Polymorphism of the Human Fcγ Receptor II (CD32): Molecular Basis and Functional Aspects

Warmerdam, Petra A. M.; Parren, Paul W.H.I.; Vlug, A.; Aarden, Lucien A.; Winkel, Jan G. J. van de; Capel, P. J. A.

doi:10.1016/s0171-2985(11)80639-x

Cited by 25 publications

(17 citation statements)

References 22 publications

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“…To confirm that macrophage uptake of IRBCs was antibodymediated, CD16/Fc␥ II and CD32/Fc␥ III receptors on macrophages were blocked by incubation of macrophages with the specific monoclonal antibody MAb93 (as described in Materials and Methods); antibodies directed against the CD16/Fc␥ II and CD32/Fc␥ III receptors have been shown to block Fc receptor binding by immunoglobulin G (IgG) antibodies and inhibit effector functions (17,34,35). Figure 3C shows that incubation of macrophages with the anti-Fc␥ antibody MAb93 significantly inhibits the percentage of macrophages ingesting IRBCs opsonized with sera from mice vaccinated with the genomic libraries (VR1020/30K, MCP-3/30K, and CTLA4/ 30K).…”

Section: Resultsmentioning

confidence: 99%

Induction of Specific T-Cell Responses, Opsonizing Antibodies, and Protection againstPlasmodium chabaudi adamiInfection in Mice Vaccinated with Genomic Expression Libraries Expressed in Targeted and Secretory DNA Vectors

et al. 2003

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It has been proposed that a multivalent malaria vaccine is necessary to mimic the naturally acquired resistance to this disease observed in humans. A major experimental challenge is to identify the optimal components to be used in such a multivalent vaccine. Expression library immunization (ELI) is a method for screening genomes of a pathogen to identify novel combinations of vaccine sequences. Here we describe immune responses associated with, and the protective efficacy of, genomic Plasmodium chabaudi adami DS expression libraries constructed in VR1020 (secretory), monocyte chemotactic protein-3 (chemoattractant), and cytotoxic T lymphocyte antigen 4 (lymph node-targeting) DNA vaccine vectors. With splenocytes from vaccinated mice, specific T-cell responses, as well as gamma interferon and interleukin-4 production, were observed after stimulation with P. chabaudi adami-infected erythrocytes, demonstrating the specificity of genomic library vaccination for two of the three libraries constructed. Sera obtained from mice vaccinated with genomic libraries promoted the opsonization of P. chabaudi adami-infected erythrocytes by murine macrophages in vitro, further demonstrating the induction of malaria-specific immune responses following ELI. Over three vaccine trials using biolistic delivery of the three libraries, protection after lethal challenge with P. chabaudi adami DS ranged from 33 to 50%. These results show that protective epitopes or antigens are expressed within the libraries and that ELI induces responses specific to P. chabaudi adami malaria. This study further demonstrates that ELI is a suitable approach for screening the malaria genome to identify the components of multivalent vaccines.

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Section: Resultsmentioning

confidence: 99%

Induction of Specific T-Cell Responses, Opsonizing Antibodies, and Protection againstPlasmodium chabaudi adamiInfection in Mice Vaccinated with Genomic Expression Libraries Expressed in Targeted and Secretory DNA Vectors

et al. 2003

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“…There are three FcgRII genes, FcgRIIA, FcgRIIB and FcgRIIIC which all encode receptors that do not bind monomeric IgG but only bind IgG in aggregates or immune complexes [13,14]. The transcripts arising from these genes are X FcgRIIA, generates two transcripts (HR, LR) of 1´8 kb and 2´5 kb due to alternative polyadenylation sites; X FcgRIIB, generates three transcripts from alternative splicing of exons encoding either the cytoplasmic region (b1, b2) or the signal sequence (b3); X FcgRIIC, gives rise to a single 1´8 kb transcript [15]. The mature proteins generated from FcgRIIA and FcgRIIC are 95% homologous in the extracellular and transmembrane domains, and 100% identical in the cytoplasmic domain.…”

