The Relationship Between Serum Chemokine Ligand 21 (CCL-21) Level and Disease Activity

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.

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.

Eligibility Criteria:
Inclusion Criteria:

* 20 RA patients, 20 Osteoarthritis patients and 20 healthy volunteers between the ages of 16-60.

Exclusion Criteria:

* 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.