Role of Chemokines and Proinflammatory Cytokines in Rheumatoid Synovial Pathological Changes

This study has been withdrawn prior to enrollment.
(NO available budget and difficulty in recruiting)
Sponsor:
Information provided by (Responsible Party):
Chien-Sheng Wu, Far Eastern Memorial Hospital
ClinicalTrials.gov Identifier:
NCT00845949
First received: March 3, 2008
Last updated: May 18, 2012
Last verified: May 2012
  Purpose

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.


Condition
Rheumatoid Arthritis

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Role of Chemokines and Proinflammatory Cytokines in Rheumatoid Synovial Pathological Changes

Resource links provided by NLM:


Further study details as provided by Far Eastern Memorial Hospital:

Biospecimen Retention:   Samples With DNA

Synovial tissue


Enrollment: 0
Study Start Date: November 2006
Estimated Study Completion Date: June 2008
Estimated Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

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

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

-

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00845949

Locations
Taiwan
Division of Allergy, Autoimmunity and Rheuamtology, Department of Internal Medicine, Far Eastern Memorial Hospital
Pan-Chiao, Taiwan, 220
Sponsors and Collaborators
Far Eastern Memorial Hospital
Investigators
Principal Investigator: Chien-Sheng Wu Division of Allergy, Autimmunity and Rheumatology, Department of Internal Medicine
  More Information

No publications provided

Responsible Party: Chien-Sheng Wu, Chief, Division of Rheumatology, Far Eastern Memorial Hospital
ClinicalTrials.gov Identifier: NCT00845949     History of Changes
Other Study ID Numbers: 95034
Study First Received: March 3, 2008
Last Updated: May 18, 2012
Health Authority: Taiwan: Department of Health

Keywords provided by Far Eastern Memorial Hospital:
chemokines synovium

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on August 27, 2014