Peter Gronski

Polyreactive antibodies in multidonor-derived immunoglobulin G: theory and conclusions drawn from experiments.

Multidonor-derived (md) preparations of IgG antibodies, agents of therapeutic potential, contain molecules interacting at clonal concentrations (concns) and with affinities recently estimated to cover a considerable range. Here we demonstrate that polyreactivity of the monomeric molecules represents the essential driving force of formation of the main reaction product, the IgG-dimers. This conclusion is obtained by applying the principles of the law of mass action to dimer formation by polyreactive monomeric reactants. In addition, general interrelationships involving the mean number of reactants per reactor, the experimental dimer portion (w/w) and the mean concentrations of monomers in a polyreactive and monoreactive antibody system are derived. These interrelationships, together with quantitative results obtained from simplified computational kinetic models of polyreactive antibodies, allow to estimate a remarkably high value for the mean number of reactants per reactor, exceeding 60 for the underlying IgG preparation obtained from pooled human plasma units of 5000 donors. Moreover, the potential origin and other consequences of polyreactivity are outlined.

Sera and immunoglobulins

A century ago, PASSIVE IMMUNOTHERAPY consisted of plasma preparations containing Ab of animal origin. Repeated prophylaxis and treatment with such agents was associated with severe side-effects. This was solved by continuous improvement of the process of protein purification resulting in homologous Ig preparations devoid of aggregates with Fc effector function. The main active component of these products is polyclonal IgG. Nowadays, an increasing number of monoclonal humanised or human IgG preparations with selected specificity and in different subclasses have been developed for special therapeutic purposes. With more than 100 different mAb products in different stages of clinical development, we can expect the number of licensed products to increase considerably over the next few years.