The anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) comprise a group of systemic autoimmune disorders characterized by the presence of autoantibodies against either proteinase 3 (Pr3) or myeloperoxidase (MPO). The overarching objective of our research is to investigate whether aberrations in B cell function promote pathogenic innate and adaptive immune responses in AAV both during disease induction and relapse. Investigations focus on potential B cell dysregulation in AAV that can manifest as 1) a disturbed balance in pro- and anti-inflammatory cytokine production by an imbalance in B cell subsets 2) aberrant selection, activation and maintenance of autoreactive B cells in lymphoid and inflamed tissues 3) predominance of pathogenic antibody epitope specificity and 4) aberrant glycosylation of IgG Fc and Fab regions of ANCA that influence their pathogenicity. With the obtained knowledge, we aim to improve disease monitoring, enable prevention of relapse and identify more specific therapeutic strategies.
Dept of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The Netherlands
Land J, Lintermans LL, Stegeman CA, Munoz-Elias EJ, Tarcha EJ, Iadonato SP, Heeringa P, Rutgers A, Abdulahad WH. Kv1.3 Channel Blockade Modulates the Effector Function of B Cells in Granulomatosis with Polyangiitis. Front Immunol. 2017.
Lepse N, Land J, Rutgers A, Kallenberg CG, Stegeman CA, Abdulahad WH, Heeringa P. Toll-like receptor 9 activation enhances B cell activating factor and interleukin-21 induced anti-proteinase 3 autoantibody production in vitro. Rheumatology (Oxford). 2016.
Land J, Abdulahad WH, Sanders JS, Stegeman CA, Heeringa P, Rutgers A. Regulatory and effector B cell cytokine production in patients with relapsing granulomatosis with polyangiitis. Arthritis Res Ther. 2016.
Lepse N, Abdulahad WH, Rutgers A, Kallenberg CG, Stegeman CA, Heeringa P. Altered B cell balance, but unaffected B cell capacity to limit monocyte activation in anti-neutrophil cytoplasmic antibody-associated vasculitis in remission. Rheumatology (Oxford). 2014.
Roth AJ, Ooi JD, Hess JJ, van Timmeren MM, Berg EA, Poulton CE, McGregor J, Burkart M, Hogan SL, Hu Y, et al. Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis. J Clin Invest. 2013.
van Timmeren MM, van der Veen BS, Stegeman CA, Petersen AH, Hellmark T, Collin M, Heeringa P. IgG glycan hydrolysis attenuates ANCA-mediated glomerulonephritis. J Am Soc Nephrol. 2010.
J. Land: B cell phenotype and function in granulomatosis with polyangiitis: Towards prediction of relapse. Awarded: 2016
N. Lepse: The regulatory and effector functions of B cells in ANCA-associated vasculitis. Awarded: 2014
Current PhD projects
G.J. Dekkema: miRNAs in ANCA associated vasculitis; regulators of aberrant T and B cell function?
A. von Borstel: B cells in small vessel vasculitis: towards balance between regulators and effectors