FcγRIIa (CD32) polymorphism and anti-malarial IgG subclass pattern among Fulani and sympatric ethnic groups living in eastern Sudan

Iriemenam, Nnaemeka C.; Giha, Hayder A.; Balogun, Halima A.; Anders, Robin F.; ElGhazali, Gehad; Berzins, Klavs

doi:10.1186/1475-2875-8-43

Cited by 29 publications

(35 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clinically important polymorphisms occur in FcγRIIa (R134/H134; HR/LR) and FcγRIII (V158/F158), which influence IgG binding and are known to be associated with susceptibility to Gram-negative infection (15), autoimmune diseases (10, 13, 45), and malaria (23). Furthermore, a structural understanding of the impact of the receptor polymorphisms on recognition of different IgG glycoforms or subclasses is of particular importance for the development of effective Ab-based therapies.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the FcγRIIa-LR is the only receptor that binds human IgG2 (21), which interestingly is a major IgG class in autoimmunity (11) and in resistance to Gram-negative bacterial infection (15) and severe swine flu infection (22). A higher frequency of FcγRIIa-LR homozygous genotype was found to be associated with Plasmodium falciparum malaria resistance and consistently higher levels of anti-malarial IgG2 and IgG3 serum Ab (23). …”

mentioning

confidence: 99%

See 1 more Smart Citation

Structural Basis for FcγRIIa Recognition of Human IgG and Formation of Inflammatory Signaling Complexes

Ramsland

Farrugia

Bradford

et al. 2011

The Journal of Immunology

139

166

View full text Add to dashboard Cite

The interaction of Abs with their specific FcRs is of primary importance in host immune effector systems involved in infection and inflammation, and are the target for immune evasion by pathogens. FcγRIIa is a unique and the most widespread activating FcR in humans that through avid binding of immune complexes potently triggers inflammation. Polymorphisms of FcγRIIa (high responder/low responder [HR/LR]) are linked to susceptibility to infections, autoimmune diseases, and the efficacy of therapeutic Abs. In this article, we define the three-dimensional structure of the complex between the HR (arginine, R134) allele of FcγRIIa (FcγRIIa-HR) and the Fc region of a humanized IgG1 Ab, hu3S193. The structure suggests how the HR/LR polymorphism may influence FcγRIIa interactions with different IgG subclasses and glycoforms. In addition, mutagenesis defined the basis of the epitopes detected by FcR blocking mAbs specific for FcγRIIa (IV.3), FcγRIIb (X63-21), and a pan FcγRII Ab (8.7). The epitopes detected by these Abs are distinct, but all overlap with residues defined by crystallography to contact IgG. Finally, crystal structures of LR (histidine, H134) allele of FcγRIIa and FcγRIIa-HR reveal two distinct receptor dimers that may represent quaternary states on the cell surface. A model is presented whereby a dimer of FcγRIIa-HR binds Ag–Ab complexes in an arrangement that possibly occurs on the cell membrane as part of a larger signaling assembly.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Structural Basis for FcγRIIa Recognition of Human IgG and Formation of Inflammatory Signaling Complexes

Ramsland

Farrugia

Bradford

et al. 2011

The Journal of Immunology

139

166

View full text Add to dashboard Cite

show abstract

“…FcγR I and III have a preference for IgG1 and IgG3 and low affinity for IgG2 [63]. However, FcγRIIa has a high affinity to bind IgG2 [64]. This has potential impact on the transfer of antibodies directed to different antigens, because polysaccharides are likely to elicit more IgG2 antibodies [65,66], whereas IgG1 and IgG3 subclasses are directed primarily to proteins [67,68].…”

Section: Discussionmentioning

confidence: 99%

Neonatal infections in Saudi Arabia: association with C-reactive protein, CRP -286 (C>T>A) gene polymorphism and IgG antibodies

