Antibodies against human endogenous retrovirus K102 envelope activate neutrophils in systemic lupus erythematosus | Zendy

Maria Tokuyama | Zendy; Bronwyn M. Gunn | Zendy; Arvind Venkataraman | Zendy; Yong Kong | Zendy; Insoo Kang | Zendy; Tasfia Rakib | Zendy; Michael J. Townsend | Zendy; Karen H. Costenbader | Zendy; Galit Alter | Zendy; Akiko Iwasaki | Zendy

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Antibodies against human endogenous retrovirus K102 envelope activate neutrophils in systemic lupus erythematosus

Author(s) -

Maria Tokuyama,

Bronwyn M. Gunn,

Arvind Venkataraman,

Yong Kong,

Insoo Kang,

Tasfia Rakib,

Michael J. Townsend,

Karen H. Costenbader,

Galit Alter,

Akiko Iwasaki

Publication year - 2021

Publication title -

the journal of experimental medicine

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 8.483

H-Index - 448

eISSN - 1540-9538

pISSN - 0022-1007

DOI - 10.1084/jem.20191766

Subject(s) - neutrophil extracellular traps , immunology , immune system , endogenous retrovirus , autoantibody , innate immune system , antibody , biology , neutrophil elastase , immune complex , inflammation , gene , biochemistry , genome

Neutrophil activation and the formation of neutrophil extracellular traps (NETs) are hallmarks of innate immune activation in systemic lupus erythematosus (SLE). Here we report that the expression of an endogenous retrovirus (ERV) locus ERV-K102, encoding an envelope protein, was significantly elevated in SLE patient blood and correlated with autoantibody levels and higher interferon status. Induction of ERV-K102 in SLE negatively correlated with the expression of epigenetic silencing factors. Anti-ERV-K102 IgG levels in SLE plasma correlated with higher interferon stimulated gene expression, and further promoted enhanced neutrophil phagocytosis of ERV-K102 envelope protein through immune complex formation. Finally, phagocytosis of ERV-K102 immune complexes resulted in the formation of NETs consisting of DNA, neutrophil elastase, and citrullinated histone H3. Together, we identified an immunostimulatory ERV-K envelope protein that in an immune complex with SLE IgG is capable of activating neutrophils.

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