Anti-citrullinated Peptide Antibodies Research Articles

Rheumatoid arthritis disease activity significantly impacts on the severity of interstitial lung disease

ObjectivesRheumatoid arthritis (RA) related interstitial lung disease (ILD) impacts on the treatment strategy and its prognosis in patients with RA. However, the relationship between RA disease activity and the severity of comorbid ILD has not been fully investigated. This study aimed to investigate the impact of RA disease activity on the severity of comorbid ILD in detail based on currently established visual scoring method along with physiological severity.MethodsConsecutive patients with RA visiting to our Rheumatology Centre between December 2020 and December 2023 were analysed. The radiological severity of ILD was evaluated by averaging the extent of the combined lesion of ground glass opacity, reticulation and honeycombing in 5% increments in six representative high-resolution computed tomography slices ranging from 0% (no involvement) to 100% (all lung fields affected) according to Goh and Walsh’s method. Associations between the radiological and physiological severity of ILD and patients’ features were investigated using linear regression analysis.ResultsAmong 124 patients (32 men, 92 women), the median age was 70 years, and the median disease duration was 2.92 years. Radiological severity of ILD was 0% (without ILD) in 107 (86.2%), ILD with extent < 10% in nine (7.2%), ILD with extent ≥10% and < 20% in three (2.4%), ILD with extent ≥20% in five (4.0%). Both disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) (standardized coefficient = 0.199, P = 0.03) and rheumatoid factor titre (standardized coefficient = 0.247, P = 0.01) were significantly associated with the radiological quantitative severity of ILD in multivariate analysis adjusted for age, sex, disease duration, smoking status and anti-citrullinated peptide antibody titre. DAS28-ESR was significantly associated with forced vital capacity% predicted (standardized coefficient = -0.230, P = 0.047).ConclusionsDisease activity of RA was significantly associated with the severity of RA-ILD both radiologically and physiologically.

Exhaled Nitric Oxide Reflects the Immune Reactions of the Airways in Early Rheumatoid Arthritis.

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

Tumor necrosis factor alpha induced protein 3, interleukin 10, tumor necrosis factor alpha, and interleukin 17F genes polymorphisms in Algerian patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation. Its pathogenesis involves immunological, genetic, and environmental factors. We investigate the association between Tumor Necrosis Factor α Protein 3 (TNFAIP3), Interleukin 10 (IL10), Tumor Necrosis Factor α (TNF α), and Interleukin 17F (IL17F) polymorphisms with susceptibility to RA. 191 patients with RA diagnosed according to the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification and 190 healthy subjects were recruited. Rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), and C-reactive protein (CRP) were measured. Genotyping of the polymorphisms was performed by real-time PCR. Analysis of the allelic frequencies of TNFAIP3 showed a positive association OR (95% CI) = 1.46 (1.01-2.09); p = 0.04, but failed to meet the criteria of significance after Bonferroni Correction. The genotypic and allelic distribution of the IL10, IL17F, and TNFα showed no significant difference when comparing the RA group with controls. Furthermore, the genotype codominant model shows a moderate positive association in the presence of ACPA (OR (95% CI) = 2.82 (1.22-6.24); p = 0.01. None of the polymorphisms studied was associated with RF and CRP production. Our results show that there is a tendency for the AG genotype of IL10-1082 to be associated with the production of ACPA in patients with RA. None of the variants studied were associated with RA susceptibility in Algerians.

