Rhea Bhargava1, George C Tsokos. 1. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Abstract
PURPOSE OF REVIEW: Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus and is characterized by proteinuria and renal failure. Proteinuria is a marker of poor prognosis and is attributed to podocyte loss and dysfunction. It is often debated whether these cells are innocent bystanders or active participants in the pathogenesis of glomerulonephritis. RECENT FINDINGS: Podocytes share many elements of the innate and adaptive immune system. Specifically, they produce and express complement components and receptors which when dysregulated appear to contribute to podocyte damage and LN. In parallel, podocytes express major histocompatibility complex and co-stimulatory molecules which may be involved in local immune events. Podocyte-specific cytotoxic cells and possibly other immune cells contribute to glomerular damage. Autoantibodies present in lupus sera enter podocytes to upregulate calcium/calmodulin kinase which in turn compromises their structure and function. SUMMARY: More recent studies point to the restoration of podocyte function using cell targeted approaches to prevent and treat LN. These strategies along with podocyte involvement in the pathogenesis of LN will be addressed in this review.
PURPOSE OF REVIEW: Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus and is characterized by proteinuria and renal failure. Proteinuria is a marker of poor prognosis and is attributed to podocyte loss and dysfunction. It is often debated whether these cells are innocent bystanders or active participants in the pathogenesis of glomerulonephritis. RECENT FINDINGS: Podocytes share many elements of the innate and adaptive immune system. Specifically, they produce and express complement components and receptors which when dysregulated appear to contribute to podocyte damage and LN. In parallel, podocytes express major histocompatibility complex and co-stimulatory molecules which may be involved in local immune events. Podocyte-specific cytotoxic cells and possibly other immune cells contribute to glomerular damage. Autoantibodies present in lupus sera enter podocytes to upregulate calcium/calmodulin kinase which in turn compromises their structure and function. SUMMARY: More recent studies point to the restoration of podocyte function using cell targeted approaches to prevent and treat LN. These strategies along with podocyte involvement in the pathogenesis of LN will be addressed in this review.
Authors: Bilal Hussain; Vivek Kasinath; Joren C Madsen; Jonathan Bromberg; Stefan G Tullius; Reza Abdi Journal: ACS Nano Date: 2021-10-29 Impact factor: 18.027
Authors: Anne K Mühlig; Lindsay S Keir; Jana C Abt; Hannah S Heidelbach; Rachel Horton; Gavin I Welsh; Catherine Meyer-Schwesinger; Christoph Licht; Richard J Coward; Lars Fester; Moin A Saleem; Jun Oh Journal: Front Immunol Date: 2020-08-14 Impact factor: 7.561
Authors: Rhea Bhargava; Sylvain Lehoux; Kayaho Maeda; Maria G Tsokos; Suzanne Krishfield; Lena Ellezian; Martin Pollak; Isaac E Stillman; Richard D Cummings; George C Tsokos Journal: JCI Insight Date: 2021-05-10