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 Gui nea highly endemic for malaria. Preliminary variance component analysis ind icated familial aggregation in both humoral and cellular immune responses a gainst the ring-infected erythrocyte surface antigen (RESA) and the FC27 al lele of the Merozoite surface antigen 2 (MSA-2). Including a term for shari ng houses in the models affected only the antibody response to RESA. Segreg ation analysis of the antibody responses against RESA indicated inheritance via a multifactorial model and analysis of the proliferation response sugg ested a possible recessive major gene. The best fitting models for the immu ne responses against MSA-2 (FC27) postulated dominant major gene inheritanc e. We found no significant associations between HLA class I or II alleles a nd these two antigens in this population. Although there was evidence of fa milial aggregation of antibody responses to MSA-2 (3D7), the segregation an alysis failed to identify a mode of inheritance. There was little or no her itability of either humoral or cellular immune responses against the NANP r epeats of the Circumsporozoite protein (NANP), the synthetic malaria vaccin e 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 tha t some immune responses against certain malaria antigens may be partly infl uenced by genetic factors. Genet. Epidemiol. 17:16-34, 1999. (C) 1999 Wiley -Liss, Inc.