The Relationship Between Serum Chemokine Ligand 21 (CCL-21) Level and Disease Activity
- Conditions
- OsteoarthritisRheumatoid Arthritis
- Interventions
- Diagnostic Test: Laboratory tests (examination)Diagnostic Test: Western Ontario and McMaster Universities Osteoarthritis (WOMAC) IndexDiagnostic Test: The Disease Activity Score28 (DAS28)Diagnostic Test: Patient global assessment (PGA)Diagnostic Test: Physician global assessment (PhGA)Diagnostic Test: Health Assessment Questionnaire (HAQ)Diagnostic Test: Knee RadiographyDiagnostic Test: Clinical disease activity index (CDAI)Diagnostic Test: The Simplified Disease Activity Index (SDAI)
- Registration Number
- NCT06540573
- Lead Sponsor
- Gaziosmanpasa Research and Education Hospital
- Brief Summary
Rheumatoid arthritis (RA) is a chronic systemic disease characterized by the development of new capillaries involved in the infiltration of inflammatory cells causing synovial hyperplasia and progressive destruction of cartilage and bone.Osteoarthritis (OA) is a degenerative joint disease that involves articular cartilage and other intra-articular structures.Although the pathological mechanisms involved in OA and RA are different, the onset and progression of both diseases are associated with inflammation, immune mechanisms and metabolic factors.C-C Motif Chemokine Ligand 21 (CCL21) is a CCR7-binding chemokine that plays an important role by modulating the circulation of T cells and dendritic cells in lymphoid and peripheral organs (9). Ligation of CCL21 in RA fibroblasts and macrophages induced the production of proangiogenic factors such as VEGF, Ang-1, and IL-8, suggesting that CCL21 plays an indirect role in RA angiogenesis.The aim of our study is to evaluate the serum levels of CCL21 in RA and OA patients by comparing them with healthy controls. In addition, the aim is to examine the correlation of serum CCL21 with disease degree/severity in both diseases and to determine whether it can be a biomarker of the disease state.
- Detailed Description
Rheumatoid arthritis (RA) is a chronic systemic disease characterized by the development of new capillaries involved in the infiltration of inflammatory cells causing synovial hyperplasia and progressive destruction of cartilage and bone. The synovial tissue layer consists of macrophages and fibroblasts, which have profound effects on the destructive process in RA through the production of pro-inflammatory cytokines, chemokines and pro-angiogenic factors (2,3). Osteoarthritis (OA) is a degenerative joint disease that involves articular cartilage and other intra-articular structures (4). OA leads to pain, stiffness, decreased joint function (5), and ultimately disability (6). Although the pathological mechanisms involved in OA and RA are different, the onset and progression of both diseases are associated with inflammation, immune mechanisms and metabolic factors (7,8). C-C Motif Chemokine Ligand 21 (CCL21) is a CCR7-binding chemokine that plays an important role by modulating the circulation of T cells and dendritic cells in lymphoid and peripheral organs (9). Ligation of CCL21 in RA fibroblasts and macrophages induced the production of proangiogenic factors such as VEGF, Ang-1, and IL-8, suggesting that CCL21 plays an indirect role in RA angiogenesis ( 10 ).
We determined that CCL21-mediated RA arthritis extends joint inflammation to bone erosion by coupling the differentiation of M1 macrophages with Th17 cells. Disease progression is further exacerbated by CCL21-induced neovascularization. We conclude that CCL21 is an attractive new target for the treatment of RA, as blocking its function can abolish erosive arthritis modulated by M1 macrophages and Th17 cell crosstalk. In short, CCL21 is a pleiotropic chemokine that shapes many aspects of RA pathology. We have not found a study that examined CCL21 blood serum levels in RA and OA patients and healthy controls and evaluated whether there is a relationship between CCL21 and these diseases.
The aim of our study is to evaluate the serum levels of CCL21 in RA and OA patients by comparing them with healthy controls. In addition, the aim is to examine the correlation of serum CCL21 with disease degree/severity in both diseases and to determine whether it can be a biomarker of the disease state.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 60
- 20 RA patients, 20 Osteoarthritis patients and 20 healthy volunteers between the ages of 16-60.
- Age < 16 years,
- Systemic Disorders (Diabetes, Hematological diseases (coagulopathies), serious cardiovascular diseases, chronic liver and kidney disease or malignancy.)
- Patients suffering from infectious disorders (septic arthritis, viral arthritis, fungal arthritis and other rheumatic diseases such as spondyloarthropathies, systemic lupus erythematosus or dermatomyositis and others.)
