Immunogenesis and pathogenesis ANCA-mediated vasculitis


Contacts: Peter Heeringa

 

Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated small vessel vasculitides are rare, but life-threatening, systemic inflammatory diseases that affect small- to medium-sized blood vessels. Patients suffering from this disease have circulating autoantibodies that are directed against enzymes present in the neutrophils: myeloperoxidase or proteinase 3. Although multiple different organs can be affected, the lungs and kidneys are often involved. Involvement of the kidneys results in crescentic glomerulonephritis (=inflammation of the blood filtering units in the kidney, the glomeruli). It has been uncertain for a long time if ANCA are pathogenic and cause the underlying vasculitis. But, over the last decades increasing clinical and experimental evidence indicates that ANCA are causally involved in disease pathogenesis. However, the exact mechanism of disease initiation and progression is still unknown.

 

The aim of this project is to gain new insights into the pathogenesis of ANCA vasculitis and to identify key pathways and mediators involved in disease progression. To do this, patient oriented research combined with in vitro techniques and animal models for anti-MPO IgG-mediated glomerulonephritis will be used.

 

Our projects focus on the following research Questions:

  • What are the triggers for induction and re-activation of ANCA-associated vasculitides?
  • Which features of ANCA determine their pathogenicity?
  • Which are key immunological pathways and mediators involved in the initiation and progression of ANCA-associated vasculitides?
  • What are potential new targets for intervention, and evaluate the efficacy of new interventions.

 

The research is executed within The Vasculitis Expertise Center Groningen which comprises clinician scientists and basic scientists from the departments of Nephrology, Pathology and Medical Biology and Rheumatology and Clinical Immunology. The center is a nationally and internationally recognized expertise center that aims to provide vasculitis patients the best possible care and to perform state-of–the-art (translational) research. The center has particular expertise in large vessel vasculitis (LVV) and ANCA associated small-vessel vasculitides (AAV). Research within the “Vasculitis Expertise Center” focuses on both clinical and translational research and has made significant contributions to the diagnosis, treatment and understanding of the pathogenesis of vasculitis. Members of the center have performed long-term prospective studies to demonstrate the diagnostic sensitivity and specificity of antigenspecific ANCAs and the importance of ANCA-testing in the follow-up of patients with AAV. The pathogenic role of autoreactive T cell responses and of ANCA mediated effector pathways has been studied in great detail employing in vitro systems and unique animal models. Therapeutic studies have led to important improvements in the treatment of vasculitis and members have participated in major controlled trials, including clinical trials on the effects of B cell depletion in AAV (RAVE study) and IL6R blockade in LVV (GiACTA study). In summary, translational research from the Vasculitis Expertise Center Groningen has importantly contributed to the understanding of vasculitis pathogenesis, improved clinical monitoring of disease activity and improved treatment of vasculitis.



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Ingrid (G.) Molema

Professor of Life Sciences / EBVDT Group Leader

University Medical Center Groningen (UMCG)

Dept. Pathology and Medical Biology, Medical Biology section

 

Room T2.228

Internal postal code: EA11

Hanzeplein 1

9713 GZ Groningen

The Netherlands

Telephone: +31-50-3610115

Fax: +31-50-3619911

Email: g.molema01@umcg.nl

 

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