anti-CCP Research Articles

Rheumatoid meningitis sine arthritis: An emerging cause of isolated pachymeningitis and leptomeningitis with typical features

Background and purposeRheumatoid meningitis (RM) is a meningeal inflammation rarely occurring during the course of rheumatoid arthritis (RA). Anti-citrullinated protein antibodies (ACPA), which are highly specific biomarkers of RA, may allow RM sine arthritis (RMSA) to be diagnosed as an extra-articular early lesion of RA. MRI typically displays pachymeningitis and/or leptomeningitis predating convexity, and CSF diffusivity is focally restricted. Blood ACPA is a strong clue and intrathecal synthesis of ACPA is characteristic although rarely reported. MethodsWe report two cases of RMSA that were confirmed by meningeal biopsy and intrathecal synthesis. ResultsRMSA abated after steroids alone or associated with rituximab. No arthritis occurred during the follow-up. ConclusionRM can occur in the absence of RA.

Contribution of Musculoskeletal Ultrasound in the Diagnosis of Seronegative Rheumatoid Arthritis.

This is a study to investigate the value of musculoskeletal ultrasound for the early diagnosis of seronegative rheumatoid arthritis (SNRA); and to study the relationship between anti-cyclic citrullinated peptide antibody (anti-CCP) and the occurrence of bone erosion in rheumatoid arthritis (RA) detected by ultrasound. A total of 101 patients with RA or osteoarthritis (OA) admitted to the First Affiliated Hospital of Anhui Medical University from July 2022 to December 2023 were selected and divided into the SNRA group, the SPRA group, and the OA group. The patients' metacarpophalangeal joints, proximal interphalangeal joints, distal interphalangeal joints, and wrist joints of both hands were ultrasonically examined separately, and the extensor tendon, flexor tendon, synovium, joint surface, joint cavity, and bone surface were observed. The differences in the detection of joint effusion, bone erosion, and joint space narrowing were not statistically significant between SNRA group and OA group (P > .05), the differences in the detection of synovitis and tenosynovitis were statistically significant (P < .05). The mean levels of synovial hyperplasia grade and synovial blood flow grade between SNRA group and OA group were significantly different (P < .05). The differences in synovitis, tenosynovitis, joint effusion, and joint space narrowing were not statistically significant between SNRA and SPRA groups (P > .05), and the differences in bone erosion were statistically significant (P < .05). The mean levels of synovial hyperplasia grade and synovial blood flow grade between SNRA group and SPRA group were significantly different (P < .05). Logistic regression analysis showed that anti-CCP antibody was an influential factor for bone erosion in RA patients (P < .05). The ROC curve was plotted, and the optimal cut-off value of anti-CCP antibody was 356.5U/mL, at which time the AUC was 0.716, the sensitivity of diagnosing bone erosion was 0.714, the specificity was 0.694, and the Yoden index was 0.408. In summary, ultrasound is helpful for the early diagnosis of SNRA by evaluating the condition of joints, synovium, and tendon sheath, and when anti-CCP antibodies are positive, ultrasound is more likely to detect bone erosion. Ultrasound examination combined with anti-CCP antibody can further observe the joint lesions.

Onset of Rheumatoid Arthritis with eye manifestations (clinical case report)

Objective. Rheumatoid Arthritis may onset with ocular manifestations. The purpose of our work was presentation of clinical case of the onset of rheumatoid arthritis with an eye lesion.Materials and methods. A clinical case of rheumatoid arthritis with an atypical onset was analyzed. As well, a search and review of relevant literature was performed.Results. Patient with rheumatoid arthritis got bilateral ulcerous keratitis, refractory to conventional treatment and complicated by bilateral corneal perforation with iris prolapse. Due to the atypical clinical course of ophthalmic lesions being insusceptible of medical treatment, the patient was examined further. Laboratory immunological workup revealed positive rheumatoid factor, anti-CCP and anti-MCV antibodies. The typical symmetric presentation of arthritis developed 8 months after the onset of ophthalmic disorders. Baseline therapy of rheumatoid arthritis has demonstrated efficacy both in controlling the joint manifestations and preventing relapse of keratitis.Conclusion. The development of eye syndrome may precede articular manifestation of rheumatoid arthritis. While managing patients with recurrent bilateral keratitis, rheumatologic pathology should be suspected.

