ANTIBODIES IN FALCIPARUM-MALARIA - WHAT MATTERS MOST, QUANTITY OR QUALITY

In view of the recent demonstration that antibodies that are protectiv e against Plasmodium falciparum malaria may act in collaboration with blood monocytes, we have investigated the isotype content of sera from individuals with defined clinical states of resistance or susceptibil ity to malaria. Profound differences in the distribution of each Ig su bclass and particularly in the ratio of cytophilic versus noncytophili c antibodies were found. In protected subjects, two cytophilic isotype s, IgG1 and IgG3 were found to predominate. In non-protected subjects, i.e. children and primary attack adults, three different situations w ere encountered: a) an imbalance in which IgG2, a non-cytophilic class , predominated (mostly seen in primary attacks); b) an imbalance in wh ich mostly IgM antibodies predominated (a frequent event in children) or c) less frequently, an overall low level of antimalarial antibodies . Of 33 non immune subjects studied all, except one, had one of the ab ove defects. The function of total Ig presenting such an isotype imbal ance was studied in vitro in Antibody-Dependent-Cellular-Inhibition as says. Not only did IgG from protected subjects cooperate efficiently w ith blood monocytes, whilst IgG from non-protected groups did not, but moreover the latter inhibit the in vitro effect of the former: in com petition assays whole IgG from primary attack cases with increased IgG 2 content, competed with IgG from immune adults, thus suggesting that non-protected subjects had antibodies to epitopes critical for protect ion, but that these antibodies are non functional.