The present study shows that serum concentrations of S100A12 are significantly increased in children at onset of AOM caused by Spn or NTHi. The concentrations of S100A12 were not significantly affected by Mcat, upper respiratory viral infection, child age at onset of AOM or frequency of AOM episodes. Our study suggests that serum S100A12 may be a useful biomarker for onset of AOM caused by Spn or NTHi and for monitoring resolution after infection.
So far, reference values for S100A12 in serum specimens in children have not been reported and normal or reference serum values of S100A12 in adults are uncertain. With a monoclonal sandwich ELISA, several groups found that mean serum S100A12 levels of healthy adults ranged from 10.7 to 75.0 ng/mL (3
). However, when using other methods, like mass spectrometry, mean values of S100A12 below 10 ng/mL for healthy adults were obtained (11
). The current study showed that the mean serum concentration of S100A12 in normal healthy children was 12.1 ng/mL. With recovery, S100A12 serum levels had a mean of 13.5 ng/mL. This observation provides the first reference for future study of S100A12 in children.
Broides et al (12
) found that white blood cell (WBC) counts were higher in the MEF of patients with culture-positive AOM caused by Spn
than in those with culture-negative AOM (12
). Qvarnberg et al. (13
) also found a higher number of neutrophils in AOM caused by Spn
than in AOM cases in which no pathogens were isolated. The significant increase of S100A12 serum concentrations in children with AOM may be related to the activation, proliferation and recruitment of neutrophils and other inflammatory cells to the middle ear site.
We found that serum S100A12 value varied among otopathogens. In Spn
-induced AOM, S100A12 was elevated more than in NTHi
-induced AOM; and in Mcat-
induced AOM, no significant change of S100A12 was found. This observation may be related to the pathogen-stimulated activation of neutrophils. Previous clinical work has shown that AOM caused by Spn
is associated with significantly more symptoms and signs of inflammation than AOM caused by NTHi
). The number of WBC counted in the MEF of patients with AOM caused by Spn
has been shown to be significantly higher than the number of white blood cells found in the MEF of patients with AOM caused by NTHi
Respiratory syncytial virus, rhinovirus, influenza or parainfluenza viruses are frequently detected in the NP and sometimes in the middle ear fluid of children with AOM (6
). To assess whether the elevated serum levels of S100A12 at onset of AOM were a consequence of a viral URI, we evaluated serum levels of S100A12 in such children and in healthy, virus negative children. As expected no differences were found between the two groups, because secretion of S100A12 is an indicator of activated neutrophils, and many upper respiratory viral infections, including those caused by influenza and parainfluenza, decrease the neutrophil count (17
). The finding that serum S100A12 levels and responses were not different among different age cohorts or among NOP and OP children suggests neutrophil activation is not affected by age in the range we studied (6–33 months) or by the OP state.