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Serum levels of platelet-derived growth factor and thrombospondin-2 in patients with leptospirosis or hemorrhagic fever with renal syndrome

Hantavirus are etiological agents of hemorrhagic fever with renal syndrome (HFRS). Hantavirus disease is mainly microvascular in nature and endothelium is the predominant cell type involved. Leptospirosis is a zoonosis caused by infection with pathogenic spirochetes of the genus Leptospira. Thrombospondin-2 (TSP-2) modulates cellular interactions with extracellular matrix (including integrins). Platelet-derived growth factor (PDGF) is a hormon found to be secreted from the platelets and modulates the thrombospondin expression and secretion. The aim of the study was to define possible interaction of TSP-2 and PDGF in patients infected with hantaviruses or leptospires. We obtained sera samples from 31 HFRS patients, 11 patients with leptospirosis (including eight paired sera) and 16 controls (general population). Serology testing was done by ELISA test (HFRS) and microscopic agglutination test (MAT) -12 Leptospira interrogans serovars was used. Patients were hospitalized at the University Hospital of Infectious Diseases in Zagreb as well as in several other Infectious Diseases Departments in Croatia. Clinical and laboratory data were also collected. All sera were tested by ELISA tests for TSP-2 and PDGF-AB according to the manufacturer’s protocol (R&D Systems, Minneapolis, MN, USA). Nonparametric statistical analysis were used. Although the median values of TSP-2 in patients with HFRS or leptospirosis were higher than in control group, no significant differences were observed (p>0.05). In contrast, the levels of PDGF-AB were significantly decreased in patients with HFRS (p<0.05) or in acute sera of patients with leptospirosis (p>0.05). In paired sera of patients with leptospirosis PDGF-AB values returned to the normal levels. HFRS patients were infected mostly by Puumala virus (mild to moderate diseases). Leptospira antibodies in titres ranging from 100 to 16, 000 were found for all 12 serovars. The most commonly found serovars were Australis, Saxkoebing and Hardjo. PDGF is decreased in patient’s sera in the early, acute phase, of HFRS or leptospirosis, while at the same time, TSP-2 is increased. However, TSP-2 was decreased in the late phase of leptospirosis, while PDGF increased to normal values. The results which we obtained here are intriguing as TSP is supposed to be up-regulated by PDGF.

serum levels; thrombospondin-2; patients; leptospirosis; hemorrhagic fever; syndrome

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