Fcγ receptor IIB gene polymorphism in adult Japanese patients with primary immune thrombocytopenia

Satoh, Takashi; Miyazaki, Kôji; Shimohira, Asako; Amano, Naoki; Okazaki, Yuka; Nishimoto, Tetsuya; Akahoshi, Tohru; Munekata, Shinichi; Kanoh, Yuhsaku; Ikeda, Yasuo; Higashihara, Masaaki; Takahashi, Shinichiro; Kuwana, Masataka

doi:10.1182/blood-2013-05-501858

Cited by 16 publications

(11 citation statements)

References 9 publications

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“…observed reduced expression of FcγRIIB on splenic macrophages in patients with ITP, and an association between H. pylori infection and low FcγRIIB levels . In a Japanese study, FcγRIIBT 232 carriers were found in an increased frequency in ITP patients compared with healthy controls, and were also more likely to demonstrate an improvement in platelet count following H. pylori eradication . Together, these data suggest an interesting link between infection and autoimmunity through the regulation of FcγRIIB expression.…”

Section: Fcγriib In Autoimmunitymentioning

confidence: 81%

FcγRIIB and autoimmunity

Espéli

Smith

Clatworthy

2015

Immunological Reviews

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Autoimmune diseases are characterized by adaptive immune responses against self-antigens, including humoral responses resulting in the production of autoantibodies. Autoantibodies generate inflammation by activating complement and engaging Fcγ receptors (FcγRs). The inhibitory receptor FcγRIIB plays a central role in regulating the generation of autoantibodies and their effector functions, which include activation of innate immune cells and the cellular arm of the adaptive immune system, via effects on antigen presentation to CD4 T cells. Polymorphisms in FcγRIIB have been associated with susceptibility to autoimmunity but protection against infections in humans and mice. In the last few years, new mechanisms by which FcγRIIB controls the adaptive immune response have been described. Notably, FcγRIIB has been shown to regulate germinal center B cells and dendritic cell migration, with potential impact on the development of autoimmune diseases. Recent work has also highlighted the implication of FcγRIIB on the regulation of the innate immune system, via inhibition of Toll-like receptor- and complement receptor-mediated activation. This review will provide an update on the role of FcγRIIB in adaptive immune responses in autoimmunity, and then focus on their emerging function in innate immunity.

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Section: Fcγriib In Autoimmunitymentioning

confidence: 81%

FcγRIIB and autoimmunity

Espéli

Smith

Clatworthy

2015

Immunological Reviews

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“…For example, the FcγRIIa-H131 genotype was found to be associated with an increased production of the pro-inflammatory cytokine IL-1β by mononuclear cells, leading to inter-individual differences in the risk for acquiring periodontitis [140]. In multiple studies carried out in diverse ethnic populations, significant associations were found between FcγR polymorphisms and inter-individual differences in susceptibility, prevalence, and prognosis of diseases like systemic lupus erythematosus (SLE) [141][142][143][144], rheumatoid arthritis (RA) [145,146], immune thrombocytopenia [147], Guillain-Barré syndrome [148][149][150], myasthenia gravis [151] pediatric autoimmune neutropenia [152], IgA nephropathy [153], inflammatory myopathies [154], anti-glomerular basement membrane antibody disease [155], Kawasaki Disease [156], periodontitis [157,158], malaria [159,160], dengue [161], and sickle cell disease [162].…”

Section: Fc Gamma Receptor Expression and Polymorphismmentioning

confidence: 99%

Understanding Inter-Individual Variability in Monoclonal Antibody Disposition

Thomas

Balthasar

2019

Antibodies

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Monoclonal antibodies (mAbs) are currently the largest and most dominant class of therapeutic proteins. Inter-individual variability has been observed for several mAbs; however, an understanding of the underlying mechanisms and factors contributing to inter-subject differences in mAb disposition is still lacking. In this review, we analyze the mechanisms of antibody disposition and the putative mechanistic determinants of inter-individual variability. Results from in vitro, preclinical, and clinical studies were reviewed evaluate the role of the neonatal Fc receptor and Fc gamma receptors (expression and polymorphism), target properties (expression, shedding, turnover, internalization, heterogeneity, polymorphism), and the influence of anti-drug antibodies. Particular attention is given to the influence of co-administered drugs and disease, and to the physiological relevance of covariates identified by population pharmacokinetic modeling, as determinants of variability in mAb pharmacokinetics.

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“…There are several points worth noting about this meta‐analysis. Firstly, the investigated polymorphisms were all missense mutations, and the nucleotide substitutions caused by mutant alleles of these polymorphisms could impact the binding of Fc gamma receptors with Ig, which might subsequently lead to immune dysfunction and give rise to multiple immunological disorders including ITP . Secondly, FcγRIIa is the only class of Fc gamma receptors expressed on platelets, and engagement of this receptor on platelets by immune complexes triggers intracellular signalling events that lead to platelet activation and aggregation .…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, it is possible that functional genetic polymorphisms of Fc gamma receptors ( FCGR ) may alter the binding affinities of Fc gamma receptors and impact individual susceptibility to ITP. Recently, several studies already explored potential associations of FCGR2A H131R , FCGR2B I232T and FCGR3A F158V polymorphisms with ITP in diverse populations, with inconsistent results . Therefore, we conducted a meta‐analysis of all relevant studies to better analyse the effects of FCGR polymorphisms on individual susceptibility to ITP.…”

Section: Introductionmentioning

confidence: 99%

Associations between FCGR polymorphisms and immune thrombocytopenia: A meta‐analysis

Chen

Gao

et al. 2019

Scand J Immunol

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Several studies already explored associations between Fc gamma receptor (FCGR) polymorphisms and immune thrombocytopenia (ITP), but the results of these studies were not consistent. Consequently, we conducted a meta-analysis of relevant studies to better analyse the effects of FCGR polymorphisms on individual susceptibility to ITP. PubMed, Web of Science, Embase and CNKI were searched for eligible studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Totally 17 studies were eligible for analyses (1200 cases and 1723 controls). Significant associations with ITP were observed for FCGR3A F158V polymorphism in dominant (P < 0.0001, OR = 0.47, 95% CI 0.39-0.57), recessive (P < 0.0001, OR = 2.03, 95% CI 1.58-2.61), overdominant (P < 0.0001, OR = 1.42, 95% CI 1.19-1.69) and allele (P < 0.0001, OR = 0.58, 95% CI 0.51-0.65) models in overall analyses. But we did not observe any significant associations with ITP for FCGR2A H131R and FCGR2B I232T polymorphisms in overall analyses. Subgroup analyses by ethnicity yielded similar positive results for FCGR3A F158V polymorphism in both Asians and Caucasians. Furthermore, subgroup analyses by type of disease revealed that FCGR2A H131R polymorphism was significantly associated with childhood-onset ITP, and FCGR3A F158V polymorphism was significantly associated with both childhood-onset and adult-onset ITP. In summary, our findings suggested that FCGR2A H131R polymorphism may serve as a potential genetic biomarker of childhood-onset ITP, while FCGR3A F158V polymorphism may serve as a potential genetic biomarker of both childhood-onset and adult-onset ITP.

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Fcγ receptor IIB gene polymorphism in adult Japanese patients with primary immune thrombocytopenia

Cited by 16 publications

References 9 publications

FcγRIIB and autoimmunity

FcγRIIB and autoimmunity

Understanding Inter-Individual Variability in Monoclonal Antibody Disposition

Associations between FCGR polymorphisms and immune thrombocytopenia: A meta‐analysis

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