Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis

Chandra Mohan, Chaim Putterman

Research output: Contribution to journalReview articlepeer-review

279 Scopus citations


Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder that has a broad spectrum of effects on the majority of organs, including the kidneys. Approximately 40-70% of patients with SLE will develop lupus nephritis. Renal assault during SLE is initiated by genes that breach immune tolerance and promote autoantibody production. These genes might act in concert with other genetic factors that augment innate immune signalling and IFN-I production, which in turn can generate an influx of effector leucocytes, inflammatory mediators and autoantibodies into end organs, such as the kidneys. The presence of cognate antigens in the glomerular matrix, together with intrinsic molecular abnormalities in resident renal cells, might further accentuate disease progression. This Review discusses the genetic insights and molecular mechanisms for key pathogenic contributors in SLE and lupus nephritis. We have categorized the genes identified in human studies of SLE into one of four pathogenic events that lead to lupus nephritis. We selected these categories on the basis of the cell types in which these genes are expressed, and the emerging paradigms of SLE pathogenesis arising from murine models. Deciphering the molecular basis of SLE and/or lupus nephritis in each patient will help physicians to tailor specific therapies.

Original languageEnglish
Pages (from-to)329-341
Number of pages13
JournalNature Reviews Nephrology
Issue number6
StatePublished - 28 Jun 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.


The authors would like to acknowledge the editorial assistance of Simanta Pathak, University of Houston, USA. Relevant studies in Dr. Putterman’s laboratory were supported by grants from the NIH, DK090319 and AR048692. Dr. Putterman is currently a Weston Visiting Professor at the Weizmann Institute.

FundersFunder number
National Institutes of HealthDK090319
National Institute of Arthritis and Musculoskeletal and Skin DiseasesR56AR048692


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