EndoS reduces the pathogenicity of anti-mCOL7 IgG through reduced binding of immune complexes to neutrophils

Area of Science:

• Immunology
• Autoimmune Diseases
• Glycoscience

Background:

• Autoimmune diseases like epidermolysis bullosa acquisita (EBA) involve pathogenic autoantibodies.
• Pathogen-derived enzymes, such as Endo-β-N-acetylglucosaminidase (EndoS), can modulate immune responses.
• EndoS is recognized as a potent immunomodulatory molecule in autoimmune conditions.

Purpose of the Study:

• To investigate the mechanism by which EndoS treatment mitigates the pathogenicity of rabbit anti-mCOL7 IgG in experimental EBA models.
• To elucidate how EndoS influences immune complex (IC) interactions with neutrophils.

Main Methods:

• Utilized experimental models of epidermolysis bullosa acquisita (EBA).
• Administered EndoS treatment to rabbit anti-mCOL7 IgG.
• Assessed antibody-antigen binding and IC-mediated neutrophil activation.
• Investigated the impact of EndoS on IC binding to Fcγ receptors (FcγR) on neutrophils.

Main Results:

• EndoS treatment did not affect the binding affinity of anti-mCOL7 IgG to its target antigen (mCOL7).
• EndoS significantly reduced immune complex (IC)-mediated neutrophil activation.
• The reduction in neutrophil activation was attributed to EndoS impairing the binding of ICs to Fcγ receptors on neutrophils.

Conclusions:

• EndoS exerts its immunomodulatory effect in EBA by specifically inhibiting IC-FcγR interactions on neutrophils, rather than affecting antibody-antigen binding.
• This newly identified mechanism provides a basis for developing novel therapeutic strategies targeting EndoS for EBA and potentially other autoimmune diseases.
• Targeting EndoS offers a promising avenue for managing autoimmune conditions driven by immune complex deposition and neutrophil activation.