Association of a novel IgG3 allele with malaria in children from the Sepik region of Papua New Guinea.

BACKGROUND Susceptibility to malaria can be influenced by host genetic factors, including immune response genes. Antibodies against Plasmodium antigens are known to play an important role in protection from clinical disease. Polymorphisms in these antibodies may result in different functional properties that could provide protection from malaria. METHODS Immunoglobulin G1 (IgG1) and IgG3 alleles and IgG3 hinge region were investigated by polymerase chain reaction (PCR) and Sanger sequencing in a longitudinal cohort of children aged 1-3 years (N=203) from East Sepik region of Papua New Guinea (PNG). Linear regression was used to investigate associations between immunoglobulin alleles and Plasmodium infections. RESULTS Seventy-eight percent of the children were either heterozygous (n=82, 40%) or homozygous (n=77, 38%) for IGHG3*30 (G3m29), a novel IgG3 allele. G3m29 has a long hinge region of 4 exons. Significantly fewer Plasmodium spp. infections were observed in children with the IGHG3*30 allele compared to children without the allele (β= -1.736, 95% CI [-3.39, -0.079], p=0.038). This effect was most noticeable for Plasmodium vivax asymptomatic infections as IGHG3*30 carriers had on average one fewer infection in the 18-month follow-up period as compared to non-IGHG3*30 allele carriers (β= -1.06; 95% CI [-2.01, -0.12], p=0.028). Additionally, IGHG3*30 allele carriers had significantly lower levels of IgG to P. vivax vaccine candidate proteins compared to non-IGHG3*30 allele carriers. CONCLUSIONS The IGHG3*30 allele is highly prevalent in the East Sepik region and is associated with fewer Plasmodium spp. infections.