Peculiarities of laboratory parameters dynamics during helicobacter pylori eradication in patients with rheumatoid arthritis

Helicobacter pylori (H. pylori) is able to participate in the pathogenesis of a number of autoimmune diseases, actively maintains chronic inflammation and stimulates the systemic immune response. The virulence factor of H. pylori is cytotoxin-associated gene A (CagA) is associated with more severe inflammatory reactions, increased risk of poor clinical outcomes and is able to influence the efficacy of infection eradication in patients with rheumatoid arthritis (RA).Purpose of the study. To evaluate laboratory parameters of H. pylori eradication efficacy in RA patients with chronic infection with the strain encoding cytotoxin-associated gene A.Materials and methods. Forty women with RA and confirmed chronic H. pylori infection were included in the study (mean age 55.5±8.7 years; mean disease duration 13.9±9.1 years; DAS-28–3.96±0.56). CagA-IgG associated H. pylori infection was diagnosed in 22 (group I, CagA+) and not diagnosed in 18 (group II, CagA-) patients. All RA patients underwent a course of H. pylori eradication therapy.Results. The process of H. pylori eradication had the most significant effect on laboratory parameters of CagA-negative RA patients (group II). In this group the levels of rheumatoid factor (p=0,028), C-reactive protein (CRP, p=0.001), interleukin-6 (IL-6, p=0.002), tumor necrosis factor alpha (p=0,023), angiopoietinlike protein type 3 (p=0.026) and antibodies to cyclic citrullinated peptide (ACCP, p=0,016) decreased significantly. In patients from group I (CagA+) most parameters remained practically unchanged (p&gt;0.05), except for CRP (p=0.01) and IL-6 (p=0.011). In the short term, the success of eradication in CagA+ patients was significantly lower than in CagA- patients (p=0.033). Moreover, confirmation of successful eradication of H. pylori within the established period of time was extremely rare (p=0.009) in the combination of CagA+ and high titers of ACCP and antibodies to modified citrullinated vimentin.Conclusions. The effectiveness of H. pylori eradication in RA patients depends on the presence of chronic infection with the strain encoding the cytotoxin-associated gene A and the level of antibodies to citrullinated proteins, which should be taken into account when choosing the therapeutic effect on H. pylori in this group.

A comparison of anti-cyclic citrullinated peptides (CCP3 and CCP3.1) autoantibody tests in rheumatoid arthritis

BackgroundAnti-citrullinated protein antibodies (ACPA) are a specific serological biomarker used in the diagnosis of rheumatoid arthritis (RA). In clinical practice ACPA can be identified using immunoassays targeting synthetic cyclic citrullinated peptides (CCP). The 3rd generation anti-CCP IgG antibody (CCP3) offers improved sensitivity compared to the earlier versions. Recently, CCP3.1, capable of detecting both IgG and IgA antibodies, was introduced to enhance sensitivity, especially in patients with early RA. MethodsWe assessed serum CCP3.1 against CCP3 in 331 subjects undergoing RA panel serology, comprising 136 patients with RA and 195 patients without RA. Sera were tested for anti-CCP IgG (CCP3) and anti-CCP IgG/IgA (CCP3.1) antibodies. Clinical performance of these tests was compared at manufacturer-suggested cutoffs. A separate set of 81 patients with a diagnosis of RA by 2010 criteria and whose samples were obtained from within 1-year of RA diagnosis was similarly assessed to evaluate assay performance in an independent clinical RA cohort. ResultsOverall diagnostic accuracy was similar; CCP3 had an area under the curve (AUC) of 0.88, CCP3.1 had an AUC of 0.89. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for CCP3 were 79 %, 91 %, 86 %, and 86 %, respectively. For CCP3.1, sensitivity was 78 %, specificity 93 %, PPV 89 %, NPV 86 %. Both assays demonstrated excellent agreement; positive percent agreement of 94 % and negative percent agreement of 99 %. ConclusionOur findings indicate comparable diagnostic accuracy between CCP3 and CCP3.1 assays in these clinical cohorts.