SPECIFIC BIOCHEMICAL INDICATORS AND INFLAMMATORY MARKERS IN RHEUMATOID ARTHRITIS (RA)

It is acknown that Rheumatoid inflammation is a chronic systemic autoimmune disease developing on the background of infection. Damages mainly the heart, blood vessels, musculoskeletal system and other internal organs. Multiple joints may be affected, primarily the knee, ankle and elbow undergoing destruction leads to pain, mainly symmetrical. Damaged joints swollen and skin in these foci reddens; joint morning stiffness lasts for an hour or more, this sign is accompanied by low fever and fatigue. As a result of the rheumatic process, the heart is damaged, leading to cardiovascular manifestations. Analysis of blood parameters allows the severity of the disease to be determined based on a relatively new method using Das28. The obtained results for ESR and CRP are used to calculate DAS28, which also allows monitoring of RA treatment. Most patients with rheumatoid arthritis (RA) are seropositive—they have abnormally high levels of rheumatoid factor (RF) or anti-citrullinated peptide antibodies (anti-CPP) in the blood. The article examines aspects of synthetic, chemical and alternative medicine impact on treating patients with RA as well. The article discusses comparative aspects of pharmacological and herbal medicine in the therapeutics. According to the literature, patients who have not received the expected results after treatment with pharmacological preparations successfully use herbal remedies as a means of body restoring and healing. To date, the success of traditional medicine is ahead of those of conventional using synthetic drugs.

Pathophysiology, diagnosis, and herbal medicine-based therapeutic implication of rheumatoid arthritis: an overview.

Rheumatoid arthritis (RA) stands as an autoimmune disorder characterized by chronic joint inflammation, resulting in profound physiological alterations within the body. Affecting approximately 0.4-1.3% of the global population, this condition poses significant challenges as current therapeutic approaches primarily offer symptomatic relief, with the prospect of complete recovery remaining elusive. This review delves into the contemporary advancements in understanding the pathophysiology, diagnosis, and the therapeutic potential of herbal medicine in managing RA. Notably, early diagnosis during the initial stages emerges as the pivotal determinant for successful recovery post-treatment. Utilizing tools such as Magnetic Resonance Imaging (MRI), anti-citrullinated peptide antibody markers, and radiography proves crucial in pinpointing the diagnosis of RA with precision. Unveiling the intricate pathophysiological mechanisms of RA has paved the way for innovative therapeutic interventions, incorporating plant extracts and isolated phytoconstituents. In the realm of pharmacological therapy for RA, specific disease-modifying antirheumatic drugs have showcased commendable efficacy. However, this conventional approach is not without its drawbacks, as it is often associated with various side effects. The integration of methodological strategies, encompassing both pharmacological and plant-based herbal therapies, presents a promising avenue for achieving substantive recovery. This integrated approach not only addresses the symptoms but also strives to tackle the underlying causes of RA, fostering a more comprehensive and sustainable path towards healing.

Machine learning-based prediction of rheumatoid arthritis with development of ACPA autoantibodies in the presence of non-HLA genes polymorphisms.

Machine learning (ML) algorithms can handle complex genomic data and identify predictive patterns that may not be apparent through traditional statistical methods. They become popular tools for medical applications including prediction, diagnosis or treatment of complex diseases like rheumatoid arthritis (RA). RA is an autoimmune disease in which genetic factors play a major role. Among the most important genetic factors predisposing to the development of this disease and serving as genetic markers are HLA-DRB and non-HLA genes single nucleotide polymorphisms (SNPs). Another marker of RA is the presence of anticitrullinated peptide antibodies (ACPA) which is correlated with severity of RA. We use genetic data of SNPs in four non-HLA genes (PTPN22, STAT4, TRAF1, CD40 and PADI4) to predict the occurrence of ACPA positive RA in the Polish population. This work is a comprehensive comparative analysis, wherein we assess and juxtapose various ML classifiers. Our evaluation encompasses a range of models, including logistic regression, k-nearest neighbors, naïve Bayes, decision tree, boosted trees, multilayer perceptron, and support vector machines. The top-performing models demonstrated closely matched levels of accuracy, each distinguished by its particular strengths. Among these, we highly recommend the use of a decision tree as the foremost choice, given its exceptional performance and interpretability. The sensitivity and specificity of the ML models is about 70% that are satisfying. In addition, we introduce a novel feature importance estimation method characterized by its transparent interpretability and global optimality. This method allows us to thoroughly explore all conceivable combinations of polymorphisms, enabling us to pinpoint those possessing the highest predictive power. Taken together, these findings suggest that non-HLA SNPs allow to determine the group of individuals more prone to develop RA rheumatoid arthritis and further implement more precise preventive approach.

