Immune adherence of nascent hepatitis B surface antigen-antibody complexes in vivo in humans

Upon i.v. injection into humans, pre-formed immune complexes bind complement and adhere to complement receptor type I (CR1, CD35) on erythrocytes (immune adherence). However, in most circumstances antigen and antibody react in the presence of complement; such nascent immune complexes may have properties different from pre-formed immune complexes. To define whether nascent immune complexes would also adhere to erythrocytes in vivo in humans, we studied immune complexes that formed upon i.v. injection of radiolabelled hepatitis B surface antigen (HBsAg) into immunized volunteers (eight subjects with anti-HBsAb levels ranging from undetectable to 50 U/ml.; and three control non-immune individuals). Immune complexes formed immediately in the subjects with detectable levels of specific antibody, and the clearance rate of these immune complexes correlated with the anti-HBsAb level (r = 0.78, P < 0.01). A fraction of the circulating immune complexes bound to erythrocytes in the three individuals with the highest antibody level (8-15% at 10 min). The effect of CR1 number per erythrocytes was analysed in two subjects with similar antibody levels and immune complexes clearance rates: immune adherence was higher in the subject with more CR1 per erythrocytes. The same immune complexes model studied in vitro provided similar results: a fraction of nascent immune complexes bound to human erythrocytes; this immune adherence was observed only when immune complexes formed in the presence of antibody excess, and correlated with CR1 number per erythrocytes (r = 0.99, P < 0.01). Finally, adherence of nascent HBsAg-antibody immune complexes to platelets was demonstrated in rabbits. Although immune adherence involves only a small fraction of nascent immune complexes at any given time, it may be essential for the safe disposal of large nascent immune complexes.