IgG auto- and polyreactivities of normal human sera

Area of Science:

• Immunology
• Autoimmunity
• Human Serology

Background:

• Immunoglobulin G (IgG) autoreactivities in normal human sera are typically low.
• The nature and extent of IgG autoreactivities in healthy individuals remain incompletely understood.
• Previous studies have focused on specific autoantibodies, often overlooking the broader autoreactive potential of total IgG.

Purpose of the Study:

• To investigate the presence and characteristics of IgG autoreactivities in normal human sera.
• To determine the influence of serum components on the expression of IgG autoreactivities.
• To characterize the polyreactivity and autoantigen binding patterns of human IgG.

Main Methods:

• Enzyme immunoassay (EIA) and immunoblotting were used to detect IgM and IgG autoreactivities against self-antigens and organ extracts.
• Affinity chromatography using protein G-Sepharose was employed to purify IgG from normal human sera.
• Antibody inhibition assays and DNP-Sepharose chromatography were utilized to assess antibody polyreactivity and autoantigen binding.

Main Results:

• IgM autoreactivities were consistently detected in normal human sera, while IgG autoreactivities were low in whole serum but significantly increased after IgG purification.
• Purified IgG exhibited unique autoreactivity patterns for each individual, with significant binding to various self-antigens.
• A substantial fraction of purified IgG consisted of polyreactive autoantibodies, with anti-DNP antibodies showing enhanced autoreactivity.

Conclusions:

• The majority of IgG in normal human sera comprises polyreactive autoantibodies.
• IgG autoreactivities are largely masked in whole serum due to interactions with IgM and other serum components.
• These findings suggest a significant role for polyreactive autoantibodies in maintaining immune homeostasis in healthy individuals.