Relationship between Different Hematological Parameters and Disease Activity in Patients with Rheumatoid Arthritis

Background and objectives: Rheumatoid arthritis is a type of immune disorder that has an impact on the entire body. The objective was to measure and compare various hematological parameter values between chronic and new cases also in new patients who exhibited varying degrees of disease activity. Methods: This study was a cross-sectional survey, conducted in Rizgary Hospital and private clinics in Erbil city/ Kurdistan Region of Iraq. Two groups each of 30 patients; with newly diagnosed the 2010 ACR/EULAR criteria are divided into four groups, each of which has a point score: joint symptoms, serology (including Rheumatoid factor and/or Anti-Citrullinated Peptide Antibody), duration of symptoms (less than or more than 6 weeks), and acute-phase reactants (c-reactive protein and/or erythrocyte sedimentation rate) and chronic Rheumatoid Arthritis cases enrolled in this study from October 2021 till September 2022. Hematological parameter and disease activity monitored and compared between both groups, in addition to comparison between cases in the same group. Results: The majority (81.7%) of patients were female and (18.3%) of them were male, mean age ± std. deviation of respondents was 48.80 ± 9.13 years. There was significant statistical association between study groups and joint swelling, multiple or single joint and disease activity (DAS 28), also, the difference between both groups was statistically significant regarding mean pain score, white blood cells, serum folate, and rheumatoid factor. Likewise; the association was significant between study groups and multiple or single joint. There was significant statistical association between study groups and DAS 28, the majority (86.7%) of newly diagnosed patients had low – moderate level of DAS 28 while 40% of chronic subjects measured high level of DAS 28. Conclusion: Hematological markers including disease activity score, white blood cells, serum folate, C-reactive protein and rheumatoid factor were good indicators for measurement of rheumatoid arthritis severity and activity in the selected sample of patients.

Rheumatoid Arthritis and Pericardial Effusion - A Unique Major Manifestation.

Pericardial effusion is common in the setting of rheumatoid arthritis (RA); however, it is rarely its first manifestation. An 82-year-old male presented with abdominal pain, vomiting and fever. Blood analysis revealed elevated systemic inflammatory markers, and an abdominal computed tomography scan revealed non-specific alveolar condensation of the right pulmonary base and pericardial effusion subsequently quantified as medium size by transthoracic echocardiography. A large aetiological panel was requested, with the autoimmunity study revealing high levels of rheumatoid factor (RF) and anti-citrullinated cyclic peptide (anti-CCP) antibodies. Since the patient did not present articular involvement, the initial hypothesis was pericardial effusion due to pneumonia and no specific treatment for RA was started. At follow-up, the pericardial effusion recurred and a pericardiocentesis was performed. The pericardial fluid analysis was sterile, and no malignant cells were identified. A new serological study confirmed high levels of RF and anti-CCP antibodies, and immunomodulatory treatment was initiated. After one year, the pericardial effusion recurred due to non-compliance with immunomodulatory therapy. A surgical pleuro-pericardial window was performed, and the cytological study of the pericardial patch revealed submesothelial thickening and foci of perivascular lymphocytic infiltrate. The patient remained asymptomatic. After exclusion of a large spectrum of infectious and non-infectious causes and the relapse after suspension of immunomodulatory treatment, the most probable aetiology for the pericardial effusion remains RA. Pericardial syndromes can be the first manifestation of AR even in the absence of articular symptoms and this disease must be considered in the aetiological investigation. The occurrence of pericardial effusion in the setting of rheumatoid arthritis (RA) is a usual finding but this form of extra-articular manifestation is possibly the first and only presentation of the disease.In the case of recurrent pericardial effusion, the diagnosis of RA must be considered in the aetiological investigation even in the absence of more common manifestations of the disease.

