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Immune response in patients with hemorrhagic fever with renal syndrome, leptospirosis or dual infections: a comparative study

Hemorrhagic fever with renal syndrome (HFRS) and leptospirosis are acute febrile diseases most commonly affecting the kidneys. Pulmonary and liver disorders are also common. The clinical picture of HFRS can closely mimic that of unicteric leptospirosis, and vice versa. Dual infections are possible. Little is known about the pathogenesis of HFRS and even less about leptospirosis. The aim of our study was to compare the role of peripheral blood mononuclear cell (PBMC) phenotype changes, as well as the role of some cytokines and chemokines in patients with HFRS, leptospirosis or dual infections. For that purpose, we analyzed the immunophenotypic changes in the main lymphocyte populations and lymphocyte activation markers in patients with HFRS or leptospirosis, by use of whole blood two-and three-color flow cytometry. The levels of IL-10, CCL2 and CXCL8 in patient’ s sera were measured by commercial ELISA sets. HFRS and leptospirosis were serologically confirmed by ELISA IgM and IgG tests. The majority of HFRS patients expressed higher percentage of activation antigens (TCR+HLA-DR+, CD8+CD71+, CD4+CD25+, CD20+CD23+) on T- and B-lymphocytes than patients with leptospirosis. In contrast, the percentage of CD4+ and CD8+ lymphocytes simultaneously expressing both CD45RA and CD45RO markers were higher in patients with leptospirosis. The level of CCL2 and CXCL8 were significantly higher in patients with HFRS or leptospirosis than in negative controls, but there were no significant differences in the levels of both chemokines between patients with HFRS or leptospirosis. IL-10 was elevated in about 30% of patients in the early acute phase of both diseases. The level of IL-10 in patients with leptospirosis was higher than in patients with HFRS and correlated with the level of creatinine and total bilirubin. Two patients with dual infection with leptospira and virus Dobrava suggest that patients with dual infection may have stronger immune response than patients with HFRS or leptospirosis only.

HFRS; leptospirosis; cytokines; chemokines; immunophenotype

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