Serum Anti-PCOLCE as Novel Diagnostic Biomarker in Rheumatoid Arthritis With Emphasis on Seronegative Patients.
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Clinical evaluation, disease activity and disability scoring, and laboratory testing including RF, anti-CCP, and serum anti-PCOLCE antibody measurement by ELISA..
- Who it may be relevant to
- Registry conditions: Rheumatoid Arthritis. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Center list to be confirmed — check the primary protocol.
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects synovial joints, leading to pain, swelling, and progressive joint damage. Early diagnosis is critical to prevent irreversible disability. However, up to 30% of RA patients are seronegative for conventional markers such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, creating a diagnostic challenge. This study aims to evaluate the diagnostic performance of serum anti-procollagen C-endopeptidase enhancer (anti-PCOLCE) antibodies in RA patients, with a particular focus on seronegative cases. We will conduct a case-control study involving RA patients and age- and sex-matched healthy controls. Clinical assessments, disease activity scoring, functional disability evaluation, and laboratory testing will be performed. The findings may provide evidence for anti-PCOLCE as a novel biomarker for improved RA diagnosis.
Detailed description
Rheumatoid arthritis (RA) is an inflammatory disease that primarily affects synovial joints through an autoimmune mechanism. If not treated properly, the disease can lead to bone erosion, joint deformities, and disability. Arthritis can also cause serious extra-articular disorders, including interstitial lung disease, vasculitis, and lymphoma.
The global prevalence of RA is 1%, with 44% of patients incapacitated within ten years. Increasing evidence indicates that early diagnosis and treatment of RA are crucial in preventing or delaying progression to erosive disease.
The production of antibodies to modified self-antigens is a hallmark in RA damage to synovial joints. The diagnosis of RA is based on a combination of clinical, radiographic, and serological findings. Among serological biomarkers, the most widely used are rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. While anti-CCP antibodies are relatively specific for RA and are included in the 2010 ACR/EULAR classification criteria, they are not present in all patients. Approximately 20-30% of RA patients may test negative for both RF and anti-CCP, is termed seronegative RA (SNRA) emphasizing the need for additional, more sensitive and specific biomarkers, especially in early and seronegative RA.
Antibodies to citrullinated and carbamylated proteins are of particular interest in RA because of their high prevalence, specificity, association with erosive disease, and appearance during the preclinical phase of RA. Citrullination is a physiological posttranslational modification (PTM) best known for its role in gene regulation and skin keratinization. During this process, arginine residues are converted to citrulline by the activity of the peptidylarginine deiminase (PAD) enzymes.
Procollagen C-protease enhancer protein (PCOLCE) is a secretory glycoprotein, which plays an important role in enhancing the activity of procollagen C-Protease and promoting the reconstruction of extracellular matrix.
PCOLCE essential for the maturation of collagen, particularly types I and II. These collagen types are major components of articular cartilage and connective tissues. In the inflammatory environment of RA, PCOLCE can undergo citrullination, potentially converting it into a novel autoantigen.
Emerging evidence suggests that PCOLCE may elicit an autoimmune response in RA patients. Detecting autoantibodies directed against PCOLCE (anti- PCOLCE ) could therefore provide a new serological tool for RA diagnosis. These antibodies may not only enhance diagnostic accuracy particularly in patients who are seronegative for conventional markers but also shed light on novel mechanisms in RA pathophysiology.
Interventions
- Diagnostic test Clinical evaluation, disease activity and disability scoring, and laboratory testing including RF, anti-CCP, and serum anti-PCOLCE antibody measurement by ELISA.
For rheumatoid arthritis (RA) patients: participants will undergo comprehensive clinical evaluation including demographic data, detailed history, musculoskeletal and systemic examination, assessment of disease activity using DAS-28 score, functional disability evaluation by modified Health Assessment Questionnaire (mHAQ), and laboratory investigations including CBC, ESR, CRP, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and serum anti-procollagen C-endopeptida
Primary outcome measures
- Serum anti-PCOLCE antibody levels in rheumatoid arthritis patients versus healthy controls [Time frame: Baseline (at the time of enrollment)]
- measure serum level of anticitrullinated procollagen C endopeptidase enhancer antibody (anti-PCOLCE) in RA patients compared to healthy controls . [Time frame: At baseline (single measurement at enrollment).]
Secondary outcome measures (1)
- Correlation between serum anti-PCOLCE antibody levels and disease activity scores in RA patients [Time frame: At baseline (single assessment at enrollment).]
Eligibility criteria
Inclusion criteria Adults (≥18 years old).
Patients clinically diagnosed with rheumatoid arthritis according to the 2010 ACR/EULAR classification criteria:
Exclusion criteria Patients with other autoimmune or connective tissue diseases (e.g., SLE, SS). Patients with chronic infections or malignancies. Patients less than 18 years old.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Case-control
Study locations
Center list to be confirmed — check the primary protocol.
Publications
- van der Woude D, Young A, Jayakumar K, Mertens BJ, Toes RE, van der Heijde D, Huizinga TW, van der Helm-van Mil AH. Prevalence of and predictive factors for sustained disease-modifying antirheumatic drug-free remission in rheumatoid arthritis: results from two large early arthritis cohorts. Arthritis Rheum. 2009 Aug;60(8):2262-71. doi: 10.1002/art.24661. PMID 19644846
- Figus FA, Piga M, Azzolin I, McConnell R, Iagnocco A. Rheumatoid arthritis: Extra-articular manifestations and comorbidities. Autoimmun Rev. 2021 Apr;20(4):102776. doi: 10.1016/j.autrev.2021.102776. Epub 2021 Feb 17. PMID 33609792
- Maska L, Anderson J, Michaud K. Measures of functional status and quality of life in rheumatoid arthritis: Health Assessment Questionnaire Disability Index (HAQ), Modified Health Assessment Questionnaire (MHAQ), Multidimensional Health Assessment Questionnaire (MDHAQ), Health Assessment Questionnaire II (HAQ-II), Improved Health Assessment Questionnaire (Improved HAQ), and Rheumatoid Arthritis Qua PMID 22588760
Identifiers
NCT: NCT07129837 · Anti-pcolce in RA