IL4 gene polymorphism and previous malaria experiences manipulate anti-Plasmodium falciparum antibody isotype profiles in complicated and uncomplicated malaria.
BACKGROUND
The IL4-590 gene polymorphism has been shown to be associated with elevated levels of anti-Plasmodium falciparum IgG antibodies and parasite intensity in the malaria protected Fulani of West Africa. This study aimed to investigate the possible impact of IL4-590C/T polymorphism on anti-P. falciparum IgG subclasses and IgE antibodies levels and the alteration of malaria severity in complicated and uncomplicated malaria patients with or without previous malaria experiences.


METHODS
Anti-P.falciparum IgG subclasses and IgE antibodies in plasma of complicated and uncomplicated malaria patients with or without previous malaria experiences were analysed using ELISA. IL4-590 polymorphisms were genotyped using RFLP-PCR. Statistical analyses of the IgG subclass levels were done by Oneway ANOVA. Genotype differences were tested by Chi-squared test.


RESULTS
The IL4-590T allele was significantly associated with anti-P. falciparum IgG3 antibody levels in patients with complicated (P = 0.031), but not with uncomplicated malaria (P = 0.622). Complicated malaria patients with previous malaria experiences carrying IL4-590TT genotype had significantly lower levels of anti-P. falciparum IgG3 (P = 0.0156), while uncomplicated malaria patients with previous malaria experiences carrying the same genotype had significantly higher levels (P = 0.0206) compared to their IL4-590 counterparts. The different anti-P. falciparum IgG1 and IgG3 levels among IL4 genotypes were observed. Complicated malaria patients with previous malaria experiences tended to have lower IgG3 levels in individuals carrying TT when compared to CT genotypes (P = 0.075). In contrast, complicated malaria patients without previous malaria experiences carrying CC genotype had significantly higher anti-P. falciparum IgG1 than those carrying either CT or TT genotypes (P = 0.004, P = 0.002, respectively).


CONCLUSIONS
The results suggest that IL4-590C or T alleles participated differently in the regulation of anti-malarial antibody isotype profiles in primary and secondary malaria infection and, therefore, could play an important role in alteration of malaria severity.
Tangteerawatana
Piyatida
P
Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand. tmskm@mahidol.ac.th.
Perlmann
Hedvig
H
Hayano
Masashi
M
Kalambaheti
Thareerat
T
Troye-Blomberg
Marita
M
Khusmith
Srisin
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000917:Antibody Formation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood* / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood* / Q000235:genetics / Q000276:immunology; D007132:Immunoglobulin Isotypes; D015847:Interleukin-4 / Q000097:blood / Q000235:genetics*; D016778:Malaria, Falciparum / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012720:Severity of Illness Index; D055815:Young Adult
D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D015847:Interleukin-4; D007073:Immunoglobulin E