A potential role for chlamydial infection in rheumatoid arthritis development

Abstract Objectives To assess the relationship between self-reported and serological evidence of prior chlamydial infection, rheumatoid arthritis (RA)-related autoantibodies and risk of RA development. Methods This is a nested study within a prospective Swiss-based cohort including all first-degree relatives of RA patients (RA-FDR) who answered a questionnaire on past chlamydial infections. Primary outcome was systemic autoimmunity associated with RA (RA autoimmunity) defined as positivity for anti-citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF). Secondary outcomes were high levels of RA autoimmunity, RA-associated symptoms and RA autoimmunity, and subsequent seropositive RA diagnosis. We conducted a nested case–control analysis by measuring the serological status against the major outer membrane protein of Chlamydia trachomatis. We replicated our analysis in an independent USA-based RA-FDR cohort. Results Among 1231 RA-FDRs, 168 (13.6%) developed RA autoimmunity. Prevalence of self-reported chlamydial infection was significantly higher in individuals with RA autoimmunity compared with controls (17.9% vs 9.8%, odds ratio [OR] = 2.00; 95% CI: 1.27, 3.09; P &amp;lt; 0.01). This association remained significant after adjustments (OR = 1.91; 95% CI: 1.20, 2.95). Stronger effect sizes were observed in later stages of RA development. There was a similar trend between a positive C. trachomatis serology and high levels of RA autoimmunity (OR = 3.05; 95% CI: 1.10, 8.46; P = 0.032). In the replication cohort, there were significant associations between chlamydial infection and RF positivity and incident RA, but not anti-CCP positivity. Conclusion Self-reported chlamydial infections are associated with elevated RA autoimmunity in at-risk individuals. The differing association of chlamydial infections and ACPA/RF between cohorts will need to be explored in future studies, but is consistent with a role of mucosal origin of RA-related autoimmunity.

Serum calprotectin correlates more strongly with inflammation and disease activity in ACPA positive than ACPA negative rheumatoid arthritis.

The aim of the present study was to evaluate performance of serum and synovial fluid levels of the granulocyte protein calprotectin as inflammatory biomarker in rheumatoid arthritis (RA) patients with knee synovitis. 76 RA patients with ongoing knee synovitis were included. Data on disease activity score with 28 joints and their subcomponents and radiological destruction of the affected knee were collected. White blood cell count, C-reactive protein, anti-citrullinated peptide antibodies (ACPA) against cyclic citrullinated peptide version 2 (anti-CCP2), IgM rheumatoid factor (RF) and calprotectin were analysed in parallel in circulation and in synovial fluid (SF). Counts of polynuclear and mononuclear cells were measured in SF. Serum (S) calprotectin correlated stronger than SF-calprotectin with inflammatory markers and disease activity. Instead, SF-calprotectin showed a strong correlation to SF counts of white blood cells, and especially to polymorphonuclear cell counts (Spearman's rho = 0.72, p< 0.001). S-calprotectin showed markedly stronger correlation with inflammatory markers and disease activity in ACPA positive as compared with ACPA negative RA patients; a similar difference was observed for patients with and without IgM RF. The particularly strong association between circulating calprotectin and inflammation in ACPA positive RA is a new argument for a specific role for polymorphonuclear granulocytes/neutrophils in this RA subset. Measurement of calprotectin in SF does not convey any additional benefit compared with measurement in the circulation in RA patients with knee synovitis.

Recurrent ACPA-positive pericarditis, would it be a pre-clinical manifestation of RA?

