Nasopharynx and mucosa associated lymphatic tissue : studies on mucosal immunity, nasopharyngeal colonization with non-encapsulated non-typable Haemophilus influenzae and local administration of immunoglobulin in the upper respiratory tract

Nasopharyngeal colonization with non-encapsulated Haemophilus influenzae (NTHI) frequently occurs in infants and in adults with common variable immunodeficiency (CVID), but is rarely found among healthy adults. In children with recurrent episodes of acute otitis media (RAOM), NTHI is more common than in healthy individuals. Protracted nasopharyngeal colonization with one and the same NTHI strain has also been found in CVID patients. Colonization is suspected to cause deeper infections, e.g. sinusitis and pneumonia.

Our purpose was to survey the maturation of immunity in the nasopharynx (I, II), to elucidate the effect of locally administrated immunoglobulin in the nasopharynx on morbidity in RAOM infants (IV) and in well-trained athletes (V) and also nasopharyngeal colonization in RAOM infants (IV) and CVID patients (Ill). We also wished to evaluate the impact of s.c. IgG replacement therapy and antibiotic treatment in CVID on the frequency of respiratory tract infections (RTI) caused by NTHI and S. pneumoniae (VI).

Specific antibody activity against S. pneumoniae was detected by ELISA, and IL-1ß, IL-6 and TNF-[alpha] by EASIA. To characterize different strains of NTHI, we used an arbitrarily primed polymerase chain reaction and pulsed field gel electrophoresis. In nasopharyngeal secretions, the level of specific antibody activity to S. pneumoniae was on the same level in healthy as in RAOM infants. It was significantly lower than in adults, indicating that local immunity in nasopharynx is not fully developed at 1-3 years of age. Levels of IL-1ß were significantly higher in healthy infants than in those with RAOM, who often lacked nasopharyngeal cytokine activity. This suggests that RAOM infants have a local defect in cytokine production. Nasal administration of IgA/IgG reduced the frequency of nasopharyngeal colonization with H. influenzae in some CVID patients, and slightly affected upper RTI in some well-trained sportsmen. The number of RAOM infants suffering badly from acute otitis media was slightly reduced (though not significantly), by local administration of IgG.

In earlier literature, the most common bacteria in the respiratory tract of CVID patients are reported to be S. pneumoniae and H. influenzae. Now that IgG replacement therapy has reduced the frequency of S. pneumoniae, NTHI is the major problem. We have found nasopharyngeal colonization with NTHI to be reduced after 9 years of s.c. IgG replacement therapy and aggressive antibiotic treatment. In one patient, however, the same NTHI strain was detected in 1989 and again in 1999.

List of scientific papers

I. Lindberg K, Freijd A, Rynnel-Dagoo B, Hammarstrom L (1993). Anti pneumococcal antibody activity in nasopharyngeal secretions in healthy adults and children. Acta Otolaryngol. 113(5): 673-678.
https://pubmed.ncbi.nlm.nih.gov/94091137

II. Lindberg K, Rynnel-Dagoo B, Sundqvist KG (1994). Cytokines in nasopharyngeal secretions; evidence for defective IL-1 beta production in children with recurrent episodes of acute otitis media. Clin Exp Immunol. 97(3): 396-402.
https://pubmed.ncbi.nlm.nih.gov/94363902

III. Lindberg K, Samuelson A, Rynnel-Dagoo B, Smith E, Hammarstrom L (1993). Nasal administration of IgA to individuals with hypogammaglobulinemia. Scand J Infect Dis. 1993; 25(3): 395-397.
https://pubmed.ncbi.nlm.nih.gov/93369558

IV. Lindberg K, Hammarstrom L, Samuelson A, Rynnel-Dagoo B (2000). Children with recurrent episodes of acute otitis media: the effect of local administration of immunoglobulin G on acute otitis media, colonization and turnover of non-encapsulated Haemophilus influenzae in the nasopharynx. Clin Otolaryngol. 25(2): 161-168.
https://pubmed.ncbi.nlm.nih.gov/20276409

V. Lindberg K, Berglund B (1996). Effect of treatment with nasal IgA on the incidence of infectious disease in world-class canoeists. Int J Sports Med. 17(3): 235-238.
https://pubmed.ncbi.nlm.nih.gov/96320801

VI. Lindberg K, Gustafson R, Samuelson A, Rynnel-Dagoo B. Impact of IgG replacement therapy and antibiotic treatment of individuals with hypogammaglobulinemia on the frequency of respiratory tract infections caused by non-encapsulated Haemophilus influenzae and Streptococcus Pneumoniae. [Submitted]