Agglutination

Agglutination is the clumping of insoluble or particulate antigens, such as cells or beads, in the presence of specific antibodies. The reaction occurs when antibodies cross-link antigens on neighboring particles, forming a lattice that is visible as clumping. By contrast, soluble antigens usually precipitate rather than agglutinate.

Mechanism: Immunoglobulins bind multiple epitopes; IgM is particularly efficient due to its pentameric structure, providing multiple antigen-binding sites. IgG can also mediate agglutination but is less effective. The extent of agglutination depends on the relative concentrations of antibody and antigen and the zone of equivalence where lattice networks form. Temperature, pH, ionic strength, and particle size influence whether agglutination occurs.

Types: Direct agglutination uses whole cells bearing surface antigens, as in blood typing (ABO and Rh) where antibodies cause red blood cells to clump. Indirect (passive) agglutination uses carrier particles such as latex beads coated with antigens or antibody; examples include latex agglutination tests for rapid diagnosis. Hemagglutination refers to red blood cell agglutination, especially in viral serology assays. Agglutination inhibition is used in certain competitive assays to detect small antigens or antibodies.

Applications and limitations: Agglutination is widely used in transfusion medicine, bacteriology, and clinical serology for rapid identification of antigens or antibodies. It underpins many latex agglutination tests, bacterial grouping, and some rapid point-of-care diagnostics. Limitations include false negatives from the prozone (high antibody) or postzone (high antigen) effects, and non-specific clumping. Interpretation requires appropriate controls.