Abstract Introduction Rheumatoid arthritis (RA) is a chronic inflammatory rheumatic disease with an autoimmune component that preferentially affects the small joints of the hands and feet. Extra-articular manifestations may be associated with it. These are rather long-term complications compared to the inaugural forms of the disease. Observation We report the observation of a 62-year-old female patient with a history of high blood pressure under monotherapy by a conversion enzyme inhibitor, followed for recurrent pericarditis for three years, who was initially treated with anti-bacillary drugs without improvement. She presented two years ago an episode of pericarditis of great abundance requiring a pericardial drainage. The pericardial biopsy was non-specific. The etiological work-up revealed the presence of anti-citrullinated peptide antibodies (ACPA) and a rheumatoid factor (RF) at very high levels. The patient did not present any other systemic signs, especially articular ones. Joint imaging was normal. The evolution was marked by the persistence of a pericardial effusion of a small to medium size. RA could not be retained according to the American College of Rheumatology/ European League Against Rheumatism’s (ACR/EULAR) 2010 criteria. Glucocorticoids therapy at a dose of 0.5 mg/kg/day allowed the resolution of the pericarditis without recurrence, with a six-month follow-up period. Conclusion This is an extra-articular manifestation that would be inaugural of RA. It is an atypical presentation in the usual history of the disease. The inclusion of extra-articular involvement in the classification criteria and in the groups at risk of developing RA would be useful in these cases.

In early rheumatoid arthritis, anticitrullinated peptide antibodies associate with low number of affected joints and rheumatoid factor associates with systemic inflammation

ObjectivesTo investigate how individual rheumatoid arthritis (RA) autoantibodies associate with individual signs and symptoms at the time of RA diagnosis.MethodsIgA, IgG, IgM rheumatoid factor (RF), antibodies against cyclic citrullinated peptide...

Factors associated of long-term retention rate of Janus kinase inhibitors in a multi-failure rheumatoid arthritis population.

We aimed to retrospectively evaluate retention rate and causes of discontinuation of JAKi in RA patients with particular regards to difficult-to-treat subgroups. The diffusion of Janus kinase inhibitors (JAKi) for the treatment of rheumatoid arthritis (RA) has rapidly increased in recent years due to their effectiveness, even in difficult-to-treat subgroups of patients. After the publication of the Oral Surveillance study, the labelling of JAKi was modified, advising against their use in elderly patients and those at risk for cardiovascular events and malignancies. Demographic, clinical, serological and therapeutic characteristics of RA patients treated with JAKi were recorded, including smoking habit and comorbidities. Three hundred and thirty consecutive RA patients were enrolled in the study. Among them, 50.3% patients had previously failed at least two biologic DMARDs. Risk factors for the use of JAKi were reported in 75.5% of patients, 41.5% of them were older than 65 years, 37.6% had smoked, while 48.8% had increased cardiovascular or cancer risk. Anticitrullinated peptide antibodies (ACPA) and combination therapy with conventional synthetic DMARDs were associated with a longer drug persistence and ACPA remained independently associated to a higher retention rate of JAKi also in the subgroup of difficult-to-treat patients. In conclusion, our study supports the clinical effectiveness of JAKi in RA, even in the multi-failure subgroup of patients, where the risk/benefit ratio overcomes the safety risk. The presence of ACPA and the concurrent use of + cs-DMARD may increase the survival on JAKi in the long term.

Interstitial lung disease in patients with rheumatoid arthritis: a narrative review

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease of unknown origin. Although it mainly affects joints, it can have extra-articular manifestations, with the lung being one of the most affected organs. The estimated incidence of diffuse interstitial lung disease (ILD) is 4 cases to 4.5 cases/1000 patient-years. The most common forms are usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP; 44–46% and 33–44%, respectively), although there have been reports of cases involving all the histopathologic forms described for the disease. RA-ILD is associated with specific risk factors, such as male sex, older age, smoking, and positive rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA) levels. The clinical course of ILD ranges from asymptomatic forms to rapidly progressive disease in a minority of cases. It has been estimated that the risk of death is up to 3-fold higher in patients with RA-ILD than in those without ILD, making RA-ILD the second most common cause of death after cardiovascular disease. Treatment of RA has improved considerably in recent years with the advent of biologics; however, the use of these agents has been restricted in patients with ILD owing to safety concerns. Many doubts continue to surround the treatment of patients with RA-ILD. Therefore, the objective of this review is to examine the current management of affected patients in terms of diagnosis, treatment, and follow-up.

