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.

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 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.

scholarly journals Acute Effects of Steroids On Immune Complex Profile of Patients with Systemic Lupus Erythematosus

1983 ◽  
Vol 26 (5) ◽  
pp. 637-644 ◽  
Author(s):  
Robert E. Boyd ◽  
Daniel A. Birchmore ◽  
Donald L. Kaiser ◽  
Alice C. Young ◽  
John S. Davis
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Complex ◽  
Lupus Erythematosus ◽  
Acute Effects ◽  
Complex Profile ◽  
Systemic Lupus

Immune Complex Deposits in Systemic Lupus Erythematosus Kidney without Histological or Functional Alterations

1975 ◽  
Vol 5 (1) ◽  
pp. 297-309 ◽  
Author(s):  
A. Cruchaud ◽  
F. Chenais ◽  
G. J. Fournié ◽  
L. Humair ◽  
P. H. Lambert ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Complex ◽  
Lupus Erythematosus ◽  
Systemic Lupus

scholarly journals Lack of relationship between serum gp70 levels and the severity of systemic lupus erythematosus in MRL/l mice.

1986 ◽  
Vol 163 (2) ◽  
pp. 458-462 ◽  
Author(s):  
J Andrews ◽  
L Hang ◽  
A N Theofilopoulos ◽  
F J Dixon
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Complex ◽  
Lupus Erythematosus ◽  
Observable Effect ◽  
Systemic Lupus ◽  
Congenic Lines

In the MRL/l mouse, gp70 apparently plays a role as an autoantigen in the development of SLE. However, while gp70 may be an important pathogenetic element, it is not essential to MRL SLE, since elimination of most of the serum gp70 and virtually all of the immune complex gp70 from MRL/l-low gp70 congenic lines had no observable effect on the course or nature of the disease. Thus, while gp70 in the MRL/l mouse appears to be a convenient autoantigenic target when present in significant levels, in its absence the host appears capable of directing its aberrant immunologic responsiveness elsewhere with undiminished pathogenicity.

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