RIFIN proteins belong to the largest Plasmodium falciparum multicopy family of 
variant surface antigens (VSA) expressed by infected erythrocytes. VSA 
antibodies have been shown to be associated with protection against malaria. 
Here, antibody subclass responses to a recombinant RIFIN protein (RIF-29) in 116 
Ghanaian children were determined by ELISA to investigate the relationship 
between severe malaria and anti-RIF-29 antibodies. The study group was composed 
of 23 children diagnosed exclusively for cerebral malaria and 35 children who 
had non-cerebral severe malaria. The remaining 58 individuals were age-, gender- 
and area-matched asymptomatic controls. The finding that IgG1 and IgG3 responses 
predominated in severe malaria patients compared to matched controls suggests 
that these antibodies are not protective, but are most probably induced by a 
current infection, an observation substantiated by the equally high reactivity 
to both recombinant RIF-29 protein and to P. falciparum crude lysate proteins. 
The exclusive detection of IgG2 and IgG4 antibodies to RIF-29 protein only in 
cerebral malaria children brings to mind the possibility that these antibodies 
are pathogenic. This is a new finding that may go some way towards explaining 
why these children are at risk of developing the life-threatening form of 
cerebral malaria.