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IMMUNOPATHOGENESIS AND IMMUNITHERAPY OF CHRONIC ARTHRITIS

Objective


Four areas of research into immunotherapy of chronic arthritis are as follows:

immunogenetics:
A group in the United Kingdom has established a bank of Epstein-Barr virus (EBV) transformed B cell lines from rheumatoid multiplex families. This will allow the comprehensive analysis of genetic factors in this disease, and should open many possibilities for diagnostic and therapeutic intervention. A bank of human leucocyte antigen (HLA) class II transfectants is also being constituted.

T-cell biology:
Various groups have reported on clinical trials performed with CD4 antibodies in patients with rheumatoid arthritis. The newest development concerns administration of a monoclonal murine antibody chimerised with a human immunoglobulin G1 (IgG1) constant region. The antibody appears to be well tolerated and to induce T-cell cytopenia to various degrees. Another approach, very successful in animal models, is therapeutic T-cell vaccination.

Triggering and target antigens:
Research suggests that synoviocytes might incorporate and process antigens, thus clearing them very efficiently. This clearance activity would be impaired following adjuvant immunisation and would allow overexpression of autoantigens in the joints in the early stages of adjuvant arthritis. Another group working in this research area has produced direct evidence of cross reactivity between the human protein lactoferrin and the 65 kilodalton heat shock protein of Mycobacterium tuberculosis and M leprae.

Cytokines:
Addition of interleukin-4 (IL-4) to synovial cells has been found to results in down regualtion of IL-6 production. This makes IL-4 an interesting candidate for experimental therapeutic trials, planned in a Rhesus monkey model.

Funding Scheme

CON - Coordination of research actions

Coordinator

LEIDEN UNIVERSITY
Address
72,Rapenburg 70
2311 EZ Leiden
Netherlands