Anti-cyclic Citrullinated Peptide Research Articles

The characteristics and associated factors of hand dysfunction in patients with rheumatoid arthritis

Objective: To investigate the characteristics of hand dysfunction and its associated factors in patients with rheumatoid arthritis (RA). Methods: A cross-sectional study. Patients with RA were recruited from January 2019 to April 2024 at the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. Demographic and clinical data were collected, including age, gender, active smoking, disease duration, time of morning stiffness, rheumatoid factor and anti-cyclic citrullinated peptide antibody, disease activity, radiographic indicators, and hand function assessment. Hand function was assessed by grip strength measures and self-reported items related to hand function in the Stanford Health Assessment Questionnaire. Factors related to hand function were analyzed by logistic regression analyses. Results: A total of 1 079 RA patients were recruited [mean age: (53.0±12.6) years]. Overall, 72.6% (783/1 079) patients experienced a decrease in grip strength, 57.2% (617/1 079) patients experienced a decreased grip strength in both hands, with the average grip strength of the left and right hands decreasing by 16.3% and 14.1%, respectively, compared to normal values; 39.9% (430/1 079) patients had self-reported hand dysfunction. There were 185 (17.1%) older RA patients (age ≥65 years). The proportion of older RA patients with decreased grip strength [89.7% (166/185) vs. 69.0% (617/894)] and degree of decrease in grip strength compared to normal values (left hand:-35.3%±30.6% vs. -12.3%±38.6%; right hand:-32.6%±32.3% vs. -10.3%±42.1%) were significantly higher than that in young patients, and the proportion of older patients with self-reported hand dysfunction was also significantly higher [53.0% (98/185) vs. 37.1% (332/894), all P<0.001]. Multivariate logistic regression analysis showed that pain visual analogue scale (OR=1.375, 95%CI 1.020-1.854) was independently associated with grip strength decrease in older RA patients, while the 28-joint tender joint count (OR=1.151, 95%CI 1.063-1.246) and provider global assessment of disease activity (OR=1.381, 95%CI 1.171-1.628) were associated with self-reported hand dysfunction. Conclusions: Hand dysfunction is common in RA patients, especially among older RA patients, which is related to pain, joint tenderness and provider global assessment of disease activity. This result implies the importance of pain management in RA patients.

Endogenous Retroelement Activation is Implicated in Interferon-α Production and Anti-Cyclic Citrullinated Peptide Autoantibody Generation in Early Rheumatoid Arthritis.

Endogenous retroelements (EREs) stimulate type 1 interferon (IFN-I) production but have not been explored as potential interferonogenic triggers in rheumatoid arthritis (RA). We investigated ERE expression in early RA (eRA), a period in which IFN-I levels are increased. ERE expression (long terminal repeat [LTR] 5, long interspersed nuclear element 1 [LINE-1], and short interspersed nuclear element [SINE]) in disease-modifying treatment-naïve eRA whole-blood and bulk synovial tissue samples was examined by reverse transcription-polymerase chain reaction and NanoString alongside IFN-α activity. Circulating lymphocyte subsets, including B cell subsets, from patients with eRA and early psoriatic arthritis (ePsA) were flow cytometrically sorted and similarly examined. Existing established RA and osteoarthritis (OA) synovial single-cell sequencing data were reinterrogated to identify repeat elements, and associations were explored. There was significant coexpression of all ERE classes and IFNA in eRA synovial tissue samples (n = 22, P < 0.0001) and significant positive associations between whole-blood LINE-1 expression (n = 56) and circulating IFN-α protein (P = 0.018) and anti-cyclic citrullinated peptide (anti-CCP) titers (P < 0.0001). ERE expression was highest in circulating eRA B cells, particularly naïve B cells compared with ePsA, with possible ERE regulation by SAM and HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1 transcription (SAMDH1) implicated and associations with IFNA again observed. Finally, in established RA synovium, LTRs, particularly human endogenous retroviral sequence K (HERVK), were most increased in RA compared with OA, in which, for all synovial subsets (monocytes, B cells, T cells, and fibroblasts), ERE expression associated with increased IFN-I signaling (P < 0.001). Peripheral blood and synovial ERE expression is examined for the first time in eRA, highlighting both a potential causal relationship between ERE and IFN-I production and an intriguing association with anti-CCP autoantibodies. This suggests EREs may contribute to RA pathophysiology with implications for future novel therapeutic strategies.

