Nonspecific immunoglobulin M binding and chondroitin sulfate A binding are linked phenotypes of Plasmodium falciparum isolates implicated in malaria during pregnancy

Abstract

Binding of immunoglobulin M (IgM) antibodies from normal human serum to the surface of Plasmodium falciparum-infected red blood cells (iRBC) has previously been demonstrated only in parasites that form rosettes with uninfected red cells. We show that natural, nonspecific IgM but not IgG, IgA, IgD, or IgE also binds to the surface of iRBC selected for adhesion to chondroitin sulfate A (CSA), a placental receptor for parasites associated with malaria in pregnancy. The protease sensitivity of IgM-binding appears to match that of CSA binding, suggesting that the two phenotypes may be mediated by the same parasite molecule. We also show that a wide range of mouse monoclonal antibodies of the IgM class bind nonspecifically to CSA-selected iRBC, an important consideration in the interpretation of immunological assays performed on these parasite lines.

FIG. 1.

Photomicrograph of parasites of P. falciparum line Gb337CSA binding nonspecific human IgM. Immunofluorescence was detected with mouse anti-human IgM (Serotec) and Alexa Fluor 488-conjugated goat anti-mouse IgG secondary antibody (green). Parasite nuclei are stained blue with DAPI. An IgM-positive and an IgM-negative infected human erythrocyte are shown.

FIG. 2.

Abolition of IgM-binding capacity and CSA-binding capacity of parasites of P. falciparum line SD2O2CSA upon incubation with increasing concentrations of trypsin protease. Data from a representative experiment are shown. Binding to negative control (BSA) spots was less than 5 iRBC per 10 high-power fields. Two further experiments gave consistent results.