Higher levels of markers for early atherosclerosis in anti-citrullinated protein antibodies positive individuals at risk for RA, a cross sectional study

ObjectiveTo identify differences in levels of serum biomarkers associated with atherosclerosis between anti-citrullinated protein antibodies (ACPA) positive groups.MethodsCross-sectional data were used from the Dutch Lifelines Cohort Study combined with data derived from RA risk and early RA studies conducted at the University Medical Center Groningen (UMCG).Serum biomarkers of inflammation, endothelial cell activation, tissue remodeling and adipokine, which were previously associated with atherosclerosis, were measured with Luminex in four ACPA positive groups with different characteristics: without joint complaints, with joint complaints, RA risk and early RA groups.ResultsLevels of C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor Necrosis Factor Receptor 1 (TNFR1) and vascular endothelial growth factor (VEGF) were significantly higher in the RA risk and early RA groups compared to the joint complaints and the no joint complaints groups. The difference remained statistically significant after correcting for renal function, smoking and hypertension in multivariate logistic regression analysis, with focus on ACPA positive with joint complaints group versus RA risk group: CRP OR = 2.67, p = 0.033; IL-6 OR = 3.73, p = 0.019; TNFR1 OR = 1.003, p < 0.001; VGEF OR = 8.59, p = 0.019.ConclusionIndividuals at risk for RA have higher levels of inflammatory markers and VEGF, which suggests that they might also have a risk of higher cardiovascular disease (CVD); however, this does not apply to individuals with ACPA positivity with self-reported joint complaints or without joint complaints only. Therefore, it is important that individuals with RA risk are referred to a rheumatologist to rule in or out arthritis/development of RA and discuss CVD risk.

The impact of periodontitis and periodontal treatment on rheumatoid arthritis outcomes: an exploratory clinical trial.

Studies suggest rheumatoid arthritis (RA) patients could benefit from periodontal treatment. However, published data are inconsistent, and there is a need for better-controlled research. Our study aims to address these limitations. In this exploratory randomised delayed-start study, 22 RA patients with moderate/severe periodontitis were subjected to full-mouth debridement. Periodontal and rheumatological assessments, including measuring anti-cyclic citrullinated peptide 2 (CCP2) IgG levels, were performed at baseline (V1), 2 months (V2) and 6 months (V3) after step 1 and 2 of periodontal therapy. Primary outcome was changes in disease activity score for 28 joints (DAS28) between V2 and V1. Secondary outcomes were changes in other rheumatological or periodontal clinical parameters (V2 or V3-V1). RA disease activity was significantly higher in RA patients with severe periodontitis compared to moderate periodontitis at baseline, with significant positive correlations between several rheumatological and periodontal parameters. After periodontal treatment, RA patients with severe, but not moderate, periodontitis demonstrated significant improvements in DAS28 (ΔV2-V1, p = 0.042; ΔV3-V1, p = 0.001) and significant reduction in anti-CCP2 IgG levels at V3 (p = 0.032). Periodontal treatment is locally effective in patients with RA and impacts RA disease activity and anti-CCP2 antibody levels in patients with severe periodontitis. Hence, our data suggest that periodontal assessment and treatment should be integrated in the management of RA patients within a treat-to-target strategy. www.isrctn.com, ISRCTN 17950307.

Association of circulating micro-RNAs (miR-21-5p and miR-142-3p (and tumor necrosis factor-α with Rheumatoid Arthritis