Impact of Likelihood Ratios of Rheumatoid Factor and Anti-Cyclic Citrullinated Peptide Antibody in Clinical Diagnosis of Rheumatoid Arthritis by Two Available Platforms.

Background/Objectives: Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases, characterized by an articular and extra-articular involvement, where autoantibodies, such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPAs), are important biomarkers for the diagnosis. Autoantibody determination can be carried out using different assays. However, the results obtained are usually expressed in arbitrary units that are not comparable. Therefore, the aim of this study is to improve clinical interpretation of RF and ACPA test results using the likelihood ratio (LR). Methods: RF and ACPA titers were analyzed by turbidimetry and chemiluminescence using Optilite and BIO-FLASH systems, respectively, in 781 samples from patients with RA and in 1970 controls. Results: The higher the antibody titer of RF or ACPA, the higher the LR for RA. The definition of test result interval-specific LR based on predefined specificities for antibody levels provides more information than the use of the cut-off set by the manufacturer for each antibody. Conclusions: The LR for RA increased with an increasing antibody level. In addition, the use of test result interval-specific LR allows better clinical interpretation for RF and ACPA assays compared to the traditional idea of interpreting antibody results in a dichotomous manner, such as negative or positive.

Coexisting rheumatoid arthritis and sickle cell disease: case series and literature review.

Rheumatoid arthritis (RA) is rarely reported among patients with sickle cell disease (SCD). RA treatment in these patients is believed to be more challenging due to fear of increasing the risk of infection and complications of SCD. We are reporting 7 patients with concurrent SCD and RA. The average age at the time of the diagnosis of RA was 33.3±12.6 years (ranging from 16 to 53 years), and most were women (5/7). Most of the patients were positive for rheumatoid factor (6/7) or anticyclic citrullinated peptide (6/7). Four patients were treated with hydroxyurea. The most used antirheumatic drugs were methotrexate (7/7), biologic agents (5/7), and prednisone (4/7). Two patients were in remission, four had low and one had high disease activity. Four patients (4/7) had avascular necrosis, two in the shoulders and two in the hip joints. Four patients had emergency visits or hospitalizations within one year of the diagnosis of RA, but none had blood transfusions, infections, or death. The start of antirheumatic medication was not associated with an increased risk of infection, blood transfusions, emergency visits, or hospitalizations, nor with a worsening of laboratory measures. The findings suggest that the treatment of RA in patients with SCD should follow the same strategy as in patients without SCD. However, treatment should be individualized according to the individual patient's risk of infection and SCD complications.

Differences and Similarities Between Children and Adults With Rhupus Syndrome.

In this study, we aimed to evaluate and compare the characteristics of pediatric and adult rhupus patients. Thirty pediatric patients with rhupus syndrome and 15 adult patients with rhupus syndrome were included in this study. Similarities and differences between both groups were evaluated. The time elapsed between the diagnosis of juvenile idiopathic arthritis (JIA)/rheumatoid arthritis (RA) and the diagnosis of systemic lupus erythematosus (SLE) was longer in adults than in pediatric patients (p < 0.001). While the most common phenotypes at disease onset were JIA/RA in both adults and children, SLE was more prevalent in pediatric patients and RA in adult patients at the last visit (both p < 0.001). Cutaneous findings, oral ulcers, hematological and renal involvement, hypocomplementemia, and antidouble-stranded DNA positivity were more frequent in pediatric patients, whereas constitutional findings, nonscarring alopecia, neuropsychiatric involvement, and anticyclic citrullinated peptide positivity were more common in adults (all p < 0.001). Asymmetric polyarthritis was more prevalent in pediatric patients, whereas symmetric polyarthritis was more common in adult patients (both p < 0.001). Erosive arthritis was more frequently observed in adult patients (p < 0.001). In the treatment, mycophenolate mofetil was more commonly prescribed to pediatric patients, while rituximab was more frequently used for adult patients in the treatment of SLE compared to pediatric patients (both p < 0.001). Additionally, leflunomide was more commonly used in JIA/RA treatment in adult patients compared to pediatric patients (p < 0.001). This is the first study comparing pediatric and adult patients with rhupus syndrome. Revealing these differences and similarities will contribute significantly to the literature.

