I. Kustiawan - Academia.edu (original) (raw)

Papers by I. Kustiawan

Research paper thumbnail of Inhibition of Fc gamma R-mediated phagocytosis by IVIg is independent of IgG-Fc sialylation and Fc gamma RIIb in human macrophages

Inhibition of Fc gamma R-mediated phagocytosis by IVIg is independent of IgG-Fc sialylation and Fc gamma RIIb in human macrophages

Research paper thumbnail of Inhibition of FcγR-mediated phagocytosis by IVIg is independent of IgG-Fc sialylation and FcγRIIb in human macrophages

Blood, 2014

Key Points Phagocytosis of IgG-opsonized blood cells by human macrophages is inhibited by intrave... more Key Points Phagocytosis of IgG-opsonized blood cells by human macrophages is inhibited by intravenous immunoglobulins. This inhibition is independent of IgG-Fc sialylation but improves with IgG preparations that bind FcγRs more avidly.

Research paper thumbnail of Dimeric IgG complexes from IVIg are incapable of inducing in vitro neutrophil degranulation or complement activation

PloS one, 2018

Intravenous immunoglobulin (IVIg) products contain various amounts of dimeric IgG complexes. Curr... more Intravenous immunoglobulin (IVIg) products contain various amounts of dimeric IgG complexes. Current insights into the possible biological activities of these dimers remain controversial, and both immunemodulating and immune-activating effects have been reported. Here, we analyzed the putative immune-activating effects of dimers isolated from IVIg. Dimers isolated from IVIg were purified by high-performance size-exclusion chromatography (HP-SEC) and tested for the ability to induce neutrophil degranulation in vitro. Dimers isolated from IVIg were found to be incapable of inducing in vitro neutrophil degranulation or complement activation, even at concentrations exceeding those expected to be reached upon administration in patients. These results depend on the removal of artefactual activation by using 0.1 micron filtration and the use of poloxamer to prevent adsorption of IgG onto the solid phase. The data suggest dimeric IgG found in IVIg may bind to Fc-receptors without causing ac...

Research paper thumbnail of Defects in neutrophil granule mobilization and bactericidal activity in familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) syndrome caused by STXBP2/Munc18-2 mutations

Defects in neutrophil granule mobilization and bactericidal activity in familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) syndrome caused by STXBP2/Munc18-2 mutations

Blood, 2013

Familial hemophagocytic lymphohistiocytosis (FHL) is caused by genetic defects in cytotoxic granu... more Familial hemophagocytic lymphohistiocytosis (FHL) is caused by genetic defects in cytotoxic granule components or their fusion machinery, leading to impaired natural killer cell and/or T lymphocyte degranulation and/or cytotoxicity. This may accumulate into a life-threatening condition known as macrophage activation syndrome. STXBP2, also known as MUNC18-2, has recently been identified as the disease-causing gene in FHL type 5 (FHL-5). A role for STXBP2 in neutrophils, and for neutrophils in FHL in general, has not been documented thus far. Here, we report that FHL-5 neutrophils have a profound defect in granule mobilization, resulting in inadequate bacterial killing, in particular, of gram-negative Escherichia coli, but not of Staphylococcus aureus, which rather depends on intact reduced NAD phosphate oxidase activity. This impairment of bacterial killing may contribute to the apparent susceptibility to gastrointestinal tract inflammation in patients with FHL-5.

Research paper thumbnail of A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy

A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy

Blood, 2014

Immunoglobulin G (IgG) formed during pregnancy against human platelet antigens (HPAs) of the fetu... more Immunoglobulin G (IgG) formed during pregnancy against human platelet antigens (HPAs) of the fetus mediates fetal or neonatal alloimmune thrombocytopenia (FNAIT). Because antibody titer or isotype does not strictly correlate with disease severity, we investigated by mass spectrometry variations in the glycosylation at Asn297 in the IgG Fc because the composition of this glycan can be highly variable, affecting binding to phagocyte IgG-Fc receptors (FcγR). We found markedly decreased levels of core fucosylation of anti-HPA-1a-specific IgG1 from FNAIT patients (n = 48), but not in total serum IgG1. Antibodies with a low amount of fucose displayed higher binding affinity to FcγRIIIa and FcγRIIIb, but not to FcγRIIa, compared with antibodies with a high amount of Fc fucose. Consequently, these antibodies with a low amount of Fc fucose showed enhanced phagocytosis of platelets using FcγRIIIb(+) polymorphonuclear cells or FcγRIIIa(+) monocytes as effector cells, but not with FcγRIIIa(-) monocytes. In addition, the degree of anti-HPA-1a fucosylation correlated positively with the neonatal platelet counts in FNAIT, and negatively to the clinical disease severity. In contrast to the FNAIT patients, no changes in core fucosylation were observed for anti-HLA antibodies in refractory thrombocytopenia (post platelet transfusion), indicating that the level of fucosylation may be antigen dependent and/or related to the immune milieu defined by pregnancy.