Micro-RNAs (miRNAs) become a promising biomarker for diagnosis due to their stability and reproducibility and could be help to find a new effective treatment. This study is designed to evaluate the diagnostic utility and clinical significance of circulating micro-RNAs (miR-21-5p and miR-142-3p (and tumor necrosis factor-α (TNF-α) for patient with RA and to assess their correlation with disease activity. This case control study involved sixty patients and 30 apparently healthy subjects as control group. The diagnosis was done depending on the classification criteria of American college of rheumatology-European league against rheumatism (ACR- EULAR). Expression levels of circulating miRNA were determined by two step reversed transcription polymerase chain reactions (RT- PCR). The concentrations of TNF-α, anti-citrullinated protein antibodies(ACPA) and C- reactive protein(CRP) were estimated by Enzyme linked immune-sorbent assay technique (ELISA). The expression level of circulating miRNA- 21- 5p and miRNA - 142- 3p was significantly elevated (P <0.01) in patients group as well as the levels of blood ESR, serum CRP, ACPA, and TNF-α compared to controls. There are significant differences (P < 0.01) in miRNA- 21- 5p levels between different patients groups, while the expression of miR-142-3p show non-significant difference (p>0.05). It is found that miRNA- 21-5p expression levels are significantly correlated with RA activity. Both miR-21-5p and miR-142-3p have significant positive correlation with levels of CRP, ACPA, and TNF-α. The level of TNF-α have significant positive correlation with both of CRP and ACPA also with the DAS-28 and CDAI. In conclusion, circulating miR-21- 5p and miRNA - 142- 3p may be associated to RA pathogenesis due to their positive correlation with inflammatory cytokine TNF-α, CRP and ACPA, therefore these miRNAs might be considered new targets for RA treatment, and alterations in their expression could be used for diagnosis and monitoring the disease activity and treatment response.

Possible Protective Effect of Trimetazidine Alone and in Combination with Methotrexate in Attenuating Joint Inflammation in Freund’s Adjuvants Induced Rheumatoid Arthritis in Rats

Abstract Rheumatoid Arthritis is a complex chronic auto-immune systemic illness. It is primarily characterized by synovial hyperplasia and localized pro-inflammatory cytokine production that causes chronic synovitis and a long-lasting inflammation of the joints and bones. The study's goal was to look into the potential anti-arthritic effects of trimetazidine in a rat model of Freund’s complete adjuvant (FCA)-induced arthritis, which has many clinical and biochemical similarities to rheumatoid arthritis (RA). The underlying antirheumatoid arthritis mechanism, as well as its impact on TLR4/NFKB pathway were investigated to understand and confirm its potential efficacy in RA treatment. Our study was based on 4 groups, control group received saline injections, trimetazidine (7.2 mg/kg/day) treated group, methotrexate (0.75 mg/kg/week) treated group and combination group that received both medications in the same doses for 21 days. The degree of ipsilateral paw swelling, ankle diameter, body weight, tissue expression levels of TLR4(toll like receptor) and NFKB (nuclear factor kappa b) in paw, and serum ACPA (anticitrullinated protein antibodies) were all measured. With a slight but not statistically significant impact on ankle diameter, trimetazidine and methotrexate considerably reduced the arthritic symptoms as indicated by ipsilateral paw volume. It had no discernible impact on body weight. Together with the overall improved synovial hyperplasia and cartilage disarrangements, TLR4 and NFKB expression in synovial tissue were reduced. In a rat model of CFA-induced arthritis, trimetazidine displays a considerable anti- inflammatory impact that is even better than methotrexate and has the potential to be anti-arthritic. Additionally, there is a large additive effect between the two medications.

The prognostic value of IgA anti-citrullinated protein antibodies and rheumatoid factor in an early arthritis population with a treat-to-target approach.

The mucosal origin hypothesis of rheumatoid arthritis has renewed the interest in IgA autoantibodies, but their added value over IgG anti-citrullinated protein antibody (ACPA) and IgM rheumatoid factor (RF) for modern treatment outcomes remains unknown. We aimed to investigate the prognostic value of IgA-ACPA and IgA-RF for treatment outcomes in an early arthritis population. IgA-ACPA/RF isotypes were measured in baseline sera from 480 inflammatory arthritis (IA) patients, who were included in the treatment in the Rotterdam Early Arthritis Cohort trial (tREACH). The tREACH trial was a multicentre, stratified, single-blinded trial with a treat-to-target approach. The prognostic value of IgA-ACPA/RF was determined by evaluating differences in (1) quick-attained (< 6months after diagnosis) and persistent remission rates, (2) DMARD-free remission and (3) biological use between IA patients with and without IgA-ACPA/RF over 3years of follow-up. IgA-ACPA was present in 23% of patients and overlapped with IgG-ACPA positivity in 94%. Similarly, IgA-RF overlapped with IgM-RF in 90% of patients. IgA-ACPA positivity was associated with lower DFR rates and more biological use, but this effect was largely mediated by the presence of IgG-ACPA, since this effect disappeared after stratification for IgG-ACPA(HR 0.6, 95%CI 0.2-1.6 for DFR). No differences were observed in 'quick-attained and persistent remission' rates and for IgA-RF. Their seems to be no additional value of IgA-ACPA and IgA-RF for modern, long-term clinical outcomes. The effects of IgA-ACPA seen in our study are largely mediated by the presence of IgG-ACPA. Based on these results, there is no rationale for measuring these isotypes in daily practice.

