Anthony Chang1, Marcus R Clark2, Kichul Ko2. 1. Department of Pathology. 2. Section of Rheumatology, Department of Medicine and Gwenn Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois, USA.
Abstract
PURPOSE OF REVIEW: Lupus nephritis is a common severe manifestation of systemic lupus erythematosus. Despite recent advances in therapeutics and understanding of its pathogenesis, there are still substantial unmet needs. This review discusses recent discoveries in these areas, especially the role of tubulointerstitial inflammation (TII) in lupus nephritis. RECENT FINDINGS: Non-white ethnicity is still a major risk and poor prognostic factor in lupus nephritis. TII and fibrosis have been found to be associated with worse renal outcome but the current lupus nephritis treatment guidelines and trials are based on the degree of glomerular inflammation. In combination with mycophenolate mofetil, a B-cell-targeted therapy (belimumab) and a calcineurin inhibitor (voclosporin) have shown efficacy in recent lupus nephritis trials. However, response rates have been modest. While lupus glomerulonephritis results from immune complex deposition derived from systemic autoantibodies, TII arises from complex processes associated with in situ adaptive cell networks. These include local antibody production, and cognate or antigen-induced interactions between T follicular helper cells, and likely other T-cell populations, with antigen presenting cells including B cells, myeloid dendritic cells and plasmacytoid dendritic cells. SUMMARY: Better understanding of the pathogenesis of TII will identify novel therapeutic targets predicted to improve outcomes in our patients with lupus nephritis.
PURPOSE OF REVIEW: Lupus nephritis is a common severe manifestation of systemic lupus erythematosus. Despite recent advances in therapeutics and understanding of its pathogenesis, there are still substantial unmet needs. This review discusses recent discoveries in these areas, especially the role of tubulointerstitial inflammation (TII) in lupus nephritis. RECENT FINDINGS: Non-white ethnicity is still a major risk and poor prognostic factor in lupus nephritis. TII and fibrosis have been found to be associated with worse renal outcome but the current lupus nephritis treatment guidelines and trials are based on the degree of glomerular inflammation. In combination with mycophenolate mofetil, a B-cell-targeted therapy (belimumab) and a calcineurin inhibitor (voclosporin) have shown efficacy in recent lupus nephritis trials. However, response rates have been modest. While lupus glomerulonephritis results from immune complex deposition derived from systemic autoantibodies, TII arises from complex processes associated with in situ adaptive cell networks. These include local antibody production, and cognate or antigen-induced interactions between T follicular helper cells, and likely other T-cell populations, with antigen presenting cells including B cells, myeloid dendritic cells and plasmacytoid dendritic cells. SUMMARY: Better understanding of the pathogenesis of TII will identify novel therapeutic targets predicted to improve outcomes in our patients with lupus nephritis.
Authors: Gabriel D Victora; Tanja A Schwickert; David R Fooksman; Alice O Kamphorst; Michael Meyer-Hermann; Michael L Dustin; Michel C Nussenzweig Journal: Cell Date: 2010-11-12 Impact factor: 41.582
Authors: Anthony Chang; Scott G Henderson; Daniel Brandt; Ni Liu; Riteesha Guttikonda; Christine Hsieh; Natasha Kaverina; Tammy O Utset; Shane M Meehan; Richard J Quigg; Eric Meffre; Marcus R Clark Journal: J Immunol Date: 2010-12-27 Impact factor: 5.422
Authors: R Graham Barr; Stephen Seliger; Gerald B Appel; Ricardo Zuniga; Vivette D'Agati; Jane Salmon; Jai Radhakrishnan Journal: Nephrol Dial Transplant Date: 2003-10 Impact factor: 5.992
Authors: Vladimir M Liarski; Adam Sibley; Nicholas van Panhuys; Junting Ai; Anthony Chang; Domenick Kennedy; Maria Merolle; Ronald N Germain; Maryellen L Giger; Marcus R Clark Journal: Nat Immunol Date: 2019-02-18 Impact factor: 25.606
Authors: Rebecca Abraham; Madeleine S Durkee; Junting Ai; Margaret Veselits; Gabriel Casella; Yuta Asano; Anthony Chang; Kichul Ko; Charles Oshinsky; Emily Peninger; Maryellen L Giger; Marcus R Clark Journal: J Clin Invest Date: 2022-07-01 Impact factor: 19.456