FcγRIIa Polymorphism in Systemic  Lupus erythematosus

Tan, Si-Yen

doi:10.1159/000025967

Cited by 6 publications

(2 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The importance of low affinity FcγRs in the development of autoimmune diseases and defense against bacterial infections has recently been well documented (16,22,23,25,27). The consequences of polymorphisms in CD32A, particularly their different ligand binding characteristics, are being intensely investigated due to their role in certain infectious and autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of the Interaction of Human IgG Subtype Immune Complexes with Cells Expressing R and H Allelic Forms of a Low-Affinity Fcγ Receptor CD32A

Shashidharamurthy

Zhang

Amano

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

CD32A, the major phagocytic FcγR in humans, exhibits a polymorphism in the ligand binding domain. Individuals homozygous for the R allelic form of CD32A (CD32AR allele) are more susceptible to bacterial infections and autoimmune diseases as compared with H allelic CD32A (CD32AH) homozygous and CD32AR/H heterozygous individuals. To understand the mechanisms behind this differential susceptibility, we have investigated the dynamics of the interaction of these allelic forms of CD32A when they are simultaneously exposed to immune complexes (IC). Binding studies using Ig fusion proteins of CD32A alleles showed that the R allele has significantly lower binding not only to human IgG2, but also to IgG1 and IgG3 subtypes. Competition assays using purified molecules demonstrated that CD32AH-Ig outcompetes CD32AR-Ig for IC binding when both alleles simultaneously compete for the same ligand. CD32AH-Ig blocked the IC binding mediated by both the allelic forms of cell surface CD32A, whereas CD32AR-Ig blocked only CD32AR and was unable to cross-block IC binding mediated by CD32AH. Two-dimensional affinity measurements also demonstrated that CD32AR has significantly lower affinity toward all three subtypes as compared with CD32AH. Our data suggest that the lower binding of CD32AR not only to IgG2 but also to IgG1 and IgG3 might be responsible for the lack of clearance of IC leading to increased susceptibility to bacterial infections and autoimmune diseases. Our data further suggests that in humans, inflammatory cells from CD32AR/H heterozygous individuals may predominantly use the H allele to mediate Ab-coated target cell binding during phagocytosis and Ab-dependent cellular cytotoxicity, resulting in a phenotype similar to CD32AH homozygous individuals.

show abstract

Section: Discussionmentioning

confidence: 99%

Dynamics of the Interaction of Human IgG Subtype Immune Complexes with Cells Expressing R and H Allelic Forms of a Low-Affinity Fcγ Receptor CD32A

Shashidharamurthy

Zhang

Amano

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Thus it was suggested as a disease susceptibility factor for SLE, as observed in a meta-analysis that involved European, African, and Asian populations [47]. However many studies actually did not show association between polymorphism of Fc γ RIIA and SLE susceptibility in their populations [48], including Malays and Chinese in Malaysia [24]. …”

Section: Candidate Genesmentioning

confidence: 99%

Genetic Risk Factors of Systemic Lupus Erythematosus in the Malaysian Population: A Minireview

Chai

Phipps

Chua

2012

Clinical and Developmental Immunology

View full text Add to dashboard Cite

SLE is an autoimmune disease that is not uncommon in Malaysia. In contrast to Malays and Indians, the Chinese seem to be most affected. SLE is characterized by deficiency of body's immune response that leads to production of autoantibodies and failure of immune complex clearance. This minireview attempts to summarize the association of several candidate genes with risk for SLE in the Malaysian population and discuss the genetic heterogeneity that exists locally in Asians and in comparison with SLE in Caucasians. Several groups of researchers have been actively investigating genes that are associated with SLE susceptibility in the Malaysian population by screening possible reported candidate genes across the SLE patients and healthy controls. These candidate genes include MHC genes and genes encoding complement components, TNF, FcγR, T-cell receptors, and interleukins. However, most of the polymorphisms investigated in these genes did not show significant associations with susceptibility to SLE in the Malaysian scenario, except for those occurring in MHC genes and genes coding for TNF-α, IL-1β, IL-1RN, and IL-6.

show abstract