Anti-carbamylated Protein Antibodies Positivity in Rheumatoid Arthritis and Its Association With Rheumatoid Factor and Anti-cyclic Citrullinated Protein Antibodies.

Background Rheumatoid arthritis (RA) is a widespread autoimmune disease affecting millions of people worldwide. The current markers include anti-cyclic citrullinated peptide (anti-CCP) antibodiesand rheumatoid factor (RF), which are nonspecific and elevated in variousconditions and do not have a prognostic value. They are also elevated in the later stages of the disease. Anti-carbamylated protein (anti-CarP) antibodies have been reported to be associated with joint damage in RA. Therefore, this study aimed to evaluate the sensitivity and specificity of anti-CarP antibodies in individuals with RA and their relationship with inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Methods This was a cross-sectional case-control study conducted from April 2020 to March 2021 at the Saveetha Medical College, Chennai, India. The age makeup of the three groups was evaluated: Group 1 comprised anti-CCP and RF-positive patients; Group 2 comprised anti-CCP and RF-negative patients; and Group 3 was the control group, which comprised healthy volunteers. Patient samples, including blood and serum, have been utilized to conduct various assessments aimed at evaluating biomarkers such as CRP, ESR, RF, and autoantibodies like anti-CCP and anti-CarP. Results This study examined the role of various autoantibodies and biomarkers in RA across three distinct groups. Group 1 predominantly consisted of middle-aged individuals, and women constituted the majority in both Group 1 and Group 2, consistent with higher RA prevalence among females. In Group 1, 65.7% of patients tested positive for anti-CarP, while in Group 2, 48.6% tested positiveeven when RF and anti-CCP antibodies were absent. This suggests a potential diagnostic role for anti-CarP antibodies in identifying RA patients early. CRP and ESR levels were significantly elevated in RA patients (Groups 1 and 2) compared to healthy controls (Group 3), indicating higher inflammatory activity in affected individuals. We also observed that anti-CarPantibodies had a specificity of 69.1% and a sensitivity of 78.2%. Positive correlations between the diagnosis of RA and anti-CarP antibody positivity were observed across the groups and correlated well with the inflammatory markers and signs such as joint damage. The data were found to be statistically significant. Conclusions Our study showed a significant correlation between joint damage and CRP levels and a positive correlation between anti-CarP antibodies and ESR and CRP values. These findings suggest that anti-CarP antibodies can offer certain advantages over RF and anti-CCP antibodies in RA diagnosis due to their early detection potential, higher specificity, complementary diagnostic role, and predictive value for disease severity.

Prevention of Rheumatoid Arthritis in At-Risk Individuals: Current Status and Future Prospects.

Early intervention has been the cornerstone of improving outcomes in patients with rheumatoid arthritis. Over the past decade, the boundaries have been pushed in an attempt to achieve effective prevention strategies in those who are at high risk of developing rheumatoid arthritis. Core risk factors including the presence of serum anti-citrullinated protein antibodies, arthralgia and subclinical inflammation on imaging are highly predictive of arthritis development. The influence of air pollution, diet and the role of microbiome on disease progression are less clear. In turn, therapeutic focus has shifted to an earlier pre-arthritis phase of the disease continuum where the clinically apparent arthritis may potentially be intercepted. Seven proof-of-concept interventional trials in at-risk individuals have been conducted so far. Whether true prevention of rheumatoid arthritis is possible remains elusive. Promising signals towards permanent disease modulation and improvement in symptom burden were seen with some immunomodulatory therapies, whilst others were unsuccessful. Long-term follow-up is required to ascertain a true effect. Looking forward, a better understanding of the natural history and underlying biological mechanisms of arthritis development and more accurate, validated risk stratification is needed.