Frequency of fimA Genotypes of P. gingivalis in Rheumatoid Arthritis Patients and Control group.

Rheumatoid arthritis (RA): Chronic inflammatory polyarthritis, an autoimmune response targeting citrullinated antigens, due to destructive synovial joint inflammation. Porphyromonas gingivalis, a gram-negative bacterium residing in the subgingival tissues of the oral cavity, has been implicated in the association with RA, mainly due to the identification of a bacterial enzyme known as peptidyl arginine deaminase (PAD). The presence of this enzyme in P. gingivalis suggests its potential role in RA development by generating citrullinated antigens. Aims: The association between P. gingivalis and the development of anticitrullinated peptide antibody (ACPA) and if its role as an environmental risk factor of RA. Methods: This case-control study involved a total 140 participants, collection of blood and gingival crevicular fluid (GCF) samples from the participants, various tests were conducted, Specific PCR primers targeting fimA genotypes of P. gingivalis were utilized to amplify the relevant genetic regions.Statistical analysis used: Statistical Package for the Social Sciences (SPSS) version 26, a T-test and Chi-square (χ^2) test were utilized. Results: The p-values for ESR, ACCP, and IL-17 were 0.0001, 0.02, and 0.0001, respectively, indicating strong statistical significance for RA patients. Among the RA patients with P. gingivalis infection and the RA patients without P. gingivalis infection the analysis did not reveal a statistically significant difference in mean of ACCP and all biomarkers between the two groups (p-value=1.000) Conclusions: No association between P. gingivalis and the development of ACPA, the rise in ESR levels as disease severity escalates underscores the potential practicality of using ESR as an indicator to evaluate disease activity in RA, a trend towards a higher occurrence of gum problems among RA patients especially in category of patients developed gum problems before the onset of RA.

E15 Immunopositive and immunonegative juvenile idiopathic arthritis: what makes the difference?

Abstract Background Juvenile idiopathic arthritis (JIA) is a complex pediatric rheumatic disease of polymorphic expression. The immunological assessment is commonly performed during this disease. Objectives The objective of this work was to evaluate the difference between immunopositive and immunonegative forms of JIA. Methods We conducted a retrospective study including adults with long-standing JIA according to International League of Associations of Rheumatology (ILAR) criteria over a 28-year period (1994 – 2022). We retrieved the immunological results of all patients. The disease was considered immunopositive in case of rheumatoid factor (RF) and/or anti-citrullinated peptide antibody (ACPA) positivity. Results We included 29 patients (12 men and 17 women) with a mean age of 35.69 ± 11.72 [18–61] years. The mean age of disease onset was 11.10 ± 4.25 [2–16] years. The average diagnostic delay was 52.96 ± 95.97 [0–336] months. The average disease duration was 24.48 ± 12.76 [1–47] years. The mean body mass index (BMI) was 21.20 ± 4.88 [14.17–27.55] kg/m2, 8 patients had a normal BMI. Growth delay was noted in 3 cases. The polyarticular form was the most frequent, observed in 55.2% of cases. At least one extra-articular manifestation was noted in 16 patients: ophthalmologic, skin, cardiac, pulmonary, and renal involvement were found in 6,4,4,3 and 2 cases, respectively. Osteoporosis was noted in 7 cases. Mean C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were 42.74 ± 63.37 [2–218] mg/l and 69.67 ± 36.23 [36–108] mm/h. Bone erosions, hip involvement and atlantoaxial dislocation were noted in 18, 14, and 4 cases, respectively. Rheumatoid factor, ACPA and anti-nuclear antibodies were observed in 12, 7 and 5 cases respectively. The disease was considered immunopositive in 13 cases. Our comparative study found that women had more immunopositive forms (84.6% vs 15.4%; P = 0.010). In addition, osteoporosis was less frequent in immunopositive JIA (11.1% vs 88.9%; P = 0.003). Growth delay was only observed in immunopositive JIA (P = 0.012). Furthermore, the age at disease onset was greater in the immunopositive group (12.85 ± 2.94 vs 9.69 ± 4.7 years; P = 0.045). However, no significant differences were identified when comparing the rest of the JIA characteristics. Conclusion Evaluation of the immunological profile is required in JIA. Our study found associations of RF and/or ACPA positivity with age at disease onset, female gender, osteoporosis, and growth delay in JIA.

