Exacerbation of autoantibody-mediated hemolytic anemia by viral infection

Abstract

Strong enhancement of the pathogenicity of an antierythrocyte monoclonal antibody was observed after infection of mice with lactate dehydrogenase-elevating virus. While injection of the antierythrocyte antibody alone induced only moderate anemia, concomitant infection with this virus, which is harmless in most normal mice, led to a dramatic drop in the hematocrit and to death of infected animals. In vitro and in vivo analyses showed a dramatic increase in the ability of macrophages from infected mice to phagocytose antibody-coated erythrocytes. These results indicate that viruses can trigger the onset of autoimmune disease by enhancing the pathogenicity of autoantibodies. They may explain how unrelated viruses could be implicated in the etiology of autoantibody-mediated autoimmune diseases.

FIG. 1

Effect of LDV infection on survival after antierythrocyte autoantibody inoculation. Survival was determined every day in groups of 10 BALB/c mice that received 4 mg of antierythrocyte autoantibody 34-3C or 31-9D, followed 1 day later by LDV infection. Control animals were untreated or received autoantibody 34-3C or 31-9D only.

FIG. 2

Enhancement of 34-3C antierythrocyte autoantibody-induced anemia by LDV infection. Hematocrit was measured at different times after injection of 2 mg of antierythrocyte autoantibody in groups of four or five uninfected BALB/c mice or in animals also infected with LDV. Controls were uninfected animals that received no antibody. Results are expressed as mean ± standard errors.

FIG. 3

Kinetics of LDV-induced enhancement of anemia. Hematocrit was determined 4 days after injection of 2 mg of the 34-3C antibody into BALB/c mice. LDV infection was performed at different times before or after 34-3C inoculation, as shown. Control mice were uninfected. Mice with a hematocrit of 0 were dead.

FIG. 4

In vitro erythrophagocytosis by macrophages from LDV-infected mice. Macrophages from groups of four control BALB/c mice or from four animals infected for 4 days with LDV were pooled, and their ability to phagocytose either normal red cells or erythrocytes sensitized with the 34-3C or 31-9D monoclonal antibody was measured in vitro as described in Materials and Methods.

FIG. 5

In vivo erythrophagocytosis in LDV-infected mice. Liver sections were prepared from control mice (a) and from mice 4 days after administration of 2 mg of the 34-3C antibody alone (b), LDV alone (c), or the 34-3C antibody and LDV (d). Cells that have phagocytosed large numbers of erythrocytes are shown by white arrows. The experiment was performed twice with three mice per group. Original magnification, ×460.