Section: Fcgriimentioning

confidence: 99%

Fcγ receptors in autoimmune diseases

Fossati

Bucknall

Edwards

2001

Eur J Clin Investigation

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Fcg-receptors (Fcg-R) recognise the Fc portion of IgG and thus form a link between humoral and cellular immunity. These receptors are expressed by a variety of immune cells, and they function in the binding of immune complexes or IgG-opsonised particles, such as microbial pathogens. The are three major types of Fcg-R, namely Fcg-RI (CD64), Fcg-RII (CD32) and Fcg-RIII (CD16), and these differ in their ability to bind IgG and complexes. There are many isoforms of these receptors and a number of recently identified polymorphisms in their structure. This review describes the structure and function of these Fcg-Rs, and highlights how gene deficiencies and polymorphisms may contribute to the pathology of human diseases.

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“…The effect of this dimorphism on the platelet response to HIA is controversial. It has been reported that platelets with the FcgRIIa-H/ H131 genotype may be responsive to HIT [10]. Yet HIT has been reported to occur more commonly, if not exclusively, in donors who show at least one histidine allele at the 131 position [11].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of heparin-induced antibodies in patients with chronic renal failure undergoing hemodialysis

Palomo

Pereira

Alarcón

et al. 2005

J. Clin. Lab. Anal.

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Heparin-induced thrombocytopenia (HIT) type II is a serious complication of heparin therapy. It presents initially as thrombocytopenia, and is associated with thrombosis in 20-50% of the cases. HIT is related to the presence of heparin-induced antibodies (HIA), which show specificity for the PF4-heparin (PF4-H) complex. The FcgammaRIIa receptor has been suggested to participate in the pathogenic mechanism of HIA. Since patients undergoing chronic hemodialysis (HD) are exposed repeatedly to heparin, we studied the prevalence of HIA and their eventual relationship with thrombocytopenia and/or thrombosis, and the possible participation of the FcgammaRIIa polymorphism. We studied 207 patients with chronic renal failure (CRF) undergoing HD. As a control we included 130 blood donors and 28 patients with CRF without HD. The HIA patients were studied with the use of a PF4-H ELISA. Additionally, in some positive cases for the previous test, a 14C- serotonin release assay (14C-SRA) was performed. The polymorphism FcgammaRIIa H/R131 was studied by polymerase chain reaction (PCR) with allele-specific primers. Thirty-seven patients (17.9%) undergoing HD presented with HIA. The majority of these antibodies were IgG, IgM, and IgA. The HIA investigated presented specificity against the PF4-H complex, but not against PF4 alone (P<0.001). Twelve out of 22 (54.5%) PF4-H antibodies were positive when tested with the 14C-SRA. The distribution of the FcgammaRIIa polymorphism in patients and healthy controls was 42.6% and 41.6% for H/H131, 41% and 48.9% for the H/R131 isoform, and 16.4% and 9.5% for the R/R131 isoform, respectively. No statistically significant difference in the FcgammaRIIa isoform distribution was found. Twenty-nine out of 156 patients (18.5%) presented thrombocytopenia, and 21/207 (12.4%) had thrombosis of the native vein arterio-venous fistula (AVF). We did not find any statistically significant between HIA and thrombocytopenia or thrombosis. An important proportion of patients with CRF undergoing HD developed HIA, but these cases were not associated with thrombocytopenia or thrombosis of AVF. The frequency of the FcgammaRIIa polymorphism did not statistically differ between HIT type II and normal controls.

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Polymorphism of the Human Fcγ Receptor II (CD32): Molecular Basis and Functional Aspects

Cited by 25 publications

References 22 publications

Induction of Specific T-Cell Responses, Opsonizing Antibodies, and Protection againstPlasmodium chabaudi adamiInfection in Mice Vaccinated with Genomic Expression Libraries Expressed in Targeted and Secretory DNA Vectors

Induction of Specific T-Cell Responses, Opsonizing Antibodies, and Protection againstPlasmodium chabaudi adamiInfection in Mice Vaccinated with Genomic Expression Libraries Expressed in Targeted and Secretory DNA Vectors

Fcγ receptors in autoimmune diseases

Prevalence of heparin-induced antibodies in patients with chronic renal failure undergoing hemodialysis

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