Osteopontin and anti-osteopontin antibodies as potential biomarkers of immune activation in patients with allergic diseases: a comprehensive approach

Rationale: Osteopontin (OPN) is a pleomorphic cytokine known to influence a wide range of immune cells; allergic asthma was previously associated with high circulating OPN levels. The aim was to evaluate OPN as a possible biomarker of immune activation in allergic patients belonging to two different ethnic groups: Caucasians and South-East Asians. B. Method: Serum OPN levels were measured by ELISA test in a series of 121 Italian adult patients affected by allergic asthma, allergic rhinitis, Hymenoptera venom allergy, food allergy, allergic contact dermatitis and IgE-mediated hypersensitivity to B-lactams. 116 healthy subjects served as controls. 576 ethnic Chinese subjects were recruited at the National University of Singapore as cross-sectional cohort of an epidemiological study on the national prevalence of allergic diseases, and OPN levels were detected by Luminex and ELISA assays. C. Results: In the Italian cohort, OPN levels were significantly higher in cases compared to controls (P=0.0010 by the Mann-Whitney test). Statistically higher OPN levels were found in asthma (P=0.0269) and food allergy (P=0.046) groups in comparison to controls. No significant differences were found (P=0.597) between Singaporeans with "lifetime asthma" (i.e., subjects presenting asthma at least once in their life) and healthy controls. However, a strong gender effect was shown, in both cases (P<0.0001) and controls (P<0.0001), with males presenting higher OPN levels in comparison to females. Consequently, the mRNA expression levels of OPN gene (SPP1) were checked with illumina chips in whole blood of males and females, and no differences were found. Several experiments with Western Blots were performed to verify if possible post-transcriptional/post-translational modifications of OPN could explain these findings