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

2021 ◽  
Vol 218 (7) ◽  
Author(s):  
Maria Tokuyama ◽  
Bronwyn M. Gunn ◽  
Arvind Venkataraman ◽  
Yong Kong ◽  
Insoo Kang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Complex ◽  
Lupus Erythematosus ◽  
Envelope Protein ◽  
Endogenous Retrovirus ◽  
Innate Immune ◽  
Human Endogenous Retrovirus ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Immune Complex Formation

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.

scholarly journals Antibody against envelope protein from human endogenous retrovirus activates neutrophils in systemic lupus erythematosus

2019 ◽  
Author(s):  
Maria Tokuyama ◽  
Bronwyn M. Gunn ◽  
Arvind Venkataraman ◽  
Yong Kong ◽  
Insoo Kang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Complex Formation ◽  
Immune Complex ◽  
Lupus Erythematosus ◽  
Envelope Protein ◽  
Endogenous Retrovirus ◽  
Neutrophil Activation ◽  
Systemic Lupus ◽  
Interferon Signature ◽  
Immune Complex Formation

AbstractNeutrophil activation and the formation of neutrophil extracellular trap (NET) are hallmarks of innate immune activation in systemic lupus erythematosus (SLE) and contribute to the systemic interferon signature. 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 was correlated with higher interferon status. Induction of ERV-K102 expression most strongly correlated with reduced transcript levels of epigenetic silencing factors. SLE IgG promoted phagocytosis of ERV-K102 envelope protein by neutrophils through immune complex formation. ERV immune complex phagocytosis resulted in subsequent NET formation consisting of DNA, neutrophil elastase, and citrullinated histone H3. Finally, analysis of anti-ERV-K102 IgG in SLE patients showed that IgG2 likely mediates this effect. Together, we identified an immunostimulatory ERV-K envelope protein elevated in SLE that may be a target of SLE IgG and able to promote neutrophil activation.eTOC summaryUsing ERVmap, the authors determined that the expression of ERV-K102 locus was elevated in SLE patient blood and correlated with the interferon signature. The envelope protein encoded by this locus activates human neutrophils through immune complex formation with SLE IgG.

Polymorphic genotypes of the HRES-1 human endogenous retrovirus locus correlate with systemic lupus erythematosus and autoreactivity

1999 ◽  
Vol 49 (10) ◽  
pp. 829-834 ◽  
Author(s):  
Claudio Magistrelli ◽  
Ella Samoilova ◽  
Rajeev K. Agarwal ◽  
Katalin Banki ◽  
Pasquale Ferrante ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Systemic Lupus

scholarly journals Selective suppression of retroviral gp70-anti-gp70 immune complex formation by prostaglandin E1 in murine systemic lupus erythematosus.

1980 ◽  
Vol 152 (6) ◽  
pp. 1645-1658 ◽  
Author(s):  
S Izui ◽  
V E Kelley ◽  
P J McConahey ◽  
F J Dixon
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Complex ◽  
Lupus Erythematosus ◽  
Prostaglandin E1 ◽  
Systemic Lupus ◽  
Murine Systemic Lupus Erythematosus ◽  
Dna Antibodies ◽  
Total Concentrations ◽  
Immune Complex Formation

The effect of pharmacologic quantities of prostaglandin E1 (PGE) was investigated in three strains of mice (NZB X NZW, MRL/1, and BXSB) that spontaneously develop lupus-like glomerulonephritis. PGE-treatment prolonged survival and retarded the glomerular deposition of immune complex (IC) and the development of glomerulonephritis in NZB X NZW and MRL/1 mice, but did not similarly protect BXSB mice. Changes in the responsive strains correlated well with reduced amounts of circulating gp70 complexed with anti-gp70 antibodies compared with untreated controls, although total concentrations of gp70 (free and complexed) detectable in sera were similar in both groups of mice. The results strongly suggest that: (a) PGE selectively suppressed the immune response to retroviral gp70, (b) PGe had little effect on the quantity or quality of anti-DNA antibodies but did reduce the deposition of anti-DNA containing IC in the kidneys, and (c) gp70 IC appear to play an important role in the pathogenesis of glomerulonephritis in murine systemic lupus erythematosus.

Sequence Analysis of Human Endogenous Retrovirus Clone 4-1 in Systemic Lupus Erythematosus

Autoimmunity ◽  
2001 ◽  
Vol 33 (1) ◽  
pp. 15-21 ◽  
Author(s):  
Hitoshi Ogasawara ◽  
Takashi Hishikawa ◽  
Iwao Sekigawa ◽  
Hiroshi Hashimoto ◽  
Naoki Yamamoto ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Sequence Analysis ◽  
Lupus Erythematosus ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Systemic Lupus

scholarly journals DNA methylation of human endogenous retrovirus in systemic lupus erythematosus

2013 ◽  
Vol 58 (5) ◽  
pp. 241-249 ◽  
Author(s):  
Jeerawat Nakkuntod ◽  
Pattadon Sukkapan ◽  
Yingyos Avihingsanon ◽  
Apiwat Mutirangura ◽  
Nattiya Hirankarn
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dna Methylation ◽  
Lupus Erythematosus ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Systemic Lupus

scholarly journals NETs and oncologic process

2021 ◽  
Vol 15 (1) ◽  
pp. 107-116
Author(s):  
E. V. Slukhanchuk
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Neutrophil Extracellular Traps ◽  
Therapeutic Strategies ◽  
Innate Immune ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Activated Neutrophils ◽  
Autoimmune Conditions

Neutrophil Extracellular Traps (NETs) represent the networks consisting of DNA, histones, and proteins produced by activated neutrophils. Such structures have been proved to play a crucial role in inducing neutrophil innate immune response in the pathogenesis of such autoimmune conditions as systemic lupus erythematosus, rheumatoid arthritis, psoriasis, as well as in the pathogenesis of other non-infectious processes, e. g., clotting disorders, thrombosis, diabetes, atherosclerosis, vasculitis and oncology diseases. Recent studies on animal models and human pathologies have uncovered a tremendous role for NETs in tumor progression and metastasis. In this regard, NETs should be considered as pro-oncogenic substances, which further investigation will provide an opportunity to develop new therapeutic strategies.

Sign in / Sign up

Export Citation Format

Share Document