Aire attenuate collagen-induced arthritis by suppressing T follicular helper cells through ICOSL

ObjectiveTo assess the expression levels of autoimmune regulator (Aire) and inducible costimulator molecule ligand (ICOSL), as well as T follicular helper (Tfh) cell numbers in rheumatoid arthritis (RA) patients, and to explore their relationship with RA severity. We also aimed to investigate the effect of Aire on arthritis and its underlying mechanisms. MethodsThe expression levels of Aire, ICOSL, and Tfh cell numbers were measured in RA patients. The relationship between these factors and the levels of anticyclic citrullinated peptide antibodies (Anti-CCP) as well as the Disease Activity Score in 28 joints (DAS28) was analyzed. To investigate the effect of Aire on arthritis, Aire-overexpressing bone marrow-derived dendritic cells (Aire-BMDCs) and recombinant ICOSL were transferred into collagen-induced arthritis (CIA) mice, the symptoms, clinical scores, anti-collagen type II antibodies (anti-CII Abs), rheumatoid factor (RF), proportions of Tfh cells, and percentages of germinal center (GC) B cells in CIA mice were examined. ResultsThe results showed that Aire levels were significantly decreased in CD14+ PBMCs from patients with RA, and there were negative correlations between ICOSL expression levels, Tfh cell numbers, and Aire expression. Additionally, these factors were correlated with Anti-CCP levels and DAS28. Aire-BMDCs could influence Tfh differentiation, GC B cell development, as well as the levels of anti-CII Abs and RF, which further alleviate the symptoms and reduce clinical scores partly through ICOSL in CIA mice. ConclusionsThe findings suggest that Aire may alleviate rheumatoid arthritis by inhibiting ICOSL, which further inhibits Tfh cell differentiation and autoantibody production.

Efficacy and safety of baricitinib in rheumatoid arthritis patients with moderate renal impairment: a multicenter propensity score matching study

BackgroundThis study aimed to compare the efficacy and safety of baricitinib in patients with rheumatoid arthritis (RA) receiving different doses based on renal function.MethodsWe conducted a retrospective study within the JAK Study Group, involving 23 facilities in Fukuoka Prefecture, examining patients treated with baricitinib for RA. Patients were categorized into two dose groups: 4 mg with normal/mild renal dysfunction and 2 mg with moderate renal dysfunction. Baricitinib’s efficacy, retention rate, and safety were compared between the groups after propensity score matching.ResultsAfter propensity score matching, disease duration, methotrexate dosage, and anti-cyclic citrullinated peptide antibody positivity rate were balanced across 33 patients in both groups. No significant differences were observed between the groups in tender/swollen joint counts, changes in evaluator/patient global assessments, achievement rate of low disease activity, remission rate on clinical/simplified disease activity indices, or retention rate. Additionally, the incidence of adverse events aligned with previous reports, indicating similar drug safety profiles.ConclusionsBaricitinib 2 mg in RA patients with moderate renal dysfunction showed comparable efficacy and retention rate to 4 mg in patients with normal/mild renal dysfunction. The incidence and types of adverse events were consistent with previous studies, indicating the safety of the drug at these dosages.

Unmet Needs and Current Challenges of Rheumatoid Arthritis: Difficult-to-Treat Rheumatoid Arthritis and Late-Onset Rheumatoid Arthritis.

Despite remarkable advances in the management of RA, there are still unmet needs that rheumatologists need to address. In this review, we focused on difficult-to-treat RA (D2T RA) and late-onset RA (LORA), and summarized their characteristics and management. The prevalence of D2T RA is reported to be 6-28% and many factors have been identified as risk factors for D2T RA, including female sex, long disease duration, seropositivity for rheumatoid factor and anti-cyclic citrullinated peptide antibody and their high titer, baseline high disease activity, and comorbidities. D2T RA is broadly divided into inflammatory and non-inflammatory conditions, and clinical features differ according to background. A proportion of D2T RA can be managed with treatment modification, mainly with interleukin-6 receptor inhibitors or Janus kinase inhibitors, but some D2T RA patients have a poor prognosis; thus, the implementation of precision medicine by stratifying patients according to disease status is needed. In the aging society, the epidemiology of RA is changing and the prevalence of LORA is increasing worldwide. LORA has distinct clinical features compared with young-onset RA, such as acute onset, low seropositivity, and high inflammation. The pathogenesis of LORA remains to be elucidated, but proinflammatory cytokines, including interleukin-6, have been reported to be significantly elevated. LORA has several management concerns other than RA itself, such as geriatric syndrome and multimorbidity. The treat-to-target strategy is effective for LORA, but the evidence is still lacking; thus, it is important to accumulate clinical and related basic data to establish the optimal treatment strategy for LORA.

