Plasmodium berghei: Formation of secondary immune complexes in hyperimmune mice

Abstract

BALB/c mice infected with the lethal malaria strain Plasmodium berghei (K 173) and hyperimmune BALB/c mice which had been recovered from the infection after chloroquine therapy were used to study the formation of immune complexes in glomeruli of the kidney and in plasma, and their role in the induction of nephropathies, using electron microscopy, immunofluorescence, immunoperoxidase, and immunodiffusion techniques. Electron microscopical studies revealed comparable ultrastructural alterations in the glomeruli of infected and hyperimmune mice. Immune complexes in the glomeruli of infected mice were found to consist of immunoglobulins IgM, IgA, and IgG, complement factor, and plasmodial antigens. On the other hand, precipitating plasmodial antibodies were hardly detectable in plasma of infected mice, while plasmodial antigens were present. An increased urinary protein content was recorded in infected mice. The sera were negative in the rheumatoid factor assay. Eradication of the parasitemia by chloroquine therapy caused a gradual disappearance of plasmodial antigens from the glomerular immune complexes and from plasma within 3 weeks. The glomeruli, however, remained strongly positive for immunoglobulins and complement. Plasma and glomeruli of hyperimmune mice which had been free of parasites up to 10 weeks remained strongly positive for immunoglobulins and complement and completely negative for plasmodial antigens. No increased urinary protein content was recorded. The sera were negative for rheumatoid factor. Intravenous injections of hyperimmune serum into normal control mice and into infected athymic nude mice caused in both cases a deposition of immune complexes in the glomeruli, being negative for plasmodial antigens in the control recipients and positive in the infected nude group. These findings provide evidence that P. berghei infection in BALB/c mice caused a nontransient deposition of immune complexes of two different types: a first type in which plasmodial antigens could be demonstrated during an acute infection and a second type in which plasmodial antigens could not be demonstrated and which occurred in the plasma of recovered hyperimmune mice.