ImmunologyTier 1Medical Sciences concept

Antibody affinity vs avidity - definitions (IgM vs IgG)

Core concept

Affinity = binding strength of a single antigen-binding site to a single epitope
Avidity = overall binding strength of an antibody for antigen, accounting for all binding sites acting together (cumulative effect of multiple low-affinity interactions)
IgM: pentameric, 10 binding sites, individually low affinity but high avidity overall -- efficient at binding multivalent antigens (e.g. bacterial surfaces) and activating complement even early in a response

IgG: monomeric (2 binding sites), affinity increases over time via somatic hypermutation and affinity maturation in the germinal centre -- high affinity, lower avidity than IgM per molecule but compensated by higher serum concentration and longer persistence
Avidity testing distinguishes recent from past infection: early antibody response = low avidity; antibody from a past/resolved infection = high avidity (has undergone maturation)
Trap: assuming "high antibody titre" means "high affinity/avidity" -- titre measures quantity, avidity measures binding quality/maturity, and the two are independent

Low-avidity IgG in a pregnant patient with a positive IgG (e.g. toxoplasma, CMV, rubella) suggests recent infection (higher risk of congenital transmission if in early pregnancy) -- avidity testing helps date the infection when IgM is unreliable or persistent
High-avidity IgG in the same scenario suggests infection occurred more than ~3-4 months ago, reducing concern about an acute event during the current pregnancy
This is the practical exam application: avidity testing timing/interpretation in antenatal infection screening, not just the definitional distinction

Directly underlies B-cell affinity maturation and somatic hypermutation (separate note) -- the germinal centre process that raises IgG affinity over the course of an immune response
IgM's high avidity/low individual affinity explains its efficiency as the first responder and potent complement activator in acute haemolytic transfusion reactions (ABO antibodies are IgM)
Same maturation principle underlies why vaccine booster doses improve antibody quality (avidity), not just quantity (titre)

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