Cystatin D serum level in rheumatoid arthritis and its relation to disease activity

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune condition that causes synovitis and functional impairment. Currently, the most often utilized biomarkers for monitoring disease activity and severity are acute phase proteins, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP).However, discrepancies have been found between the clinical inflammation and their levels. Therefore, there is a strong need for a novel biomarker to forecast how RA will proceed clinically and monitor the response to therapy. This study assessed the diagnostic value of serum cystatin D in RA patients and its potential as a biomarker for disease activity monitoring.ResultsRA patients had considerably greater serum levels of cystatin D than the control group. These values showed a positive correlation with Disease Activity Score-28 (DAS28), ESR, CRP, grayscale synovitis, power Doppler synovitis, grayscale tenosynovitis (p < 0.001), and erosions, sum scores (p < 0.05). Nonetheless, no noteworthy association was observed between the serum cystatin D levels and sociodemographic data, rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP).ConclusionCystatin D serum levels are higher in RA patients compared to healthy subjects and are strongly correlated with the activity of RA. It can be a valuable biomarker for evaluating RA disease activity.

Prediction model for bone erosion in rheumatoid arthritis based on musculoskeletal ultrasound and clinical risk factors.

Progressive bone erosion (BE) is a prominent manifestation of structural damage in rheumatoid arthritis (RA). This study aimed to construct and validate a BE prediction model (BEPM) for RA based on musculoskeletal ultrasound and clinical risk factors. A total of 312 RA patients without BE were consecutively collected and followed up for 2years, who were divided into BE group and non-bone erosion group, as confirmed by two radiology experts based on at least two imaging techniques. Relevant clinical information, such as anti-cyclic citrullinated peptide (ACCP) antibody and disease duration, was collected. Musculoskeletal ultrasound examinations were performed on all patients upon admission. Univariate and binary logistic regression analyses were conducted to identify risk factors for BE and to establish the prediction model. The calibration, diagnostic efficacy, and clinical effectiveness of BEPM were evaluated by calibration curve plots, receiver-operating characteristic curve, and decision curve analysis (DCA). Binary logistic regression analysis screened four variables, including synovial hyperplasia, synovial blood flow, ACCP + , and disease duration, into the prediction model. BEPM exhibited good diagnostic performance in both the training and validation groups, with area under the curve values of 0.949 (95% CI 0.924-0.973) and 0.965 (95% CI 0.935-0.996), respectively. Using 0.376 as the optical cutoff value for BE, the sensitivity, specificity, and Youden index of the model in the training group were 86.0%, 90.4%, and 76.4%, respectively. In the DCA curves, BEPM indicated overall good population benefit. BEPM demonstrates high diagnostic performance and clinical utility, and may be a useful clinical model for predicting BE in patients with RA. Key Points • Synovial hyperplasia, synovial blood flow, ACCP+ , and disease duration are independent risk factors for bone erosion in RA patients. • BEPM exhibits good diagnostic performance in both the training and validation groups. • Combining musculoskeletal ultrasound parameters with key clinical risk factors to construct a bone erosion model is feasible.

Escalation to Biologics After Methotrexate Among US Veterans With Rheumatoid Arthritis Grouped by Rural Versus Urban Areas.