Immunophenotypic Landscape of synovial tissue in rheumatoid arthritis: Insights from ACPA status

ObjectiveTo examine the clinical features and synovial pathologies in rheumatoid arthritis (RA) patients across varying titers of circulating anti-citrullinated protein antibodies (ACPA). MethodologyWe devised a negative pressure suction and rebound synovial biopsy tool to enhance the yield of synovial biopsies, noted for its ease and safety of use. This research involved a retrospective examination of 60 active RA patients who underwent synovial biopsies with this tool from June to November 2023 at our institution. A range of disease activity markers were collected, including DAS28-CRP, ESR, CRP, count of swollen and tender joints, VAS pain scale, and so forth. Synovial tissue underwent HE staining and immunohistochemistry, including synovitis grading (GSS) and counting of B cells (CD20), T cells (CD3), macrophages (CD68), and plasma cells (CD138). Participantswere categorized into three groups as per ACPA titers: ACPA-negative (0–5U/mL), low-titer (5–20U/mL), and high-titer (above 20U/mL). The study compared the clinical features and synovial pathologies across these groups. ResultsOf the 60 RA patients, they were segregated into three groups based on ACPA titers: 20 in ACPA-negative, 9 in the low-titer group, and 31 in the high-titer group. No significant differences were observed in GSS scores, synovial cell proliferation and loss, matrix activation, inflammatory infiltration, and neovascularization among these groups (P > 0.05). The high-titer ACPA group demonstrated significantly increased counts of CD3+ T cells, CD20+ B cells, and CD68+ macrophages in synovial tissues compared to the ACPA-negative and low-titer groups (p < 0.05), along with a higher incidence of ectopic lymphoid neogenesis (p < 0.05). Ordinal logistic regression revealed that rheumatoid factor (RF), and counts of synovial T cells, B cells, macrophages, and ectopic lymphoid neogenesis correlated with ACPA titers (P < 0.05), particularly lymphoid neogenesis (OR = 3.63, P = 0.023). ConclusionRA patients with high-titer ACPA demonstrate elevated levels of inflammatory cell infiltration in synovial tissues, with ectopic lymphoid neogenesis showing a strong correlation with high ACPA positivity.

The Impact of Rheumatoid Arthritis on First Nations and How We Can Work With Communities to Prevent It.

Rheumatoid arthritis (RA) is prevalent in many Indigenous North American First Nations (FN) and tends to be seropositive, familial, and disabling, as well as associated with highly unfavorable outcomes such as early mortality. The risk of developing RA is based on a perfect storm of gene-environment interactions underpinning this risk. The gene-environment interactions include a high frequency of shared epitope encoding HLA alleles, particularly HLA-DRB1*1402, in the background population, and prevalent predisposing environmental factors such as smoking and periodontal disease. Together, these provide a compelling rationale for an RA prevention agenda in FN communities. Our research team has worked in partnership with several FN communities to prospectively follow the first-degree relatives of FN patients with RA, with the aim of better understanding the preclinical stages of RA in this population. We have focused on specific features of the anticitrullinated protein antibodies (ACPA) and other proteomic biomarkers as predictors of future development of RA. These studies have now led us to consider interventions having a favorable risk-benefit ratio if applied at a stage prior to a hypothetical "point of no return," when the autoimmunity potentially becomes irreversible. Based on a supportive mouse model and available human studies of curcumin, omega-3, and vitamin D supplements, we are undertaking studies where we screen communities using dried blood spot technology adapted for the detection of ACPA, and then enrolling ACPA-positive individuals in studies that use a combination of these supplements. These studies are guided by shared decision-making principles.

