Modulation of the B-cell repertoire in autoimmune diseases
Project management at the University of Würzburg:
Mechanisms contributing to the onset of an autoimmune disease are still not very well understood. Functional data provide good evidence for B-lymphocytes to be directly involved in the development and propagation of T-cell mediated autoimmunity besides the production of disease relevant antibodies. In addition, an altered use of variable immunoglobulin genes in autoimmune disease has been described. First clinical trials with patients suffering from rheumatoid arthritis (RA) document a marked reduction in the disease activity score after depletion of the CD20 positive B-cell pool.The first part of the proposal deals with the analysis of the Ig-VH repertoire i an extended group of patients suffering from connective tissue disorders or RA. This will be facilitated by using a specific multiplex PCR, which has been developed in the lab. We aim to define groups of patients with preferentially used Ig-VH genes of whom selected cases can be studied in more detail. The main focus, however, concerns the analysis of B-cell regeneration in patients with autoimmune disease, which have been treated with an anti-CD20 antibody. This will be done by analysing defined B-cell subopulations using a single cell PCR method. The clinical model allows to investigate an individual change of the immunoglobulin repertoire as well as an alteration of individual dominant Ig-VH genes after B-cell regeneration. The results can be correlated to the clinical response of the patient.
Projekt period: from 05.2002 to 04.2004