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Harry R. Koene

Bio: Harry R. Koene is an academic researcher from University of Amsterdam. The author has contributed to research in topics: Medicine & Internal medicine. The author has an hindex of 12, co-authored 18 publications receiving 1424 citations.

Papers
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Journal ArticleDOI
01 Aug 1997-Blood
TL;DR: Differences in IgG binding among the three Fc gammaRIIIa-48L/R/H isoforms are a consequence of the linked, biallelic Fc Gamma receptor IIIa-158V/F polymorphism at amino-acid position 158.

779 citations

Journal ArticleDOI
01 Feb 2008-Blood
TL;DR: It is proposed that the activating FCGR2C-ORF genotype predisposes to ITP by altering the balance of activating and inhibitory FcgammaR on immune cells.

193 citations

Journal ArticleDOI
TL;DR: In this group of SLE patients, only the distribution of the alleles of the Fc gamma RIII4-158V/F polymorphism was significantly different from that in the control group, which might indicate that macrophage expression of theFc Gamma RIIIA-158F isoform is involved in the disturbed clearance of immune complexes in patients with SLE.
Abstract: Objective. To study whether the Fc gamma RIIIA-158V/F polymorphism, which affects IgG binding affinity, is a risk factor for systemic lupus erythematosus (SLE), Methods. We genotyped a group of 70 Caucasian SLE patients for all known Fc gamma R polymorphisms. Of this group, 45 patients (64%) had nephritis, In 35 patients, this diagnosis was confirmed by renal biopsy, Results, In the total group of 70 SLE patients, the frequency of the Fc gamma RIIIA-158F allele was 0.74, versus 0.57 in healthy controls (P = 0.003), The genotype distribution of the Fc gamma RIIIA-158V/F polymorphism was also significantly different from that of the control population (P = 0.004). The distribution of the other Fc gamma R polymorphisms-Fc gamma RIIA-131R/H, Fc gamma RIIIB-NA(1/2), and Fc gamma RIIIA-48L/R/H-was similar in SLE patients and controls, Conclusion. In our group of SLE patients, only the distribution of the alleles of the Fc gamma RIII4-158V/F polymorphism nas significantly different from that in the control group. This might indicate that macrophage expression of the Fc gamma RIIIA-158F isoform is involved in the disturbed clearance of immune complexes in patients with SLE.

114 citations

Journal Article
TL;DR: A donor-dependent difference in electrophoretic mobility of deglycosylated released Fc gamma RIIIa derived from NK cells and macrophages was observed and a significantly different genotype distribution was found among 12 unrelated Caucasian Fc Gamma RIIIB gene-deficient donors.
Abstract: A donor-dependent difference in electrophoretic mobility of deglycosylated released Fc gamma RIIIa derived from NK cells and macrophages was observed. We investigated whether this was based on a polymorphism of the Fc gamma RIIIA gene. Cloning and sequencing of Fc gamma RIIIa-encoding cDNA derived from an apparently heterozygous donor showed one single nucleotide substitution at position 230 (T-->G), which was responsible for a leucine (L)-->arginine (R) substitution at position 48 in the first extracellular Ig-like domain (EC1) of Fc-gamma RIIIa and caused a higher electrophoretic mobility of Fc gamma RIIIa. An allele-specific primer annealing PCR assay was developed to amplify specifically an Fc gamma RIIIA gene-derived fragment, which was digested with AciI (recognizing G230) or MnlI (recognizing T230). MnlI restriction analysis revealed the presence of a third Fc gamma RIIIa allele with a T230-->A substitution, which predicts a change of 48-leucine into 48-histidine (H). A gene frequency of 86% for the T230 (48-L) allele, 6% for G230 (48-R), and 8% for A230 (48-H) was found. A significantly different genotype distribution was found among 12 unrelated Caucasian Fc gamma RIIIB gene-deficient donors. Fc gamma RIIIa-48R and Fc gamma RIIIa-48H showed a higher binding capacity of human (h)IgG1, hIgG3, and hIgG4 compared with Fc gamma RIIIa-48L. Finally, the CD16 mAbs 1D3 and MEM154 bound more strongly and Leu11c (B73.1) bound less to the newly identified Fc gamma RIIIa isoforms.

104 citations

Journal ArticleDOI
15 Jan 1998-Blood
TL;DR: Three healthy individuals whose neutrophils reacted positively with the SH antiserum were identified and a clear gene-dosage effect on the level of expression of neutrophil FcγRIIIb was observed.

102 citations


Cited by
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Journal ArticleDOI
TL;DR: Antibody-dependent cellular cytot toxicity assays using purified peripheral blood monocytes or natural killer cells from several donors showed enhanced cytotoxicity, especially evident at lower antibody concentrations.

2,107 citations

Journal ArticleDOI
01 Feb 2002-Blood
TL;DR: This study showed an association between the FCGR3A genotype and clinical and molecular responses to rituximab, and will certainly give rise to new pharmacogenetic approaches to the management of patients with non-Hodgkin lymphomas.

2,000 citations

Journal ArticleDOI
TL;DR: IgG-polymorphisms and post-translational modification of the antibodies in the form of glycosylation, affect IgG-function will be the focus of the current review.
Abstract: Of the five immunoglobulin isotypes, Immunoglobulin G (IgG) is most abundant in human serum. The four subclasses, IgG1, IgG2, IgG3 and IgG4 which are highly conserved, differ in their constant region, particularly in their hinges and upper CH2 domains. These regions are involved in binding to both IgG-Fc receptor (FcγR) and C1q. As a result, the different subclasses have different effector functions, both in terms of triggering FcγR-expressing cells, resulting in phagocytosis or Antibody-dependent cell-mediated cytotoxicity (ADCC), and activating complement. The Fc-regions also contain a binding epitope for the neonatal Fc-receptor (FcRn), responsible for the extended half-life, placental transport, and bidirectional transport of IgG to mucosal surfaces. However, FcRn is also expressed in myeloid cells, where it participates in both phagocytosis and antigen presentation together with classical FcγR and complement. How these properties, IgG-polymorphisms and post-translational modification of the antibodies in the form of glycosylation, affect IgG-function, will be the focus of the current review.

1,834 citations

Journal ArticleDOI
TL;DR: Select IgG1 variants with improved binding to FcγRIIIA exhibited up to 100% enhancement in antibody-dependent cell cytotoxicity using human effector cells; these variants included changes at residues not found at the binding interface in the IgG/Fcγ RIIIA co-crystal structure.

1,788 citations

Patent
Leonard G. Presta1
14 Jan 2000
TL;DR: In this article, the present invention concerns polypeptides comprising a variant of the Fc region, which have altered effector function as a consequence of one or more amino acid modifications in the region thereof.
Abstract: The present invention concerns polypeptides comprising a variant Fc region. More particularly, the present invention concerns Fc region-containing polypeptides that have altered effector function as a consequence of one or more amino acid modifications in the Fc region thereof.

1,596 citations