Estimation of Some Pro- and Anti-Inflammatory Interleukins in Rheumatoid Arthritis of Iraqi Patients

Abstract Background: Rheumatoid arthritis (RA) is an inflammatory condition that mostly affects synovial joints. It produces severe swelling and ongoing inflammation, and as it worsens, the cartilage and bone begin to erode, resulting in deformed joints and bone erosion. Objectives: The purpose of this study is to evaluate the levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies and determine the role of interleukin-1 beta (IL-1β), interleukin-18 (IL-18), interleukin-38 (IL-38), and transforming growth factor-beta2 (TGF-β2) in studied groups (RA patients and apparently healthy control). Materials and Methods: The study included collecting blood samples from a group of patients infected with RA involving 60 patients (21 male and 39 female), and the healthy group included 50 individuals as control group (21 males and 29 females). Results: The outcomes showed of anti-CCP a highly significant difference for RA patients compared to the control group by 0.603 ± 0.02 and 0.274 ± 0.01, respectively, and some immunological parameters that involve inflammation-promoting interleukins (IL-1β and IL-18), the results showed the significant differences at the level (P &lt; 0.01) of patients was 126.79 ± 4.18 and 194.37 ± 12.71 compared with control 91.85 ± 2.11 and 92.27 ± 2.08, respectively. The identical results to measure anti-inflammatory interleukins (IL-38, TGF-β2) represented of patients were 190.43 ± 9.82 and 403.23 ± 21.20 compared with control group was 88.39 ± 1.56 and 115.59 ± 5.63, respectively. Conclusion: The immunological parameters represented high expression of pro-inflammatory interleukins (IL-1β and IL-18), so, elevation levels of anti-inflammatory interleukins (IL-38 and TGF-β2) of RA patients.

Thyroid dysfunction and autoantibodies in rheumatoid arthritis patients at King Saud Medical City: A retrospective cohort study

Abstract: BACKGROUND: Autoimmune thyroid diseases often coexist with conditions such as Sjögren’s syndrome and rheumatoid arthritis (RA). Studies have shown that patients with RA are at an increased risk of thyroid dysfunction. Studies conducted in Egypt and Jeddah have demonstrated a higher prevalence of thyroid dysfunction in patients with RA. This study aimed to determine the prevalence of thyroid dysfunction and its characteristics in patients with RA treated at a single center in Saudi Arabia. METHODS: This was a retrospective cohort study conducted at King Saud Medical City, Riyadh, Saudi Arabia. All patients with RA who qualified for the American Rheumatism Association criteria between 2016 and 2021 were eligible for inclusion. All patients underwent clinical examination and tests for thyroid function and RA-specific autoantibodies. The primary outcome was the presence or absence of thyroid disorders. RESULTS: A total of 158 RA patients were included. Eighty-five patients (53.8%) were seropositive, including 65 (41.1%) positive for rheumatoid factor and 58 (36.7%) positive for anti–citrullinated protein antibody. Erythrocyte sedimentation rate was elevated in 108 (72%) patients and 28 (19%) patients had significant Disease Activity Score (DAS 28). Vitamin D deficiency was observed in 100 patients (66.7%). Sixteen percent of patients in this cohort had hypothyroidism and 4.2% had hyperthyroidism. Vitamin D deficiency was associated with hyperthyroidism (2.1% vs. 8.9%, P = 0.048). Vitamin D deficiency was not significantly linked to seropositive RA (50% vs. 60%, P = 0.247) but was significantly associated with higher DAS 28 (15% vs. 30%, P = 0.030). CONCLUSION: Our study provides insights into thyroid patterns in Saudi Arabian patients with RA, highlighting the role of Vitamin D in thyroid disorders and disease activity. CATEGORIES: Internal Medicine, Rheumatology.

Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study

ObjectivesTo investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumour necrosis factor...

Addressing dispersion in mis-measured multivariate binomial outcomes: A novel statistical approach for detecting differentially methylated regions in bisulfite sequencing data.

