NATURAL POLYREACTIVE SECRETORY IMMUNOGLOBULIN-A AUTOANTIBODIES AS A POSSIBLE BARRIER TO INFECTION IN HUMANS

Secretory immunoglobulin A (S-IgA) was investigated in human secretion s for the presence of natural antibodies (Abs) acting as the first ''i mmune barrier'' to infection before induction or boosting of specific responses. These molecules could be the secretory counterpart of the n atural Abs in serum that were previously shown by our laboratory to be polyreactive tp autoantigens. Significant levels of S-IgA Abs to huma n actin, myosin, tubulin, and spectrin were detected in 10 saliva and 8 colostrum samples from normal subjects. Computer-assisted analysis o f immunoblots of extracts from human muscles showed these Abs to react with a large number of autoantigens. Their polyreactivity was confirm ed by cross-inhibition and by immunoblotting studies of affinity-purif ied natural Abs; assayed against a large variety of surface or secrete d antigens from Streptococcus pyogenes. The thiocyanate elution method showed that functional affinities of some natural Abs can be of the s ame order of magnitude as those of tetanus vaccine antitoxins. Moreove r, nonimmune binding of these natural Abs to the gut protein Fy (Fv-fr agment binding protein) can enhance their effector functions. This dem onstrates that human secretions contain polyreactive auto-Abs which ca n also react with pathogens. These secretory Abs of ''skeleton key'' s pecificities are possibly produced by a primordial B-l-cell-associated immune system and can be involved in a plurispecific mucosal protecti on against pathogens, irrespective of the conventional immune response .