Racial and ethnic disparities in rheumatoid arthritis (RA) outcomes are well recognized. However, whether disparities in RA treatment selection and outcomes differ by urban versus rural residence, independent of race, have not been studied. Our objective was to evaluate whether biologic disease-modifying antirheumatic drug (bDMARD) initiation after methotrexate administration differs by rural versus urban residence among veterans with RA. In this retrospective cohort study using national US Veterans Affairs (VA) databases, we identified adult patients with RA based on the presence of diagnostic codes and DMARD administration. We included patients receiving an initial prescription of methotrexate (index date) between 2005 and 2014, with data through 2016 used for follow-up. Urban-rural status was categorized using the Veteran Health Administration's Urban/Rural classification. Our primary outcome of interest was time to biologic initiation within two years of starting methotrexate. Multivariable Cox proportional hazards models were conducted adjusting for demographics, comorbidities, and rheumatoid factor or anti-cyclic citrullinated peptide positivity. Among 17,395 veterans with RA (88% male, 42% with rural residence) fulfilling eligibility criteria, 3,259 (19%) initiated a biologic within the first two years of follow-up. In multivariable models, residence in an urban area was associated with a statistically significant higher biologic administration compared to rural areas (adjusted hazard ratio 1.10 [95% confidence interval 1.02-1.18]). Our study found only modest differences in the initiation of biologic therapies among rural- versus urban-residing veterans with RA in the VA health care system. These findings suggest that disparities are not easily explained by rurality within the VA health care system.

Genomic and Serological Rheumatoid Arthritis Biomarkers, MUC5B Promoter Variant, and Interstitial Lung Abnormalities.

Rheumatoid arthritis (RA) has been implicated in interstitial lung disease (ILD) as majority of studies have been comprised of patients with known RA. However, it remains unclear whether an underlying risk for RA in combination with genetic risk for pulmonary fibrosis is associated with radiological markers of early lung injury and fibrosis in broader population samples. Determine whether genetic and serological biomarkers of RA risk in combination with the MUC5B (rs35705950) risk allele (T) are associated with interstitial lung abnormalities (ILA) on computed tomography (CT) scans. Associations of RA-risk HLA-DRB1 alleles (*04:01, *04:08, *04:05, *04:04, *10:01) and serum RA autoantibodies with ILA in the Multi-Ethnic Study of Atherosclerosis (MESA, n=4,018) and COPDGene (n=5,963) cohorts were modeled using logistic regression and adjusted for age, sex, self-reported race and ethnicity, smoking history, body mass index, and principal components of genetic ancestry. The prevalence of an RA risk HLA-DRB1 allele was 16.5% and 21.9% in MESA and COPDGene, respectively. ILA was present in 3.9% and 11% in MESA and COPDGene, respectively. An RA risk HLA-DRB1 allele was not significantly associated with ILA in MESA and COPDGene. In MESA, higher serum levels of IgA rheumatoid factor (RF) and anti-cyclic citrullinated peptide were associated with an odds ratio (OR) for ILA of 1.20 (95% CI 1.07-1.35) and 1.19 (95% CI 1.04-1.37), respectively. Among smokers without baseline ILA, per doubling of IgM RF was associated with an OR for ILA 10 years later of 1.25 (95% CI 1.08-1.43). Associations were not significantly different by MUC5B risk allele status. RA-related HLA-DRB1 alleles were not associated with ILA, whereas higher serum levels of IgM RF among smokers without baseline ILA were associated with subsequent ILA.

Obesity might not alter tofacitinib drug survival in rheumatoid arthritis patients.

Obese rheumatoid arthritis (RA) patients often show reduced responses to traditional treatments, including TNF inhibitors (TNFi). Considering the different mechanisms of action it is important to evaluate the efficacy of tofacitinib in obese patients. This study aims to explore the impact of obesity on the drug survival of tofacitinib in RA patients. This retrospective cohort study included RA patients treated with tofacitinib. Patients were categorized into obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2) groups. The primary outcome was drug survival, assessed using Kaplan-Meier and logistic regression analyses. The study comprised 80RA patients, with 31 (39%) classified as obese. At the 12-month mark, the drug survival rate for tofacitinib was higher in the obese group (81%) compared to the non-obese group (59%). Contrary to univariable analysis, multivariate analysis did not identify obesity as asignificant predictor of drug survival. Other variables including sex, hypertension, diabetes mellitus, and anti-cyclic citrullinated peptide (anti-CCP) positivity also showed no significant association with tofacitinib drug survival. The findings indicate that obesity does not alter the drug survival rate for tofacitinib among RA patients. Univariate analysis reported apotentially higher drug survival rate in obese patients; however, the lack of statistical significance in multivariate analysis and the study's retrospective nature necessitate further research to validate these observations and guide personalized therapeutic strategies for this population.