Brief report: can COVID-19 infection trigger rheumatoid arthritis-associated autoimmunity in individuals at risk for the disease? A nested cohort study.

To investigate the association between severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) infection and subsequent development of autoimmunity or pre-clinical manifestations associated with rheumatoid arthritis (RA) in at risk population. This is a nested study within a prospective cohort of first-degree relatives of RA patients (RA-FDR). Participants are tested for RA-associated autoantibodies (anti-citrullinated peptide antibodies (ACPA)/rheumatoid factor (RF)) and clinical signs and symptoms suggestive of early disease. SARS-CoV-2 infections were self-reported between March 2020 and January 2023. All individuals with a pre-pandemic (sample 1) and a post-pandemic sample (sample 2) were included in the analysis. The exposure of interest was self-reported SARS-CoV-2 infection. The primary outcome was a clinically significant change in RA-associated autoantibody serum titers. Secondary outcomes included: becoming seropositive, becoming symptomatic, developing classifiable RA. Among 168 RA-FDRs, 109 reported a SARS-CoV-2 infection between sample 1 and sample 2. During this period, 2 RA-FDRs (1.2%) became anti-CCP2 seropositive, none became anti-CCP3 IgG positive, 6 (3.6%) became RF IgM seropositive, 1 became (0.6%) RF IgA seropositive, 19 (11.3%) became symptomatic and none developed classifiable RA. SARS-CoV-2 infection was not significantly associated with increases in RA autoantibody titers or with secondary outcomes. We could not detect an association between SARS-CoV-2 infection and subsequent development of RA-associated autoimmunity, nor signs or symptoms of RA in an at risk population. These findings do not support the hypothesis that SARS-CoV-2 infections triggers the immune onset of RA.

Outcomes of undifferentiated peripheral inflammatory arthritis in real-world practice. A longitudinal cohort study.

Undifferentiated peripheral inflammatory arthritis (UPIA) may have 3 different courses, including evolution to differentiated arthritis, remaining undifferentiated, and self-limited course. The purpose of this study was to provide a real-world evidence for predictors of outcomes in UPIA in a longitudinal cohort of patients. Patients enrolled in the CTDRC-UA cohort were screened for eligibility. Inclusion criteria were: (i) having synovitis in ≥ 1 joint, (ii) not meeting the criteria of any other rheumatic disease, (iii) having at least 2 visits per year, iv) included in the cohort during the period of 2004 to 2021, and (v) having active disease at cohort entry. Two hundred and three patients who met the inclusion criteria were followed up until January 2023. Medication-free remissions occurred in 42 (20.7%) cases. In 24 (11.8%) cases, the disease met the criteria of other rheumatic diseases, of which rheumatoid arthritis (RA) was the most common. In addition, joint damage occurred in 33 (16.3%) cases. Predictors of medication-free remissions were absence of comorbidity, starting a sustained remission at≤ 6months, and having no flare. Factors associated with disease evolution to RA were anti-citrullinated peptide antibody (ACPA) positivity, non-adherence to therapy, not going into sustained remission and having flare. Delay in treatment for > 3months and being ACPA positive were the predictors of joint damage. Although the majority of UIPA cases treated with step-up combination therapy with DMARDs do not progress to RA, most require continued treatment and a few achieve medication-free remissions. Key Points • Undifferentiated peripheral inflammatory arthritis (UPIA) can progress to rheumatoid arthritis in 11% of cases; and lack of sustained remission, being anti-citrullinated peptide antibody positive, non-adherence to therapy, and having flare are its predictors. • Medication-free remissions occur in 21% of patients with UPIA; and absence of comorbidity, starting a sustained remissionat ≤ 6months, and having no flare are its predictors. • Initiating treatment in the window of opportunity may lead to a better joint outcome.

