Chapter

Pathogenesis of lupus nephritis

N. Stanley Nahman and Michael P. Madaio

in Rheumatology and the Kidney

Second edition

Published on behalf of Oxford University Press

Published in print April 2012 | ISBN: 9780199579655
Published online February 2013 | e-ISBN: 9780191763472 | DOI: http://dx.doi.org/10.1093/med/9780199579655.003.0027

Series: Oxford Clinical Nephrology Series

Pathogenesis of lupus nephritis

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1. Autoreactive cells through direct infiltration and/or through their secretory products initiate inflammation in lupus nephritis. Immunological and non-immunological factors influence outcome in lupus nephritis, and these pathophysiological arms of renal damage represent therapeutic targets. 2. Cell-based destructive pathways include autoreactive T cells, B cells and macrophages manifesting with the production of pathological autoantibodies, immune complex formation, activation of complement and triggering of the local inflammatory cascade. In murine models, both the development and severity of nephritis are under the influence of multiple genes and both MHC and non-MHC loci and genes have been linked. 3. Glucocorticoids limit tissue infiltration of activated T cells by increasing apoptosis and suppressing proliferation. CTX, MMF and AZA inhibit cell-based inflammatory pathways by directly blocking production of T and B cells (e.g. in the bone marrow). 4. Rituximab is a chimeric monoclonal antibody against CD20 and is an effective depleter of B cells. 5. The most proximal step in the activation of small molecule-based immune-mediated pathways is the development of nephritogenic lupus autoantibodies that participate in the formation of immune deposits. The use of antagonists of individual cytokines or small molecules is based on the rationale that interruption of a specific pathological pathway will alleviate downstream inflammatory events and translate into improved clinical outcome. 6. Inhibitors of cytokines and small molecules of interest in the therapy of lupus nephritis include infliximab and etanercept (TNF), sifalimumab (anti-IFNα tocilizumab (IL-R receptor), epratuzumab (anti-CD22), belimumab (BLyS), abatacept (inhibits T cell co-stimulation of B cells), N-acetylcysteine (free radical scavenger), rapamycin (engages mTOR) and fostamatinib (Syk inhibitor). 7. Non-immunological disease progression in lupus manifests clinically as hypertension and proteinuria, both of which are treated using ACE inhibitors or ARBs.

Chapter.  7047 words. 

Subjects: Nephrology

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