Off balance: Regulatory and effector T cells in the pathogenesis of ANCA associated vasculitis

Anti-neutrophil cytoplasmatic auto-antibody (ANCA) associated vasculitis (AAV) are a group of systemic autoimmune diseases in which small to medium sized vessels are inflamed. Although the disease etiology is not fully understood, it has been shown that T lymphocytes play a major role in the pathogenesis. In this thesis Dekkema studied the balance between regulatory T (Tregs) and effector T (Teffs) cells in AAV. In this thesis, Dekkema studied why Tregs in AAV have a diminished suppressive function and found that this is partly due to increased expression of microRNAs. microRNAs can inhibit protein synthesis. Tregs of AAV patients had higher levels of miR-142-3p which led to diminished function. Interestingly, the diminished function due to miR-142-3p overexpression could be restored in vitro with Treg stimulating medication. Moreover, also the expression of markers on Tregs, which are also important for their function, were changed. Tregs of patients that experienced a relapse within one year after sampling, the expression of CCR5 was significantly lowered. This offers a new opportunity to monitor disease activity. Besides Tregs, Teffs play an important role in active disease, markers originated from Teffs can be found in blood and urine. The detection of soluble CD25 in urine and blood was found to be an important marker for active renal disease. All in all, the work presented in this thesis contributes to the knowledge of Tregs and Teffs in ANCA vasculitis and might offer new options in the detection, follow up and treatment