The onset of de novo autoantibodies in healthcare workers after mRNA based anti-SARS-CoV-2 vaccines: a single centre prospective follow-up study

Nowadays, data concerning the risk of autoimmune disease after SARS-CoV-2 (COVID-19) vaccination is controversial. The aim of this single centre prospective follow-up study was to evaluate whether healthcare workers (HCWs) vaccinated with BNT162b2 mRNA and mRNA-1273 will show a development and/or a persistence of autoantibodies, focussing on the detection of antibodies against nuclear antigens (antinuclear antibodies, ANA). We enrolled 155 HCWs, however only 108 of them received the third dose and were considered for further analysis. Blood samples were collected before vaccine inoculation (T0), at 3 (T1) and 12 months (T2) after the first dose. All samples were analysed for the presence of a) ANA using indirect Immunofluorescence [IIF] (dilutions of 1:80, 1:160. 1:320 and 1:640), and anti-smooth muscle antibodies (ASMA); b) anti-myeloperoxidase (anti-MPO), anti-proteinase 3 (anti-PR3) and anti-citrullinated peptide antibodies (aCCP) [FEIA]; c) anti-phospholipid antibodies (anticardiolipin [aCL], anti-beta-2- glycoprotein I [anti-ß-2GPI] (Chemiluminescence). Line-blot technology was performed using the following kit: EUROLINE ANA profile 3 plus DFS70 (IgG). Our research suggests that mRNA based anti-SARSCoV-2 vaccines can induce the production of de novo ANA in 22/77(28,57%) of subjects and that the percentage of positivity seems to be directly correlated to the number of vaccine expositions: 6/77 (7,79%) after 2 doses; 16/77 (20,78%) after 3 doses. Since it is known that hyperstimulation of the immune system could lead to autoimmunity, these preliminary results seem to further sustain the idea that the hyperstimulation of the immune system might lead to an autoinflammatory mechanism and eventually to autoimmune disorders. However, the link between SARS-CoV-2 vaccination and the development of autoimmune diseases needs to be further investigated.

The Sizes and Composition of HDL-Cholesterol Are Significantly Associated with Inflammation in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA), a chronic inflammatory disease, carries a significant burden of atherosclerotic cardiovascular diseases (ASCVD). With their heterogeneous composition, high-density lipoprotein (HDL) particles have varied athero-protective properties, and some may even increase ASCVD risk. In this prospective and cross-sectional study, we aimed to examine the relationship between HDL sizes/metabolites and inflammation in RA. Using 1H-NMR-based lipid/metabolomics, differential HDL-related metabolites were identified between RA patients and healthy control (HC) subjects and between RA patients with and without anti-citrullinated peptide antibodies (ACPA). The correlation between the discriminative HDL-related metabolites and C-reactive protein (CRP) was evaluated in RA patients. RA patients demonstrated higher particle number, lipids, cholesterol, cholesterol ester, free cholesterol, and phospholipids in large/very large-sized HDLs. ACPA-positive patients had higher L-HDL-C and L-HDL-CE but lower small-/medium-sized HDL-TG levels than ACPA-negative patients. An inverse correlation was found between CRP levels and small-sized HDLs. Janus kinase inhibitor treatment was associated with increased serum small-sized HDL-related metabolites and decreased CRP levels. We are the first to reveal the significant associations between RA inflammation and HDL sizes/metabolites. A potential link between ACPA positivity and changes in serum levels of HDL-related metabolites was also observed in RA patients.