compared to stage I. The patients treated with methotrexate had higher radio-graphic stages.&amp;amp;nbsp;&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Conclusion&amp;lt;/strong&amp;gt; X-ray changes can be associated with CRP and ESR levels, since structural damage is related to RA disease activity and functional disability. The use of newer treatment modalities may be required to stop the radiographic progression of RA.&amp;lt;/p&amp;gt;

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.

Time to start disease modifying drugs for adults with seropositive rheumatoid arthritis: results of the first year of the national New Zealand Rheumatology Association (NZRA) audit.

This audit describes variation in the time from referral to starting disease modifying drug (DMARD) for people with newly diagnosed seropositive rheumatoid arthritis (RA), how frequently this was within the recommended 6 weeks and whether regional, service-level or patient-level factors were associated with this variation. Rheumatologists submitted data on new patients with a new diagnosis of rheumatoid factor and/or cyclic-citrullinated peptide antibody positive RA. The association between visit funding, ethnicity, socio-economic deprivation, rurality, local specialist staffing levels and the time to DMARD treatment was assessed using Cox proportional-hazard models. Data were collected on 355 patients over 12 months. Overall, 64.8% of patients commenced DMARD treatment within 6 weeks of referral and this was associated with rheumatologist FTE per 100,000 population (adjusted HR 2.47, 95%CI 1.27-4.81; p=0.008) and the rurality (Geographic Classification of Health [GCH]) of the patient (for R2 compared to U1 adjusted HR 0.20, 95%CI 0.09-0.43; p<0.001). There was no association between time to DMARD and ethnicity or socio-economic deprivation. There was significant variation in time to DMARD treatment, mainly related to variation in rheumatologist staffing levels and patient rurality. Rheumatologist staffing levels of 1.0 FTE/100,000 population was associated with 80% of patients meeting the recommended 6-week time to DMARD treatment.

Anti-CCP Antibodies in Unaffected First-Degree Relatives of Rheumatoid Arthritis Patient

Introduction: Rheumatoid arthritis (RA) is perhaps the most common inflammatory arthritis, affecting 0.5% to 1% of the general population worldwide. Environmental and genetic influences are important risk factors for pathogenesis of RA. First-degree relatives (FDRs) of RA patients sharing genetic and environmental risk factors for RA may represent as pre-RA state. Since anti-CCP antibody appears years before the onset of RA, it can be used to estimate risk-potential for future development of RA in unaffected FDRs of RA patient. Objective: To see the serum anti-CCP antibody in unaffected FDRs of RA patients. Materials and Methods: This cross-sectional study was conducted from July 2019 to June 2020 in Department of Biochemistry, Dhaka Medical College, Dhaka. A total number of 50 subjects were selected among which 25 were unaffected FDRs of RA patients and the other 25 were age &amp; gender matched healthy subjects. The related RA patients were selected from Rheumatology outdoor, Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka and the healthy subjects were taken from the attendants came to the same institute who did not have RA patient in their family. The key variables (age and gender) were recorded and outcome variable (anti-CCP antibody in study subjects) was estimated. Statistical analysis was done by SPSS 26.0 and the significance was defined as p &lt; 0.05. Results: Mean age of the FDRs of RA patient was 31.36 ± 10.51 years and that of healthy subjects was 31.56 ± 8.89 years. Most of the participants were in age group 20-29 years followed by 30-39 years. 4% of FDRs of RA patient were anti-CCP antibody positive and no positive case was recorded in healthy subjects. The median level of anti-CCP antibody in FDRs of RA patient was 0.50 U/mL and that in healthy subjects was 0.09 U/mL. The level of significance (p = 0.002) showed that serum anti-CCP antibody level was significantly higher (within normal range) in FDRs of RA patient than in healthy subjects, which was even more significant in FDRs of seropositive RA patients. Conclusion: This study revealed that serum anti-CCP antibody level was significantly higher (within normal range) in FDRs of RA patient than in healthy subjects and the proportion of positive anti-CCP antibody was more in FDRs of RA patient than in healthy subjects. Medicine Today 2024, Vol.36 (2): 76-81

Multimodal nature of pain syndrome in patients with rheumatoid arthritis in relation to the course of the disease and clinical characteristics