2013

Self Cite

View full text Add to dashboard Cite

BackgroundC-reactive protein (CRP) is a nonspecific, acute-phase protein that rises in response to infectious and non-infectious inflammatory processes. Infections are the single largest cause of neonatal deaths globally.The primary aim of this study is to examine the association between CRP gene polymorphism and serum levels of CRP in correlation with early onset sepsis (EOS) infection in newborns living in Taif city, Saudi Arabia. The second aim is to examine the relationship between specific IgG/IgG subclasses and early onset sepsis (EOS) infection among these newborns.MethodsStaphylococcus aureus (S. aureus) is one of the most common organisms related to sepsis infection in the newborn at King Abdel Aziz Specialist Hospital (KAASH). This study was conducted in Taif city, at KAASH’s neonatal intensive care unit between March and August 2012. Neonates were consecutively enrolled onto the study having met our inclusion criteria (as per our research protocol).The CRP concentration level was analysed using NycoCard® CRP Single Test. CRP -286 (C>T>A) A polymorphisms were analyzed using Pyrosequencing technology for CRP genotyping. IgG subclasses were analysed in the study population using ELISA.ResultLogistic regression analyses showed that the AA and AC genotypes were negatively associated amongst EOS neonates compared to suspected neonates. The frequency of CC and CT were significantly associated with the EOS neonates compared to the suspected group. The levels of specific IgG1, IgG2 and IgG3 antibodies were significantly lower amongst EOS compared to the suspected group.ConclusionsTaken together, the CRP-286 (C>T>A) A genotype polymorphism and specific IgG antibodies isotype levels can contribute to a reduced risk of EOS. Furthermore, CRP has a potential use in detecting EOS in neonates, which may mean earlier detection and management of EOS and subsequently better clinical outcome.

show abstract

“…In particular, HBB, IL4, IL10, HLA-G, FCGR2A, G6PD, CD36 and tumor necrosis factor (TNF) have been associated with IgG or IgG subclass levels. 13,[16][17][18][19][20][21] However, there is no published genome-wide scan for IgG or IgG subclasses directed against P. falciparum antigens.…”

Section: Introductionmentioning

confidence: 98%

“…7 Furthermore, many studies evidenced the association of high levels of cytophilic IgG subclasses and reduced parasitaemia or risk of clinical malaria; [8][9][10][11] these include IgG1, IgG3 and also IgG2 for individuals carrying the H131 allelic form of FCGR2A. 12,13 In contrast, some studies revealed a potential anti-protective role of IgG4, which was associated with susceptibility to malaria, and which may block the protective effect of cytophilic IgG. 12 There is a growing body of evidence for human genetic factors controlling the level of IgG responses against P. falciparum antigens.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide significant linkage to IgG subclass responses against Plasmodium falciparum antigens on chromosomes 8p22-p21, 9q34 and 20q13

et al. 2014

View full text Add to dashboard Cite

A genome-wide scan was conducted for the levels of total immunoglobulin G (IgG) and IgG subclasses directed against Plasmodium falciparum antigens in an urban population living in Burkina Faso. Non-parametric multipoint linkage analysis provided three chromosomal regions with genome-wide significant evidence (logarithm of the odds (LOD) score >3.6), and five chromosomal regions with genome-wide suggestive evidence (LOD score >2.2). IgG3 levels were significantly linked to chromosomes 8p22-p21 and 20q13, whereas IgG4 levels were significantly linked to chromosome 9q34. In addition, we detected suggestive linkage of IgG1 levels to chromosomes 18p11-q12 and 18q12-q21, IgG4 levels to chromosomes 1p31 and 12q24 and IgG levels to chromosome 6p24-p21. Moreover, we genotyped genetic markers located within the regions of interest in a rural population living in Burkina Faso. We detected genome-wide significant and suggestive linkage results when combining the two study populations for chromosomes 1p31, 6p24-p21, 8p22-p21, 9q34, 12q24 and 20q13. Because high anti-parasite IgG3 and low anti-parasite IgG4 levels were associated with malaria resistance, the chromosomal regions linked to IgG3 and IgG4 levels are of special interest. Although the results should be confirmed in an independent population, they may provide new insights in understanding both the genetic control of IgG production and malaria resistance.

show abstract

FcγRIIa (CD32) polymorphism and anti-malarial IgG subclass pattern among Fulani and sympatric ethnic groups living in eastern Sudan

Cited by 29 publications

References 41 publications

Structural Basis for FcγRIIa Recognition of Human IgG and Formation of Inflammatory Signaling Complexes

Structural Basis for FcγRIIa Recognition of Human IgG and Formation of Inflammatory Signaling Complexes

Neonatal infections in Saudi Arabia: association with C-reactive protein, CRP -286 (C>T>A) gene polymorphism and IgG antibodies

Genome-wide significant linkage to IgG subclass responses against Plasmodium falciparum antigens on chromosomes 8p22-p21, 9q34 and 20q13

Contact Info

Product

Resources

About