prozone

Prozone is a phenomenon in serology and immunology where very high concentrations of antibody inhibit the formation of antigen–antibody lattices required for visible precipitation or agglutination. It occurs in the zone of antibody excess, as opposed to the equivalence zone where lattice formation is optimal, and the postzone where antigen is in excess.

Mechanism: Many serologic tests rely on cross-linking multiple antigenic determinants by multivalent antibodies to produce a detectable lattice. When antibody is present in excess, individual antibodies saturate available antigen sites, preventing cross-linking between particles and thereby reducing or eliminating visible agglutination or precipitation.

Clinical relevance: The prozone effect can yield false-negative results in various antibody-detection assays, including some agglutination and precipitation tests. It has been reported in serologic testing for infectious diseases such as syphilis (in tests like VDRL and RPR) and can occur in other antibody-detection systems when antibody titers are very high, such as in hyperimmune sera or certain stages of infection.

Mitigation: If a high clinical suspicion persists despite a negative result, laboratories can test serial dilutions of the patient serum to move the reaction into the equivalence zone where lattice formation occurs. Alternative assay methods that do not depend on lattice formation can also be used. Proper interpretation often requires consideration of the possibility of a prozone effect and appropriate retesting strategies.

Related concepts include the equivalence zone and the postzone phenomenon.