Prevalence of Subclinical Peripheral Neuropathy in Patients With Autoimmune Connective Tissue Disorders: An Observational Cross-Sectional Study.

Background Autoimmune connective tissue disorders (AICTDs) are a group of chronic inflammatory diseases characterized by immune responses targeting the body's own tissues. Peripheral neuropathy, which can be symmetrical or asymmetrical, is a common complication in AICTD patients. Early detection of subclinical peripheral neuropathy remains challenging, as nerve conduction studies are not routinely performed. This study aimed to determine the prevalence of subclinical peripheral neuropathy among patients with AICTD and to assess its association with potential predictor variables, including laboratory parameters and autoimmune markers. Materials and methods This observational cross-sectional study included 100 patients undergoing treatment for AICTDs for over three years, conducted over 15 months. Ethical approval and informed consent were obtained before detecting subclinical peripheral neuropathy through nerve conduction studies on bilateral ulnar, radial, sural, peroneal, and tibial nerves at a tertiary-level medical college hospital. Inclusion criteria encompassed patients treated at the tertiary hospital, not on immunosuppressants other than steroids, with at least three years of treatment, while exclusions were made for established peripheral neuropathy and other specified conditions. Descriptive statistics, Chi-square/Fisher's exact tests, independent samples t-tests, and logistic regression were used for data analysis at a 0.05 significance level, with IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, NY, USA). Results Subclinical peripheral neuropathy was present in 18% (n = 18) of the study participants, while 82% (n = 82) did not exhibit neuropathy. Patients with subclinical neuropathy had a significantly higher mean age (49.66 ± 4.77 years) compared to those without neuropathy (46.02 ± 12.7 years, p = 0.047). The majority of the study population was female, 79 (79%), and there was no significant gender difference between the groups (p = 0.513). There was no significant association between inflammatory markers (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) and neuropathy. However, patients with subclinical neuropathy were more likely to test positive for rheumatoid factor (RF) (8 (66.7%) vs. 71 (58.5%), p = 0.011) and anti-cyclic citrullinated peptide (Anti-CCP) antibodies (11 (78.5%) vs. 32 (47%), p = 0.032). Steroid use did not significantly affect the presence of neuropathy (p = 0.769). Conclusion The study found a high prevalence of subclinical peripheral neuropathy in AICTD patients, detectable only by nerve conduction studies. RF and Anti-CCP antibodies were associated with subclinical neuropathy, suggesting these markers could guide early detection, and inform treatment intensification to reduce neuropathy prevalence among AICTD patients.

The Impact of Autoantibodies on Outcomes in Patients with Idiopathic Pulmonary Fibrosis: Post-Hoc Analyses of the Phase III ASCEND Trial.

Clinical practice guidelines recommend autoimmune serological testing in patients newly diagnosed with interstitial lung disease of apparently unknown cause who may have idiopathic pulmonary fibrosis (IPF), in order to exclude connective tissue disease (CTD). Autoantibody positivity has been associated with unique patient profiles and prognosis in patients with IPF who otherwise lack a CTD diagnosis. This post-hoc analysis of patients with IPF from the Phase III ASCEND trial (NCT01366209) evaluated the association of antinuclear antibodies (ANA), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) status with baseline disease characteristics, disease progression [percent predicted forced vital capacity (%FVC), forced vital capacity (FVC) volume and progression-free survival (PFS)], and treatment outcomes with pirfenidone and placebo (%FVC, FVC and PFS). Of 555 participants, 244/514 (47.5%) were ANA positive (ANA+), 83/514 (16.1%) had high ANA+ (ANA titre≥1:160 or positive nucleolar- or centromere-staining patterns), 60/555 (10.8%) were RF positive (RF+) and/or anti-CCP positive (anti-CCP+) and 270/514 (52.5%) were autoantibody negative (AAb-). Baseline demographics and characteristics were generally comparable between autoantibody subgroups. Although not statistically significant, more placebo-treated participants with ANA+ or high ANA+ had a decline from baseline to Week 52 of≥10% in %FVC or death (48.7% and 55.9%, respectively) or in FVC volume or death (48.7% and 47.1%, respectively) compared with the AAb- group (%FVC or death: 42.0%; FVC volume or death: 42.0%). The RF+ and/or anti-CCP+ group was similar to AAb-. No differences were observed in PFS. A treatment benefit for pirfenidone versus placebo was observed regardless of autoantibody status [PFS: ANA+ HR (95% CI): 0.56 (0.37 to 0.86), P=0.007; AAb- HR (95% CI): 0.50 (0.32 to 0.78), P=0.002]. IPF disease course did not differ by autoantibody status in ASCEND. Pirfenidone had a treatment benefit regardless of the presence of ANA. ClinicalTrials.gov identifier, NCT01366209.

