des Arbeitsbereichs Rheumatoide Arthritis im Kompetenznetz Rheuma

Rheumatoid Arthritis Research Section

Central to the research section is the establishment of a biomaterial bank from a multi-center nation-wide study on early rheumatoid arthritis (Harald Burkhardt, Frankfurt). Until now, three-year longitudinal observations on 354 patients with early RA (disease duration < 1 year) are completed and DNA (~400) as well as serum samples (~1500) have been collected. The data and material bank serves as a platform for several projects in this research section. The samples have been recently relocated from Erlangen to Frankfurt as Harald Burkhardt, who is in charge of the bank, has moved to Frankfurt.

In collaboration with researchers in and outside the network sera, DNA-samples and clinical data were used to investigate new serological parameters of early RA, as well as genetic factors that are related to different aspects of the pathogenesis of RA. For example, DNA-samples of the RA-inception cohort were made available to an external project (principal investigator: Prof. R. Straub, Regensburg) on genetic polymorphisms in the pathway of glucocorticoid metabolism after a respective application for the use of the material had been approved by the coordinating committee of the network. This study is still ongoing.

Other studies that were performed on the biomaterial of the RA inception cohort within the network resulted in the identification of

1. RA-specific autoantibody responses to citrullinated collagen type II in >40% of patients with recent onset RA demonostrating the immunogenicity of posttranslationally modified cartilage constituents;
   
   
2. an association of the SNP PTPN22*620W representing a functional mutation of a lymphocyte receptor associated phosphatase with the early humoral immune response to an arthritogenic B cell determinant in collagen type II.

Moreover, a synergism of this predisposing genetic factor with the RA-associated HLA-DRB1 alleles (”shared epitope”) on the early CII-autoantibody response could be demonstrated as well as its association with early joint erosions; and (iii) the identification of an SNP on the IL-4 receptor that is highly predictive for erosive disease.

Current funding mainly permitted the maintenance of the biomaterial bank on early RA and the transfer of the bank from Erlangen to Frankfurt.

In order to increase the sample numbers in the bank, efforts have been undertaken to recruit samples from major private rheumatology offices throughout Germany. These efforts were successful in several places.
A major goal of ongoing research with the material from the bank is to identify prognostic markers for disease activity, the course of the disease (erosive vs. non-erosive) and the outcome of particular medical treatment. The material has contributed to several publications and patent applications. A second goal of the ongoing work is to link the database with a biomaterial bank of local joint pathology, that is currently developed by Thomas Pap, Munster.

Using the new biomaterial bank of local joint pathology, efforts are undertaken to standardize and certify local joint pathology at the level of EULAR standards.
The research section RA coordinates its efforts on the identification of biomarkers in RA with ofther federal funding programs, such as the national genom research network.