- Individuals with other autoimmune diseases, malignancy, cardiac or neurological deficits, end-stage organ failure and other conditions that may affect the serum level of CCL21, such as diabetes mellitus, concomitant inflammatory disease (acute infection or chronic inflammatory state), coronary artery disease and hepatitis, were excluded from the study. was left
- Lymphadenopathies
- OA patients who received intra-articular injection or systemic glucocorticoid therapy within 3 months were excluded from the study.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Patients who were diagnosed with rheumatoid arthritis and applied to outpatient clinic Laboratory tests (examination) Patients diagnosed with rheumatoid arthritis (meeting the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria Patients who were diagnosed with osteoarthritis and applied to outpatient clinic Patient global assessment (PGA) Patients diagnosed with osteoarthritis (meeting the American College of Rheumatology (ACR) criteria Patients who were diagnosed with osteoarthritis and applied to outpatient clinic Knee Radiography Patients diagnosed with osteoarthritis (meeting the American College of Rheumatology (ACR) criteria Patients who were diagnosed with rheumatoid arthritis and applied to outpatient clinic The Simplified Disease Activity Index (SDAI) Patients diagnosed with rheumatoid arthritis (meeting the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria Patients who were diagnosed with osteoarthritis and applied to outpatient clinic Laboratory tests (examination) Patients diagnosed with osteoarthritis (meeting the American College of Rheumatology (ACR) criteria Patients who were diagnosed with osteoarthritis and applied to outpatient clinic Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Patients diagnosed with osteoarthritis (meeting the American College of Rheumatology (ACR) criteria Patients who were diagnosed with osteoarthritis and applied to outpatient clinic Physician global assessment (PhGA) Patients diagnosed with osteoarthritis (meeting the American College of Rheumatology (ACR) criteria Patients who were diagnosed with rheumatoid arthritis and applied to outpatient clinic Patient global assessment (PGA) Patients diagnosed with rheumatoid arthritis (meeting the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria Patients who were diagnosed with osteoarthritis and applied to outpatient clinic Health Assessment Questionnaire (HAQ) Patients diagnosed with osteoarthritis (meeting the American College of Rheumatology (ACR) criteria Patients who were diagnosed with rheumatoid arthritis and applied to outpatient clinic The Disease Activity Score28 (DAS28) Patients diagnosed with rheumatoid arthritis (meeting the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria Patients who were diagnosed with rheumatoid arthritis and applied to outpatient clinic Clinical disease activity index (CDAI) Patients diagnosed with rheumatoid arthritis (meeting the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria Healthy volunteers Laboratory tests (examination) Healthy who were volunteers applied to the physical treatment and rehabilitation outpatient clinic Patients who were diagnosed with rheumatoid arthritis and applied to outpatient clinic Physician global assessment (PhGA) Patients diagnosed with rheumatoid arthritis (meeting the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria Patients who were diagnosed with rheumatoid arthritis and applied to outpatient clinic Health Assessment Questionnaire (HAQ) Patients diagnosed with rheumatoid arthritis (meeting the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria Healthy volunteers Health Assessment Questionnaire (HAQ) Healthy who were volunteers applied to the physical treatment and rehabilitation outpatient clinic
- Primary Outcome Measures
Name Time Method Patient global assessment (PGA) Within 1 week of applying to outpatient clinic Patient global assessment (PGA) of disease activity will be reported by patients. PGA was developed in the late 1970s and was initially designed for the measurement of self-assessed pain in RA \[8\], although it has since been used to evaluate RA more globally. It is interesting to note that the way PGA is used in clinical practice covers, in fact, two very different concepts, one related to global health and the other to overall disease activity. They are both usually used under the heading of PGA without further specification for which is being assessed.
Health Assessment Questionnaire (HAQ) Within 1 week of applying to outpatient clinic Functional impairment will be assessed with the Health Assessment Questionnaire (HAQ). It is a self-assessment tool used to measure functional ability in eight different areas: rising, dressing and grooming, hygiene, eating, walking, reach, grip, and activities of independent living. Each item or question is rated on a scale of 0 to 3, with 0 (normal/no difficulty), 1 (some difficulty), 2 (much difficulty), and 3 (unable to do). The 8 category scores are averaged, which represent an overall score from 0 (no disability) to 3 (completely disabled). If the questionnaire is slightly changed to reflect a certain disease, this does not affect the respective scoring.Scores 0-1 indicates mild to moderate disability, 1-2 indicates moderate to severe disability, and 2-3 indicates severe to very severe disability.
Clinical disease activity index (CDAI) Within 1 week of applying to outpatient clinic Clinical Disease Activity Index (CDAI) is a composite index (without acute-phase reactant) for assessing disease activity. CDAI is based on the simple summation of the count of swollen/tender joint count of 28 joints along with patient and physician global assessment on VAS (0-10 cm) Scale for estimating disease activity. The CDAI has range from 0 to 76
The Disease Activity Score28 (DAS28) Within 1 week of applying to outpatient clinic The Disease Activity Score (DAS) was created as a numerical tool for quantifying and assessing disease activity in rheumatoid arthritis (RA).The DAS28 (Disease Activity Score using 28 joint counts) was developed from the original DAS (Disease Activity Score).The DAS28 evaluates the disease activity by assessing the number of tender and swollen joints in a patient. Specifically, it considers 28 joints. The DAS28 also takes into account a blood marker of inflammation, typically the erythrocyte sedimentation rate (ESR) or the C-reactive protein (CRP) level.A patient with a DAS28 score of less than 2.6 is in remission; a score greater than or equal to 2.6 and less than 3.1 indicates low activity; a score greater than or equal to 3.1 and \<5.1 indicates moderate activity and a score 5.1 or more indicates high activity
Physician global assessment (PhGA) Within 1 week of applying to outpatient clinic Physician global assessment (PhGA)of disease activity will be reported by the physician.The Physician Global Assessment (PhGA) of treatment response measures the overall response to treatment as assessed by the physician. The PhGA is a well accepted and commonly used scale for evaluating treatment response in clinical trials both in adults and children. PhGA is a simple instrument and the result is easily understood. However, assigning a score for PhGA requires a very detailed evaluation. To perform this assessment a physician/health care provider would use extensive data from every aspect of ICF.
Simplified Disease Activity Index Within 1 week of applying to outpatient clinic The Simplified Disease Activity Index for Rheumatoid Arthritis (SDAI) is a scoring system that has been validated in both research and clinical settings. It has been shown to have the highest sensitivity and specificity for predicting a physicians' decisions to change DMARD therapy when compared to other scores.Remission is defined as an SDAI of \<3.3, low disease activity as ≤11, moderate disease activity as ≤26 and high disease activity as \>26. Response to therapy is considered moderate if SDAI decreases by ≥7 and major if decreases by ≥17
- Secondary Outcome Measures
Name Time Method