Alpha 1 Antitrypsin Gene Therapy Extends the Lifespan of Lupus-Prone Mice

Ahmed Samir Elshikha, Ye Yuan, Yuanqing Lu, Mong Jen Chen, Georges Abboud, Mohammad Ahsanul Akbar, Henrike Plate, Hedwig Wolney, Tanja Hoffmann, Eleni Tagari, Leilani Zeumer, Laurence Morel, Sihong Song

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by high levels of pathogenic autoantibodies and tissue damage. Multiple studies showed that dendritic cell (DC) activation plays a critical role in SLE pathogenesis. Human alpha 1 antitrypsin (hAAT) is a serine proteinase inhibitor with potent anti-inflammatory and cytoprotective properties. In this study, we first examined the effects of hAAT on the functions of DCs from lupus-prone mice, and we showed that hAAT treatment efficiently inhibited CpG- (TLR9 agonist) induced activation of bone marrow-derived conventional and plasmacytoid DCs as well as the production of pro-inflammatory cytokines. The hAAT treatment also attenuated DC help for B cell proliferation and immunoglobulin M (IgM) production. We next tested the protective effect of hAAT protein and gene therapy using recombinant adeno-associated virus 8 (rAAV8-CB-hAAT) in a spontaneous lupus mouse model, and we showed that both treatments decreased autoantibody levels. Importantly, rAAV8-CB-hAAT did not induce an immune response to its transgene product (hAAT), but it showed more pronounced therapeutic effects in reducing urine protein levels and extending the lifespan of these mice. These results indicate that AAT has therapeutic potential in the treatment of SLE in humans.

Original languageEnglish (US)
Pages (from-to)131-142
Number of pages12
JournalMolecular Therapy Methods and Clinical Development
StatePublished - Dec 14 2018
Externally publishedYes


  • AAT
  • DCs
  • SLE
  • alpha 1 antitrypsin
  • autoantibodies
  • autoimmunity
  • dendritic cells
  • life span
  • rAAV
  • systemic lupus erythematosus

ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Molecular Biology


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