Immunological markers of rheumatoid arthritis in the Moroccan population

Aim: few studies exist on HLA-DRB1 alleles and their association with RA in North Africa. We aimed to provide an evaluation of the distribution of the HLA-DRB1* and -DQB1* genes in Moroccan patients with early RA. Additionally, we sought to analyze the relationship between HLA molecules and the production of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) in these patients. Methods: 65 patients with rheumatoid arthritis benefited from HLA class II typing (DRB1* and DQB1*) and testing for anti-CCP and RF antibodies. The frequency of HLA alleles was compared to that of 180 healthy controls. Logistic regression analysis was used to investigate the association of HLA-DR and -DQ molecules in the different subgroups according to anti-CCP and RF status. Results: The frequency of HLA-DRB1*04 and *11 alleles is increased in patients compared to controls (OR = 1.9; 95% CI (1.06-3.30), P=0.029; OR=2, 95% CI (1-3.83, P=0.047, respectively). 56 patients (86.1%) were RF positive, and 67.7% were anti-CCP positive. A significant increase in the frequency of DRB1*04 alleles was also noted in seropositive patients. Conclusion: Our results suggest the predisposition of the HLA-DRB1*04 allele and the seropositive status of patients with RA. This could be useful in predicting the evolution of RA and establishing a diagnosis in some patients at an early stage of disease use.

Diagnostic Value of Interleukin 6, Interleukin 12P70, Serum Amyloid A, and Procalcitonin for Rheumatoid Arthritis and Their Relationship With the Disease Activity

To observe the diagnostic value of four serum inflammatory biomarkers, including interleukin 6 (IL-6), interleukin 12P70 (IL-12P70), serum amyloid A (SAA), and procalcitonin (PCT), in rheumatoid arthritis (RA) and to analyze their relationship with the disease activity. The study included 60 RA patients admitted to the Department of Rheumatology at Anhui Provincial Hospital of Traditional Chinese Medicine between December 2022 and December 2023. Thirty healthy individuals from the hospital's physical examination center served as the control group. Serum levels of IL-6 and IL-12P70 were detected using flow cytometry. SAA levels were determined by immunoturbidimetry, and PCT levels were assessed by chemiluminescence. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and anticyclic citrullinated peptide (ACCP) were detected using an automated biochemical analyzer. The 28-joint disease activity scores (DAS28-ESR) based on ESR were observed. Statistical analysis included t-tests, rank-sum tests, and Kruskal-Wallis H tests to compare the expression differences of the biomarkers among different groups. The diagnostic value of these biomarkers for RA was analyzed by ROC curve analysis. Spearman correlation analysis was performed to assess the relationships between the four inflammatory biomarkers and CRP, ESR, RF, ACCP, and DAS28-ESR. 1) The expression levels of SAA, IL-6, and IL-12P70 in the RA group were significantly higher than those in the control group (P<0.01). 2) ROC curve analysis showed that the area under the curve (AUC) for PCT was 0.611 (95% confidence interval [CI]: 0.488-0.735, P>0.05), for SAA, it was 0.819 (95% CI: 0.733-0.906, P<0.01), for IL-6, it was 0.875 (95% CI: 0.803-0.946, P<0.01), and for IL-12P70, it was 0.832 (95% CI: 0.746-0.917, P<0.01). The combined index of IL-6, IL-12P70, SAA, and PCT had an AUC of 0.973 (95% CI: 0.942-1.000, P<0.01). This indicates that the four inflammatory biomarkers can assist in the diagnosis of rheumatoid arthritis. 3) The expression levels of PCT and SAA varied significantly among the high, moderate, and low activity RA groups (P<0.01). 4) In RA patients, CRP was positively correlated with SAA (rs =0.75, P<0.01), and IL-6 (rs =0.52, P<0.01). ESR was positively correlated with SAA (rs =0.36, P<0.01). DAS28-ESR was positively correlated with PCT (rs =0.34, P=0.01), SAA (rs =0.51, P<0.01) and IL-6 (rs =0.33, P=0.01). The four inflammatory biomarkers (PCT, SAA, IL-6, and IL-12P70) are closely related to rheumatoid arthritis disease activity and can serve as serum indicators to assist in the diagnosis and assessment of RA.

