Fujita T, Ohi H, Endo M, Ohsawa I, Kanmatsuse K
Department of Internal Medicine II, Nihon University School of Medicine, Tokyo, 173-8610, Japan.
Clin Immunol. 1999 Jul;92(1):97-102. doi: 10.1006/clim.1999.4729.
The role of sialidase in complement activation and in development of hypocomplementemia in patients with postinfectious acute glomerulonephritis (AGN) was investigated. In sera from 17 patients with AGN and 14 healthy controls, sialidase activity and serum levels of free and total sialic acid were measured by previously established methods. Circulating sialidase activity and serum levels of free and total sialic acid and haptoglobin were increased, and the C3 level was decreased in the acute phase of AGN. There was no correlation between free sialic acid and total sialic acid, which increased in parallel with serum levels of haptoglobin, one of the acute-phase reactants. A follow-up study of these parameters in a typical case reflected this tendency and suggested that increased sialidase after infection, in addition to complement activation by the infectious substance, could play a role in development of hypocomplementemia. To clarify this mechanism, purified neuraminidase was incubated with normal human serum under various conditions. Complement breakdown products were measured in the incubation mixture by enzyme-linked immunosorbent assay using monoclonal antibodies against iC3b, Bb, and C4d neoantigens. iC3b was generated dose-dependently in the presence of neuraminidase. Further examination revealed that iC3b and Bb were generated in the incubation mixture with neuraminidase and NHS and that C4d was not detected in the same mixture. These findings indicate that neuraminidase activates the alternative complement pathway. These in vitro data, together with the former in vivo data led us to conclude that increased sialidase after infection could accelerate the complement amplification system, resulting in hypocomplementemia in the acute phase of postinfectious AGN.