Research paper thumbnail of Inhibition of Fc gamma R-mediated phagocytosis by IVIg is independent of IgG-Fc sialylation and Fc gamma RIIb in human macrophages

Inhibition of Fc gamma R-mediated phagocytosis by IVIg is independent of IgG-Fc sialylation and Fc gamma RIIb in human macrophages

Research paper thumbnail of Inhibition of FcγR-mediated phagocytosis by IVIg is independent of IgG-Fc sialylation and FcγRIIb in human macrophages

Blood, 2014

Key Points Phagocytosis of IgG-opsonized blood cells by human macrophages is inhibited by intrave... more Key Points Phagocytosis of IgG-opsonized blood cells by human macrophages is inhibited by intravenous immunoglobulins. This inhibition is independent of IgG-Fc sialylation but improves with IgG preparations that bind FcγRs more avidly.

Research paper thumbnail of Dimeric IgG complexes from IVIg are incapable of inducing in vitro neutrophil degranulation or complement activation

PloS one, 2018

Intravenous immunoglobulin (IVIg) products contain various amounts of dimeric IgG complexes. Curr... more Intravenous immunoglobulin (IVIg) products contain various amounts of dimeric IgG complexes. Current insights into the possible biological activities of these dimers remain controversial, and both immunemodulating and immune-activating effects have been reported. Here, we analyzed the putative immune-activating effects of dimers isolated from IVIg. Dimers isolated from IVIg were purified by high-performance size-exclusion chromatography (HP-SEC) and tested for the ability to induce neutrophil degranulation in vitro. Dimers isolated from IVIg were found to be incapable of inducing in vitro neutrophil degranulation or complement activation, even at concentrations exceeding those expected to be reached upon administration in patients. These results depend on the removal of artefactual activation by using 0.1 micron filtration and the use of poloxamer to prevent adsorption of IgG onto the solid phase. The data suggest dimeric IgG found in IVIg may bind to Fc-receptors without causing ac...

Research paper thumbnail of Defects in neutrophil granule mobilization and bactericidal activity in familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) syndrome caused by STXBP2/Munc18-2 mutations

Defects in neutrophil granule mobilization and bactericidal activity in familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) syndrome caused by STXBP2/Munc18-2 mutations

Blood, 2013

Familial hemophagocytic lymphohistiocytosis (FHL) is caused by genetic defects in cytotoxic granu... more Familial hemophagocytic lymphohistiocytosis (FHL) is caused by genetic defects in cytotoxic granule components or their fusion machinery, leading to impaired natural killer cell and/or T lymphocyte degranulation and/or cytotoxicity. This may accumulate into a life-threatening condition known as macrophage activation syndrome. STXBP2, also known as MUNC18-2, has recently been identified as the disease-causing gene in FHL type 5 (FHL-5). A role for STXBP2 in neutrophils, and for neutrophils in FHL in general, has not been documented thus far. Here, we report that FHL-5 neutrophils have a profound defect in granule mobilization, resulting in inadequate bacterial killing, in particular, of gram-negative Escherichia coli, but not of Staphylococcus aureus, which rather depends on intact reduced NAD phosphate oxidase activity. This impairment of bacterial killing may contribute to the apparent susceptibility to gastrointestinal tract inflammation in patients with FHL-5.

Research paper thumbnail of A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy

A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy

Blood, 2014

Immunoglobulin G (IgG) formed during pregnancy against human platelet antigens (HPAs) of the fetu... more Immunoglobulin G (IgG) formed during pregnancy against human platelet antigens (HPAs) of the fetus mediates fetal or neonatal alloimmune thrombocytopenia (FNAIT). Because antibody titer or isotype does not strictly correlate with disease severity, we investigated by mass spectrometry variations in the glycosylation at Asn297 in the IgG Fc because the composition of this glycan can be highly variable, affecting binding to phagocyte IgG-Fc receptors (FcγR). We found markedly decreased levels of core fucosylation of anti-HPA-1a-specific IgG1 from FNAIT patients (n = 48), but not in total serum IgG1. Antibodies with a low amount of fucose displayed higher binding affinity to FcγRIIIa and FcγRIIIb, but not to FcγRIIa, compared with antibodies with a high amount of Fc fucose. Consequently, these antibodies with a low amount of Fc fucose showed enhanced phagocytosis of platelets using FcγRIIIb(+) polymorphonuclear cells or FcγRIIIa(+) monocytes as effector cells, but not with FcγRIIIa(-) monocytes. In addition, the degree of anti-HPA-1a fucosylation correlated positively with the neonatal platelet counts in FNAIT, and negatively to the clinical disease severity. In contrast to the FNAIT patients, no changes in core fucosylation were observed for anti-HLA antibodies in refractory thrombocytopenia (post platelet transfusion), indicating that the level of fucosylation may be antigen dependent and/or related to the immune milieu defined by pregnancy.