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Anti-malarial IgG subclasses pattern and Fc?RIIa (CD32) polymorphism among pregnancy-associated malaria in semi-immune Saudi women.

ABSTRACT: BACKGROUND: Pregnant women remain are at an increased risk of malaria with primigravidae being at the highest risk. Genetic polymorphism of the Fc receptor IIa for immunologlobulin (Ig) G (Fc?RIIa) determines IgG subclass binding. Protection against pregnancy-associated malaria (PAM) is associated with the production of IgG specific for apical membrane antigen-1 (AMA-1). The present study was undertaken to examine the relationship between specific IgG/IgG subclasses and malaria infection. The second aim of the study is to examine the association between Fc?RIIa R/H131 polymorphism in correlation with specific anti-malarial IgG antibodies of AMA-1 distribution and asymptomatic malaria infection among Saudi women living in the southern part of Saudi Arabia. METHODS: One hundred and twenty pregnant women living in an area of meso-endemic Plasmodium falciparum malaria infection were consecutively enrolled onto the study. These pregnant women were asymptomatic and attending routine antenatal clinics. The levels of plasma antibodies (IgG and subclasses AMA-1) were measured using indirect enzyme-linked immunosorbent assays (ELISA). Genotyping of Fc?RIIa-R/H131 dimorphism was performed using gene-specific polymerase chain reaction (PCR) amplification with allele-specific restriction enzyme digestion (BstU1) of the PCR product. RESULTS: A total of sixty-two (52%) pregnant women was diagnosed with asymptomatic malarial infection (ASM) compared with 58 (48%) malaria free controls (MFC). In the ASM group, there were high levels of anti-malarial IgG1 and IgG3, when compared to MFC (P value <0.001, respectively). The Fc?RIIa-R/R131 genotype and R131 were found to be statistically significantly more prevalent in the ASM group when compared to the MFC group [55% for ASM versus 12% for MFC, odds ratio (OR) 5.62, 95% confidence interval (CI)= (2.03- 15.58), P value= 0.001]. However, the H/H131 genotype showed statistically significant association with MFC [14% for ASM versus 50% for MFC, OR(0.36), 95% CI= (0.14- 0.95), P value= 0.03]. CONCLUSIONS: The study revealed that the ASM patients had higher anti-malarial IgG and IgG subclasses antibody levels when compared to the MFC. The Fc?RIIa-R/R131 genotype and R131 allele were found to be statistically prevalent in the ASM when compared to the MFC group. The individuals carrying H/H131 were consistently associated with higher levels of anti-malarial IgG subclasses.

SUBMITTER: Nasr A

PROVIDER: S-EPMC3608938 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Anti-malarial IgG subclasses pattern and FcγRIIa (CD32) polymorphism among pregnancy-associated malaria in semi-immune Saudi women.

Nasr Amre A Hamid Osama O Al-Ghamdi Abdelhamid A Allam Gamal G

Malaria journal 20130321

<h4>Background</h4>Pregnant women remain are at an increased risk of malaria with primigravidae being at the highest risk. Genetic polymorphism of the Fc receptor IIa for immunologlobulin (Ig) G (FcγRIIa) determines IgG subclass binding. Protection against pregnancy-associated malaria (PAM) is associated with the production of IgG specific for apical membrane antigen-1 (AMA-1). The present study was undertaken to examine the relationship between specific IgG/IgG subclasses and malaria infection. ...[more]

PMID: 23517907

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Project description:The Fc-glycan profile of IgG1 anti-citrullinated peptide antibodies (ACPA) in rheumatoid arthritis (RA) patients has recently been reported to be different from non-ACPA IgG1, a phenomenon which likely plays a role in RA pathogenesis. Herein we investigate the Fc-glycosylation pattern of all ACPA-IgG isotypes and simultaneously investigate in detail the IgG protein-chain sequence repertoire. IgG from serum or plasma (S/P, n = 14) and synovial fluid (SF, n = 4) from 18 ACPA-positive RA-patients was enriched using Protein G columns followed by ACPA-purification on cyclic citrullinated peptide-2 (CCP2)-coupled columns. Paired ACPA (anti-CCP2 eluted IgG) and IgG flow through (FT) fractions were analyzed by LC-MS/MS-proteomics. IgG peptides, isotypes and corresponding Fc-glycopeptides were quantified and interrogated using uni- and multivariate statistics. The Fc-glycans from the IgG4 peptide EEQFNSTYR was validated using protein A column purification. Relative to FT-IgG4, the ACPA-IgG4 Fc-glycan-profile contained lower amounts (p = 0.002) of the agalacto and asialylated core-fucosylated biantennary form (FA2) and higher content (p = 0.001) of sialylated glycans. Novel differences in the Fc-glycan-profile of ACPA-IgG1 compared to FT-IgG1 were observed in the distribution of bisected forms (n = 5, p = 0.0001, decrease) and mono-antennnary forms (n = 3, p = 0.02, increase). Our study also confirmed higher abundance of FA2 (p = 0.002) and lower abundance of afucosylated forms (n = 4, p = 0.001) in ACPA-IgG1 relative to FT-IgG1 as well as lower content of IgG2 (p = 0.0000001) and elevated content of IgG4 (p = 0.004) in ACPA compared to FT. One λ-variable peptide sequence was significantly increased in ACPA (p = 0.0001). In conclusion, the Fc-glycan profile of both ACPA-IgG1 and ACPA-IgG4 are distinct. Given that IgG1 and IgG4 have different Fc-receptor and complement binding affinities, this phenomenon likely affects ACPA effector- and immune-regulatory functions in an IgG isotype-specific manner. These findings further highlight the importance of antibody characterization in relation to functional in vivo and in vitro studies.

Dataset Information

Anti-malarial IgG subclasses pattern and Fc?RIIa (CD32) polymorphism among pregnancy-associated malaria in semi-immune Saudi women.

Publications

Anti-malarial IgG subclasses pattern and FcγRIIa (CD32) polymorphism among pregnancy-associated malaria in semi-immune Saudi women.

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