des Arbeitsbereichs Immunvaskulitiden im Kompetenznetz Rheuma

Immunevasculitides Research Section

In the research section “Immunevasculitides” two banks with biological material were established and several studies were performed which are summarized here.

A) Clinical studies:

1. In the “LUKON” study, 43 SLE patients from 11 centers were randomized to be treated with either azathioprine or methotrexate to sustain remission after therapy with cyclophosphamide. The final evaluation of the study is currently being performed.
   
   
2. In a parallel study, predictors for infections were evaluated in patients treated with cyclophosphamide. As a result of this study, the Freiburg Infection Risk Score (IRS) was developed and is now available in the internet.
   
   
3. In the PREGO study, the efficacy of GnRH analogues to sustain gonadal function in females treated with cyclophosphamide was evaluated. 32 patients were recruited into the prospective study. The final evaluation is going on now.
   
   
4. In the „LEM“ study 54 patients with Wegener`s granulomatosis were randomized after induction therapy with cyclophosphamide to be treated with either 30 mg of leflunomide/day or up to 20 mg of methotrexate/week. Leflunomide proved to be significantly better in sustaining remission, so that the study was discontinued earlier than initially planned.

None of the clinical studies would have been possible without the multicenter character of the network. In exchange, all of the results have been presented to all the members of the network and will help to improve and standardize clinical procedures and therapeutic decisions.

B) Material banks

Two DNA banks were established, one with material from patients with ANCA+ vasculitides and a second with material from patients with SLE.

1. 320 patients with Wegener`s granulomatosis were recruited for the vasculitis DNA bank. Extensive characterization of risk genes of vasculitides is going on. So far, after genomewide microsatellite analysis, associations of Wegener's granulomatosis with the PTPN22 620W allele as well as with a gene in the chromosomal region 6p21.3 have been characterized.
   
   
2. In the SLE genetics project, 420 SLE patients and as controls 105 patients with scleroderma and 220 with primary Sjögren`s syndrome were recruited in collaboration with 7 university centers and several patient support groups. The bank is now being used for characterization of SLE susceptibility genes by three international and two German groups.  Several genes associated with autoimmune disorders (Trex-1, ILT6, NKG2D, IRF-5) have already been described. ILT6 has been patented for diagnostics and treatment of autoimmune disorders.

Both of the banks could not have established without the support of the competence net and the help of colleagues from other centers and patient groups.

C) Clinical applications of antineutrophil cytoplasmic antibody (ANCA) testing

Strategies for ANCA detection have been established; Quality assessment programs (i.e., evaluation of  the performance of commercial kits); Organisation of educational workshops (for personal from clinical laboratories and physicians) have been performed. Furthermore, 10 sera were sent to all the members of the section immunevasculitides for evaluation of presence of ANCA twice a year to standardize and improve ANCA tests within the competence net.

In the future, the members of the section immunevasculitides want to continue the successful collaborations and have decided to further enlarge the material banks and establish registers of patients with rare disorders such as Churg-Strauss syndrome, Hyper-Eosinophilic-Syndrome and Ormond`s disease. Furthermore, an inception cohort of SLE patients has been started and a study to compare biopsy with MR tomography in diagnostics of giant cell arteritis is being planned.