Alterations of the salivary secretory peptidome profile in children affected by type 1 diabetes

Abstract

The acidic soluble fraction of whole saliva of type 1 diabetic children was analyzed by reversed phase (RP)(1)-HPLC-ESI-MS and compared with that of sex- and age-matched control subjects. Salivary acidic proline-rich phosphoproteins (aPRP), histatins, α-defensins, salivary cystatins, statherin, proline-rich peptide P-B (P-B), beta-thymosins, S100A8 and S100A9*(S100A9* corresponds to S100A9 vairant lacking the first four amino acids), as well some naturally occurring peptides derived from salivary acidic proline-rich phosphoproteins, histatins, statherin, and P-B peptide, were detected and quantified on the basis of the extracted ion current peak area. The level of phosphorylation of salivary acidic proline-rich phosphoproteins, histatin-1 (Hst-1), statherin and S100A9* and the percentage of truncated forms of salivary acidic proline-rich phosphoproteins was also determined in the two groups. The study revealed that statherin, proline-rich peptide P-B, P-C peptide, and histatins, were significantly less concentrated in saliva of diabetic subjects than in controls, while concentration of α-defensins 1, 2 and 4 and S100A9* was higher. The low concentration of P-C peptide was paralleled by high levels of some of its fragments. On the whole, the study highlighted the severe impairment of the repertoire of peptides involved in the safeguard of the oral cavity in children who have diabetes, as well as an higher concentration of the proinflammatory mediator S100A9* with respect to healthy children.

Fig. 1.

Typical RP-HPLC-ESI profile of the acidic soluble fraction of human whole saliva of a control subject (A) and a Type 1 diabetic patient (B). Elution ranges of the principal classes of human salivary proteins/peptides are indicated. The other panels show the extracted ion current (XIC) peaks of nonphosphorylated S100A9* (C), phosphorylated S100A9* (D), nonphosphorylated oxidized S100A9* (E), phosphorylated oxidized S100A9* (F), and S100A8 (G).