Purpose of the study. To evaluate the character of pain syndrome in patients with rheumatoid arthritis in correlation with the course of the disease and comorbid pathology.Material and methods. Sixty-six patients with a verified diagnosis of RA were examined. Of them 84.9% were women (n=56) and 15.1% men (n=10). The median age was 59 [52; 63] years. Disease activity was assessed by DAS28-CRP, with a median of 5.2 [4.54; 6.0]. Patients with moderate (31.8%) and high activity (57.5%) predominated. Disease duration averaged Me 156 [93; 246] months. Seropositive RA was suffered by 89.3% of patients. The distribution by radiological stage was as follows: 2 radiological stage – 36.3% (n=24), 3 radiological stage – 30.3% (n=20), 4 radiological stage – 33.4% (n=22). Baseline anti-inflammatory therapy was taken by 84.8% of patients (n=56), genetically engineered biological drugs were received by 28.7% (n=16). To assess the multicomponent nature of pain syndrome, the following were used: Pain Detect questionnaire — to verify neuropathic pain (NP), CSI questionnaire — to verify central sensitisation (CS). The EQ-5D-3L questionnaire was used to assess quality of life, and the Charlson index was used to assess comorbid pathology. Structural changes were assessed by modified Sharpe method on hand and foot radiographs, synovium vascularisation was assessed by joint ultrasound.Results. 84.8% of patients had pain syndrome of mixed nature. NP correlated with pain intensity by VAS (rSp=0.458, p&lt;0.001), DAS28-CRP (rSp=0.509, p&lt;0.001), number of peripheral arthritis (rSp=0, 414, p&lt;0.001), number of comorbidities (rSp=0.337, p=0.006), Charlson index (rSp=0.323, p=0.009), EQ-5D-3L (rSp= –0.268, p=0.031). CS–with VAS pain intensity (rSp=0.250, p=0.045), DAS28-CRP (rSp=0.251, p=0.044), number of painful joints (rSp=0.353, p=0.004), number of comorbidities (rSp=0.368, p=0.003), BMI (rSp=0.266, p=0.032), systolic blood pressure level (rSp=0.403, p&lt;0.001), number of erosions on hand and foot radiographs (rSp= –0.299, p=0.016), EQ-5D-3L (rCp= –0.408, p&lt;0.001). Patients with the presence of synovial vascularization by ultrasound had three-component pain in more than half of cases, and the combination of inflammatory pain and CS did not occur in them.Conclusions. 84.8% of patients had multicomponent pain, with pain associated only with clinical parameters of disease activity. Associated pathology and local chronic inflammation in the joint potentiate the development of other types of pain and have a mutual negative influence.

Incidence of seropositive and seronegative rheumatoid arthritis in Denmark: a nationwide population-based study

Objective To investigate and compare trends in incidence rates (IRs) of seropositive and seronegative rheumatoid arthritis (RA) in Denmark using various data sources for serostatus definition. Method 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. Results 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. Conclusions 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.

Impact of anti-human IgG hinge peptide antibodies on identification of patients with early seronegative rheumatoid arthritis.

The early diagnosis of seronegative rheumatoid arthritis (SNRA), characterised by the absence of rheumatoid factor and anti-citrullinated antibody, involves a greater challenge compared to seropositive RA (SPRA). This study aimed to assess the discriminatory potential of anti-human IgG hinge antibodies (AHAs) for patients with early SNRA. DMARDs-naive patients with SPRA (n=43), SNRA (n=21), and non-RA (n=49), with disease duration < 2 years, were included. Antigens comprised IgG1 or IgG4 F(ab')2 cleaved by pepsin or MMP-3 and their hinge peptide analogues. Eight IgG anti-hinge antibodies (AHAs) against these antigens were measured in sera from the patients and 58 healthy controls (HCs) using ELISA. Serum CRP and MMP-3 levels, and clinical disease activity index (CDAI), were obtained from medical records. The area under the curve (AUC) obtained from logistic regression and receiver operating characteristic curve analyses were used as a discriminant indicator. The levels of the IgG AHAs were as follows: SPRA≥SNRA≈non-RA>HC. None of the AHAs were effective in discriminating SNRA from non-RA. However, the combination of MMP-3 and AHAs against IgG4 hinge peptide analogues demonstrated the utility (AUC=0.94). Furthermore, combination of MMP-3, AHAs against IgG1 hinge peptide analogues and CDAI maximally exerted discriminatory power (AUC=0.997). Specific AHAs in combination with MMP-3 and CDAI are potentially useful to discriminate SNRA from non-RA.

