Changes in IgA and IgG Concentrations in Nasal Secretions Prior to the Appearance of Antibody during Viral Respiratory Infection in Man

Abstract

To investigate the mechanisms of appearance of locally synthesized and plasmaderived proteins at the nasal membrane surface during upper respiratory viral infection, nasal secretions and sera from six volunteers experimentally infected with coxsackievirus A type 21 or rhinovirus type 15 were analyzed for their content of viral neutralizing antibodies, immunoglobulin and albumin. Nasal IgA increased significantly 24 hr after viral inoculation and before transudation started. In coxsackievirus infection, nasal secretion IgA concentrations continued to rise for 2 weeks to nearly twice baseline levels, whereas in rhinovirus infection a sustained rise in IgA began only after illness had subsided. Significant amounts of specific antibody did not appear in the nasal secretions during the same period. Marked transudation of albumin and IgG from plasma occurred during respiratory illness. Before illness half of the IgG in nasal secretions was synthesized locally; the remainder came from plasma as indicated by the quantity of isotopically labeled IgG which entered nasal secretions from the circulation. Viral infection inhibited local IgG synthesis; therefore, after illness subsided, nearly all IgG in nasal secretions came from the plasma. These results are consistent with the hypothesis that immunoglobulins are delivered to the nasal membrane surfaces by three different mechanisms: release of pre-formed secretory IgA during the incubation period of viral infection, transudation from the plasma before and after illness but particularly during the rhinorrhea phase of illness, and local synthesis of IgA and IgG. After illness subsides, local IgG synthesis is inhibited, but there is a marked stimulation of IgA synthesis, which, after a further period, develops specificity for the infecting virus.