Role of Chemokines and Proinflammatory Cytokines in Rheumatoid Synovial Pathological Changes

Rheumatoid arthritis is a common chronic destructive arthritis. Major pathology change in rheumatoid arthritis is synovium hyperplasia with bone and cartilage erosion. Infiltrates in synovial tissue included type one and type two synoviocytes, B cells, T cells and fibroblasts. These cells will release many cytokines and chemokines, which will induce expression of adhesion molecules, release of variable enzyme from fibroblast and osteoclast and result in bone erosion.

Recent study revealed that fibroblast-like synoviocytes (FLS) have some role in pathogenesis of rheumatoid arthritis.We believed CXCL12/CXCR4 ligand/receptor pair is important in chronicity of rheumatoid arthritis.

CXCL12 polymorphism is studied in many disease. There is no related CXCL12 polymorphism study in rheumatoid arthritis. Our study intended to clarify the relationship between pathology, serology factor, CXCL12 polymorphism in rheumatoid arthritis in hope that new direction of therapy will be elucidated.

Study Overview

• Status: Withdrawn
• Conditions: Rheumatoid Arthritis

Detailed Description

Rheumatoid arthritis is a common chronic destructive arthritis. Many patients suffered from disability from this disease. There is no satisfactory therapy for every patient. Present prognostic factor only explained the disease course partially.

Major pathology change in rheumatoid arthritis is synovium hyperplasia with bone and cartilage erosion. Infiltrates in synovial tissue included type one and type two synoviocytes, B cells, T cells and fibroblasts. These cells will release many cytokines and chemokines, which will induce expression of adhesion molecules, release of variable enzyme from fibroblast and osteoclast and result in bone erosion.

Previous study in rheumatoid arthritis focused mainly in role of lymphocytes and osteoclast. Recent study revealed that fibroblast-like synoviocytes (FLS) have some property which is similar but not identical to dendritic cells in lymph nodes. They are also important provider of IL-7 and IL-15 and play an important role in persisted activation of synovial tissue. Fibroblast will guide B cell infiltration and has intimate mutual interaction with T cells.

Stromal derived growth factor/CXCL12 is an effective lymphocyte chemokine. CXCR4 is corresponding receptor. CXCL12 has been associated with autoantibody production in lupus murine model animal. FLS can express stromal cell-derived factor 1 SDF-1/CXCL12, inducing persisted infiltration of CD4+ and CD8+ T cell. Furthermore, migration, proliferation and matrix mental proteinase secretion of FLSis regulated by CC and CXC chemokine. CXCL12 production by SLF is regulated by TNF-alpha, IL-1beta, and TGF-beta1, but there is still some inconsistency in literatures. CXCL12 itself also induce expression of CXCR4 and secretion of IL-6, IL-8 in FLS. Express of CCR4 in T cell is regulated by IL-2,IL-4,IL-7,IL-10 and cell contact. CXCL12 produced by SLF is also presented by endothelium cell and inducing angiogenesis. Clinical study also indicated that CXCL12 level is related to cartilage destruction. CXCL12 level is decreased after synovectomy. Therefore we believed CXCL12/CXCR4 ligand/receptor pair is important in chronicity of rheumatoid arthritis.

Recently CXCL12 polymorphism is studied in many disease, such as prognosis of HIV patients、chronic myeloproliferative disease, and AML metastasis. There is no related CXCL12 polymorphism study in rheumatoid arthritis. Our study intended to clarify the relationship between pathology, serology factor, CXCL12 polymorphism in rheumatoid arthritis in hope that new direction of therapy will be elucidated.

• Study Type: Observational

Contacts and Locations

Study Locations

• Taiwan
  • Pan-Chiao, Taiwan, 220
    • Division of Allergy, Autoimmunity and Rheuamtology, Department of Internal Medicine, Far Eastern Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Synovial tissue from patient with rheumatoid arthritis who underwent total knee replacement surgery after informed consent.

Description

Inclusion Criteria:

• patients with rheumatoid arthritis fulfills ACR 1987 classification criteria for rheumatoid arthritis

Exclusion Criteria:

-

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Collaborators and Investigators

• Sponsor: Far Eastern Memorial Hospital
• Investigators: Principal Investigator: Chien-Sheng Wu, Division of Allergy, Autimmunity and Rheumatology, Department of Internal Medicine

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Anticipated): June 1, 2008
• Study Completion (Anticipated): June 1, 2008

Study Registration Dates

• First Submitted: March 3, 2008
• First Submitted That Met QC Criteria: February 16, 2009
• First Posted (Estimate): February 18, 2009

Study Record Updates

• Last Update Posted (Estimate): May 21, 2012
• Last Update Submitted That Met QC Criteria: May 18, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: chemokines synovium
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: 95034