Rheumatoid neutrophilic dermatitis: A case report and review of the literature

AbstractRheumatoid neutrophilic dermatitis (RND) is a dermatological condition typically associated with rheumatoid arthritis (RA). The low prevalence of RND and the wide spectrum of its possible clinical appearances make the diagnosis challenging. Current literature is still lacking a comprehensive overview of this rare cutaneous disorder. The aim of this review is to summarize data from the existing literature on RND, focusing on its epidemiology, clinical manifestations, histopathology and treatment. Hence, a comprehensive literature search of case reports and series was made, starting from a Medline (via PubMed) and Scopus databases. We also included in the analysis one patient attending to our dermatology department and diagnosed with RND. Overall, 54 cases of RND were identified. The majority of patients were female (72.3%) with a median (IQR) age at the time of diagnosis of 58 (65‐45) years. RND followed the onset of RA in 87% of patients with an average (SD) latency time of approximately 10 (8.9) years. In 1 (1.8%) case the dermatitis preceded the appearance of joint symptoms, while in three (5.5%) cases it occurred concomitantly with them. Seropositive RA was the major associated form (76.5%). Clinically, asymptomatic papules (31%), nodules (15.1%) and/or plaques (13.5%) distributed bilaterally on extremities were most frequently described. Notably, females were more prone to develop a painful dermatitis (84.6%) compared to males. The vesicobullous (12.7%) and pustular (9.2%) clinical subtypes were the most demonstrative in contrast to the urticarial skin manifestations and the potential figurative/annular distribution of the lesions. Spontaneous resolution of RND was rare (5.5%). Systemic treatments, mainly represented by steroids and anti‐neutrophilic agents (dapsone, colchicine), were consistently required.

Acetylated bacterial proteins as potent antigens inducing an anti-modified protein antibody response

ObjectiveGut-residing bacteria, such as Escherichia coli, can acetylate their proteome under conditions of amine starvation. It is postulated that the (gut) microbiome is involved in the breach of immune tolerance...

Minor Genetic Overlap Among Rheumatoid Arthritis, Myocardial Infarction, and Myocardial Infarction Risk Determinants.

The aim of this study was to investigate whether a shared genetic susceptibility exists between individuals with rheumatoid arthritis (RA) and individuals with myocardial infarction (MI)-including major MI risk factors-and to quantify the degree of any such overlap. Genome-wide association study (GWAS) data for individuals with RA were constructed from a sample of 26,637 Swedish patients with RA and controls without RA. For patients with MI, GWAS data were obtained from a previously published meta-analysis. Genome-wide genetic correlation was estimated via linkage disequilibrium score regression. LAVA was employed to estimate local genetic correlations in ~2,500 nonoverlapping loci, including the major histocompatibility complex. The controls without RA were used for reference panel data. We also assessed stratified estimates of both genome-wide and local genetic correlation based on subsamples of individuals with seropositive RA and those with seronegative RA. Furthermore, genome-wide genetic correlation was estimated between RA and selected cardiovascular risk factors to elucidate pleiotropic relationships. Following quality control, our GWAS of patients with RA consisted of 25,826 individuas. Genome-wide genetic correlation between patients with RA and MI was estimated to 0.13 (95% confidence interval -0.03 to 0.29). Six regions exhibited significant local genetic correlation, though none harbored any known risk single-nucleotide polymorphisms for either of the two traits. Estimates were similar in both individuals with seropositive RA and those with seronegative RA. No statistically significant genetic correlations were observed between RA risk factors and any of the MI risk factors. Our findings indicate that genetic overlap between patients with RA and MI is minor. Furthermore, genetic overlap between RA and MI risk factors seem unlikely to provide a major contribution to the increased risk of MI observed in patients with RA.

Evaluation of polygenic scoring methods in five biobanks shows larger variation between biobanks than methods and finds benefits of ensemble learning

Methods of estimating polygenic scores (PGSs) from genome-wide association studies are increasingly utilized. However, independent method evaluation is lacking, and method comparisons are often limited. Here, we evaluate polygenic scores derived via seven methods in five biobank studies (totaling about 1.2 million participants) across 16 diseases and quantitative traits, building on a reference-standardized framework. We conducted meta-analyses to quantify the effects of method choice, hyperparameter tuning, method ensembling, and the target biobank on PGS performance. We found that no single method consistently outperformed all others. PGS effect sizes were more variable between biobanks than between methods within biobanks when methods were well tuned. Differences between methods were largest for the two investigated autoimmune diseases, seropositive rheumatoid arthritis and type 1 diabetes. For most methods, cross-validation was more reliable for tuning hyperparameters than automatic tuning (without the use of target data). For a given target phenotype, elastic net models combining PGS across methods (ensemble PGS) tuned in the UK Biobank provided consistent, high, and cross-biobank transferable performance, increasing PGS effect sizes (β coefficients) by a median of 5.0% relative to LDpred2 and MegaPRS (the two best-performing single methods when tuned with cross-validation). Our interactively browsable online-results and open-source workflow prspipe provide a rich resource and reference for the analysis of polygenic scoring methods across biobanks.