Role of TWEAK in lupus nephritis: A bench-to-bedside review

Jennifer S. Michaelson, Nicolas Wisniacki, Linda C. Burkly, Chaim Putterman

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

There is significant unmet need in the treatment of lupus nephritis (LN) patients. In this review, we highlight the role of the TWEAK/Fn14 pathway in mediating key pathologic processes underlying LN involving both glomerular and tubular injury, and thus the potential for renal protection via blockade of this pathway. The specific pathological mechanisms of TWEAK - namely promoting inflammation, renal cell proliferation and apoptosis, vascular activation and fibrosis - are described, with supporting data from animal models and in vitro systems. Furthermore, we detail the translational relevance of these mechanisms to clinical readouts in human LN. We present the opportunity for an anti-TWEAK therapeutic as a renal protective agent to improve efficacy relative to current standard of care treatments hopefully without increased safety risk, and highlight a phase II trial with BIIB023, an anti-TWEAK neutralizing antibody, designed to assess efficacy in LN patients. Taken together, targeting the TWEAK/Fn14 axis represents a potential new therapeutic paradigm for achieving renal protection in LN patients.

Original languageEnglish (US)
Pages (from-to)130-142
Number of pages13
JournalJournal of Autoimmunity
Volume39
Issue number3
DOIs
StatePublished - Sep 2012

Fingerprint

Lupus Nephritis
Kidney
Renal Agents
Protective Agents
Pathologic Processes
Therapeutics
Standard of Care
Neutralizing Antibodies
Blood Vessels
Fibrosis
Animal Models
Cell Proliferation
Apoptosis
Inflammation
Safety
Wounds and Injuries

Keywords

  • Fn14
  • Lupus nephritis
  • SLE
  • TWEAK

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Role of TWEAK in lupus nephritis : A bench-to-bedside review. / Michaelson, Jennifer S.; Wisniacki, Nicolas; Burkly, Linda C.; Putterman, Chaim.

In: Journal of Autoimmunity, Vol. 39, No. 3, 09.2012, p. 130-142.

Research output: Contribution to journalArticle

Michaelson, Jennifer S. ; Wisniacki, Nicolas ; Burkly, Linda C. ; Putterman, Chaim. / Role of TWEAK in lupus nephritis : A bench-to-bedside review. In: Journal of Autoimmunity. 2012 ; Vol. 39, No. 3. pp. 130-142.
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