Heritability and segregation analysis of immune responses to specific malaria antigens in Papua New Guinea.

Familial patterns of inheritance of immune responses to specific Plasmodium falciparum antigens were studied in 214 adults in an area of Papua New Guinea highly endemic for malaria. Preliminary variance component analysis indicated familial aggregation in both humoral and cellular immune responses against the ring-infected erythrocyte surface antigen (RESA) and the FC27 allele of the Merozoite surface antigen 2 (MSA-2). Including a term for sharing houses in the models affected only the antibody response to RESA. Segregation analysis of the antibody responses against RESA indicated inheritance via a multifactorial model and analysis of the proliferation response suggested a possible recessive major gene. The best fitting models for the immune responses against MSA-2 (FC27) postulated dominant major gene inheritance. We found no significant associations between HLA class I or II alleles and these two antigens in this population. Although there was evidence of familial aggregation of antibody responses to MSA-2 (3D7), the segregation analysis failed to identify a mode of inheritance. There was little or no heritability of either humoral or cellular immune responses against the NANP repeats of the Circumsporozoite protein (NANP), the synthetic malaria vaccine SPf66, or a preparation of MSA-2 (3D7) from which the repetitive part was deleted (MSA-2 (d3D7)). Although it is often difficult to separate genetic effects from the effects of living in the same environment, it appears that some immune responses against certain malaria antigens may be partly influenced by genetic factors.