Motivated by a DNA methylation application, this article addresses the problem of fitting and inferring a multivariate binomial regression model for outcomes that are contaminated by errors and exhibit extra-parametric variations, also known as dispersion. While dispersion in univariate binomial regression has been extensively studied, addressing dispersion in the context of multivariate outcomes remains a complex and relatively unexplored task. The complexity arises from a noteworthy data characteristic observed in our motivating dataset: non-constant yet correlated dispersion across outcomes. To address this challenge and account for possible measurement error, we propose a novel hierarchical quasi-binomial varying coefficient mixed model, which enables flexible dispersion patterns through a combination of additive and multiplicative dispersion components. To maximize the Laplace-approximated quasi-likelihood of our model, we further develop a specialized two-stage expectation-maximization (EM) algorithm, where a plug-in estimate for the multiplicative scale parameter enhances the speed and stability of the EM iterations. Simulations demonstrated that our approach yields accurate inference for smooth covariate effects and exhibits excellent power in detecting non-zero effects. Additionally, we applied our proposed method to investigate the association between DNA methylation, measured across the genome through targeted custom capture sequencing of whole blood, and levels of anti-citrullinated protein antibodies (ACPA), a preclinical marker for rheumatoid arthritis (RA) risk. Our analysis revealed 23 significant genes that potentially contribute to ACPA-related differential methylation, highlighting the relevance of cell signaling and collagen metabolism in RA. We implemented our method in the R Bioconductor package called "SOMNiBUS."

The peculiar features, diversity and impact of citrulline-reactive autoantibodies.

Since entering the stage 25 years ago as a highly specific serological biomarker for rheumatoid arthritis, anti-citrullinatedprotein antibodies (ACPAs) have been a topic of extensive research. This hallmark B cell response arises years before disease onset, displays interpatient autoantigen variability, and is associated with poor clinical outcomes. Technological and scientific advances have revealed broad clonal diversity and intriguing features including high levels of somatic hypermutation, variable-domain N-linked glycosylation, hapten-like peptide interactions, and clone-specific multireactivity to citrullinated, carbamylated and acetylated epitopes. ACPAs have been found in different isotypes and subclasses, in both circulation and tissue, and are secreted by both plasmablasts and long-lived plasma cells. Notably, although some disease-promoting features have been reported, results now demonstrate that certain monoclonal ACPAs therapeutically block arthritis and inflammation in mouse models. A wealth of functional studies using patient-derived polyclonal and monoclonal antibodies have provided evidence for pathogenic and protective effects of ACPAs in the context of arthritis. To understand the roles of ACPAs, one needs to consider their immunological properties by incorporating different facets such as rheumatoid arthritis B cell biology, environmental triggers and chronic antigen exposure. The emerging picture points to a complex role of citrulline-reactive autoantibodies, in which the diversity and dynamics of antibody clones could determine clinical progression and manifestations.

Prevalence of Autoantibodies (ACPA) and Rheumatoid Factor among Rheumatoid Arthritis Patients in Sulaymaniyah

Background and objectives: Rheumatoid factor and anticitrullinated protein antibodies are the most characteristic autoantibodies for rheumatoid arthritis. Our aims were to evaluate the prevalence of Rheumatoid factor and anticitrullinated protein antibodies and their association with demographic and clinical characteristics of patients with RA. Methods: This is a cross-sectional study which was conducted at Rheumatology and Rehabilitation Center/Sulaymaniyah from February 2022 to November 2022. The study included patients with rheumatoid arthritis from both sexes. Socio-demographic and clinical data were collected. Enzyme linked immunosorbent assay was used to estimate serum levels of rheumatoid factor and anticitrullinated protein antibodies antibody titer. Results: The prevalence of rheumatoid factor was 72.61%. Each of high disease activity, mean DAS28 scores, rheumatoid nodules and deformities were significantly associated with rheumatoid factor positivity (P= 0.015, P= 0.025, P= 0.007 and P&lt;0.001, respectively). The prevalence of anticitrullinated protein antibodies was 68.87%. High disease activity, rheumatoid nodules and deformities were significantly associated with anticitrullinated protein antibodies (P= 0.014, P&lt;0.001 and P&lt;0.001, respectively). Conclusions: The prevalence of rheumatoid factor and anticitrullinated protein antibodies among patients with rheumatoid arthritis was within the global context. High disease activity and the presence of rheumatoid nodules are positively associated with rheumatoid factor-positivity. Number of tender joints and the presence of rheumatoid nodules were positively associated with anticitrullinated protein antibodies-positivity.