Polyarthritis in Sjögren's Syndrome: Difficulties in Distinguishing Extraglandular Manifestation and Associated Rheumatoid Arthritis.

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

Investigating the Association of Aortic Stiffness and Phase Angle with the Clinical Course of Rheumatoid Arthritis.

Aortic stiffness is an independent predictor of cardiovascular events which is increased in rheumatoid arthritis (RA). It can be measured by carotid-femoral pulse wave velocity (cfPWV). Phase angle (PhA) is lower in patients with cardiovascular disease and may be informative in assessing the clinical course of RA. In this observational and cross-sectional study, all RA patients referred to the Imam Khomeini Hospital rheumatology clinic between September 2022 and March 2023 were included in the study. RA activity was assessed using the DAS28 criteria. In the patients, PhA and cfPWV were measured using Inbody-s10 and PulsePen tonometer instruments. The relationships between PhA, cfPWV, clinical course of RA, and CRP were evaluated using regression analysis. 53 patients were included in the study (83% female, mean age 46.5 years). Significant inverse relationships existed between PhA, CRP, and age (P value = 0.003, 0.0001, R: 0.69, respectively). People with aortic stiffness had a lower mean PhA (P value = 0.05). In patients with RA duration of less than 10 years, the cfPWV percentile and the prevalence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) positive cases were higher than in patients with RA duration >10 years (P values = 0.02, 0.01, respectively). With increasing duration of RA, aortic stiffness and positive serology cases decreased. PhA and cfPWV may be useful in assessing the clinical course of RA to prevent cardiovascular events.

Diabetic cheiroarthropathy in uncontrolled type 2 diabetes with positive anti-nuclear antibodies: a case report from Sudan

Background: Diabetic cheiroarthropathy, also known as limited joint mobility, is one of the long-standing complications of type 2 diabetes mellitus (DM). It affects 8–50% of patients with type 1 diabetes and is also seen in type 2 diabetic patients. Consequently, it can mimic many rheumatological diseases and is often underdiagnosed. The authors present a case of a long-standing poorly controlled diabetes with diabetic cheiroarthropathy and diabetic neuropathy, along with positive ANA in the absence of any correlated autoimmune or rheumatological diseases. Case presentation: A 52-year-old female patient with poorly controlled diabetes (her last HbA1c reading was 9.5%) presented to the Rheumatology clinic with flexion deformities of the fingers. The patient has impaired vibration, two-point discrimination, and pinprick sensation in gloves and stock distribution, indicating peripheral neuropathy, entrapment neuropathy in the forms of bilateral carpal tunnel syndrome, and the diagnosis of diabetic cheiroarthropathy was made. Additionally, she has a positive prayer sign and a tabletop sign. Despite the absence of symptoms and signs of autoimmune disorders, this patient has positive anti-nuclear antibodies global (ANA positive by indirect immuno-fluorescence (IIF) 1\320 nucleolar pattern) with a negative: ANA profile, rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (ACPA). Conclusion: Regular and careful hand examination should be part of clinical assessment for diabetic patients as it could be a very simple and useful screening tool for diabetic cheiroarthropathy. Physicians can use this condition as a mirror for microvascular complications of diabetes. This allows for early detection and appropriate interventions to prevent further progression of diabetes-related complications. It is also essential to consider the presence of positive ANA in diabetic cheiroarthropathy despite the absence of any rheumatological and autoimmune diseases.