Some Human Anti-Glycan Antibodies Lack the Ability to Activate the Complement System

Area of Science:

• Immunology
• Glycobiology
• Biochemistry

Background:

• Naturally occurring human antibodies against glycans are crucial for eliminating pathogens and abnormal cells.
• These antibodies often initiate immune responses involving the complement system.
• Aberrantly glycosylated cells, such as neoplastic cells, can be targeted by these antibodies.

Purpose of the Study:

• To investigate the complement-activating potential of human anti-glycan antibodies.
• To determine the specificities of IgM and IgG antibodies in healthy donor serum using a printed glycan array (PGA).
• To identify which bound immunoglobulins also lead to complement component C3 deposition.

Main Methods:

• Utilized a printed glycan array (PGA) with 605 glycoligands (oligo- and polysaccharides, glycopeptides).
• Examined serum from healthy donors to determine specificities of IgM and IgG anti-glycan antibodies.
• Assessed C3 deposition on the PGA to identify complement-activating antibodies.

Main Results:

• About 30% of detected anti-glycan antibodies in human serum did not activate the complement system.
• These non-activating antibodies were predominantly IgG and targeted bacterial O-antigens.
• Complement-activating antibodies recognized blood group antigens, xeno-antigens, and various bacterial polysaccharides, as expected.

Conclusions:

• A significant portion (~30%) of human anti-glycan antibodies lack complement-activating ability.
• The functional role of these prevalent, complement non-activating anti-glycan antibodies is currently unknown.
• Further research is needed to elucidate the function of these immunoglobulins that do not induce C3 deposition.