Complement activation in nephropathia epidemica caused by Puumala hantavirus

Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome caused by Puumala hantavirus. There is considerable variability in the clinical severity of NE. Its pathogenesis is largely unknown and data on complement activation in NE are scant. We sought here to establish how the complement system behaves during NE and whether the variation in the clinical outcome is related to the activation of complement.

The complement component levels and complement activation products and the clinical course of 25 hospital-treated acutely ill NE patients were studied.

Complement activation was observed in 23 patients. In 10 patients the complement system was activated mainly through the alternative route, in 6 mainly through the classical route and in 5 through both the alternative and the classical route. An elevated soluble terminal complex SC5b-9 was the most sensitive indicator of complement activation (17 out of 25 patients). Two patients had only an elevated SC5b-9 value and 2 had no complement activation. The C4d/C4 maximal ratio was significantly higher in patients with clinically severe NE compared to the mild or moderate disease groups.

Our results show that complement activation is common in NE. Although both pathways are usually activated, the classical pathway activation by immune complexes or directly by viral components is associated with a severe clinical course of NE.