BACKGROUND: According to the worldwide growing number of examined tick-borne diseases, the aim of this study was to evaluate the changes in proteomic profile of human serum induced by the development of Erythema migrans (EM), human granulocytic anaplasmosis (AP) and co-infection before/after antibiotic therapy. METHODS: A proteomics approach based on SDS-PAGE/LC-MS/MS analysis was used to determine the proteins expression and 15d-PGE2 adducts level with albumin isolated from the serum of patients and sex/age-matched healthy donors. FINDINGS: In the serum proteome of the patients with EM or/and AP, significant changes occurred in the expression of the same top 15 modified proteins
however, each protein level was modified in the different way in terms of comparing B. burgdorferi and A. phagocytophilum infections, as well as before and after therapy. In the case of co-infection, the differences in protein expression before and after therapy were significantly lower than in the monoinfection. Moreover, both EM and AP infections/co-infection significantly increased the albumin ability to create adducts with 15d-PGE2. The therapy partially reversed this property only in the case of a single infection, but this effect was not observed for therapy of co-infections. INTERPRETATION: The results demonstrate how challenging is the treatment of the tick-borne co-infections and how important is further analysis of this subject. Individual differences are also observed in each of examined in this study diseases, which makes it more difficult to develop a common biomarker for each of the tick-borne diseases.