Modulation of immunoglobulin G oligomerization by variable domain glycans: A mechanism to regulate complement activation.

ABSTRACT: Immunoglobulin G (IgG) is a glycoprotein harboring conserved fragment crystallizable domain glycans, but it can also express variable domain glycans (VDGs). Elevated levels of VDGs are a hallmark of the autoantibodies most specific to rheumatoid arthritis and are also associated with other autoimmune diseases. Nonetheless, the effect of VDGs on IgG function remains poorly understood. This study investigates the impact of VDGs on the ability of antibodies to activate the complement system, a key immune effector mechanism. We demonstrate that VDGs on IgG inhibit the initiation of the classical complement pathway, as evidenced by complement activation assays with IgG displaying varying degrees of VDGs. Structure-function analyses show that VDGs reduce classical complement activation by impedi

SUBMITTER: Biersteker R 

PROVIDER: S-EPMC12305304 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature