Immunoglobulins in nasal secretions of healthy humans: Structural integrity of secretory immunoglobulin A1 (IgA1) and occurrence of neutralizing antibodies to IgA1 proteases of nasal bacteria

Certain bacteria, including overt pathogens as well as commensals, produce immunoglobulin A1 (IgA1) proteases, By cleaving IgA1, including secretory I gA1, in the hinge region, these enzymes may interfere with the barrier func tions of mucosal IgA antibodies, as indicated by experiments in vitro. Prev ious studies have suggested that cleavage of IgA1 in nasal secretions may b e associated with the development and perpetuation of atopic disease, To cl arify the potential effect of IgA1 protease-producing bacteria in the nasal cavity, we have analyzed immunoglobulin isotypes in nasal secretions of 11 healthy humans, with a focus on IgA, and at the same time have characteriz ed and quantified IgA1 protease-producing bacteria in the nasal flora of th e subjects. Samples in the form of nasal wash were collected by using a was hing liquid that contained lithium as an internal reference, Dilution facto rs and, subsequently, concentrations in undiluted secretions could thereby be calculated. IgA, mainly in the secretory form, was found by enzyme-linke d immunosorbent assay to be the dominant isotype in all subjects, and the v ast majority of IgA (median, 91%) was of the A1 subclass, corroborating res ults of previous analyses at the level of immunoglobulin-producing cells. L evels of serum-type immunoglobulins were low, except for four subjects in w hom levels of IgG corresponded to 20 to 66% of total IgA, Cumulative levels of IgA, IgG, and IgM in undiluted secretions ranged from 260 to 2,494 (med ian, 777) mu g ml(-1). IgA1 protease-producing bacteria (Haemophilus influe nzae, Streptococcus pneumoniae, or Streptococcus mitis biovar 1) were isola ted from the nasal cavities of seven subjects at 2.1 x 10(3) to 7.2 x 10(6) CFU per ml of undiluted secretion, corresponding to 0.2 to 99.6% of the fl ora, Nevertheless, cy-chain fragments characteristic of IgA1 protease activ ity were not detected in secretions from any subject by immunoblotting. Neu tralizing antibodies to IgA1 proteases of autologous isolates were detected in secretions from five of the seven subjects but not in those from two su bjects harboring IgA1 protease-producing S. mitis biovar 1. alpha-chain fra gments different from Fc(alpha) and Fd(alpha) were detected in some samples , possibly reflecting nonspecific proteolytic activity of microbial or host origin. These results add to previous evidence for a role of secretory imm unity in the defense of the nasal mucosa but do not help identify condition s under which bacterial IgA1 proteases may interfere with this defense.