The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Helga K Einarsdottir - One of the best experts on this subject based on the ideXlab platform.
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h435 containing Immunoglobulin G3 allotypes are transported efficiently across the human placenta implications for alloantibody mediated diseases of the newborn
Transfusion, 2014Co-Authors: Helga K Einarsdottir, Remco Visser, Yanli Ji, Chunyan MoAbstract:The neonatal receptor (FcRn) extends the half-life of human Immunoglobulin (Ig)G and transports it across the placenta, providing the newborn with humoral immunity. Of the four subclasses, IgG3 stands out with strong effector functions, short half-life (7 days vs. 21 days for other subclasses), and poor placental transport. We recently described how a single-amino-acid polymorphism at Position 435 in IgG3 is sufficient to explain the short half-life of R435-containing IgG3 and demonstrated that H435-IgG3 has a normal half-life of 21 days. Here, we investigated whether the R435 also explains the relatively poor placental transport of IgG3. Sera were collected from paired mothers and newborns at birth. The study included six mothers expressing R435-IgG diagnosed with fetal and neonatal alloimmune thrombocytopenia and treated with intravenous immune globulin (IVIG; containing H435-IgG3, also known as G3m16 or G3m(s,t) allotype), as well as 33 paired samples of both G3m16(-) and G3m16(+) mothers. Placental IgG transport was estimated by comparing cord and maternal concentrations of IgG subclass and G3m16 allotype. The placental transport of naturally occurring H435-IgG3 allotypes was significantly more efficient than that of other R435-IgG3 allotypes and was comparable to IgG1 transport. We demonstrate that the poor maternal-fetal transport of IgG3 is only true for most individuals of western populations where the G3m16 is not common. In G3m16(+) individuals, expressing H435-containing IgG3, IgG3 transport is similar to IgG1, which may give rise to enhanced complications in pregnancy-associated alloimmune disease in ethnic communities where this naturally occurring H435 containing IgG3 allotype is more frequent
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h435 containing Immunoglobulin G3 allotypes are transported efficiently across the human placenta implications for alloantibody mediated diseases of the newborn
Transfusion, 2014Co-Authors: Helga K Einarsdottir, Remco Visser, Yanli Ji, Chunyan MoAbstract:Background The neonatal receptor (FcRn) extends the half-life of human Immunoglobulin (Ig)G and transports it across the placenta, providing the newborn with humoral immunity. Of the four subclasses, IgG3 stands out with strong effector functions, short half-life (7 days vs. 21 days for other subclasses), and poor placental transport. We recently described how a single-amino-acid polymorphism at Position 435 in IgG3 is sufficient to explain the short half-life of R435-containing IgG3 and demonstrated that H435-IgG3 has a normal half-life of 21 days. Here, we investigated whether the R435 also explains the relatively poor placental transport of IgG3. Study Design and Methods Sera were collected from paired mothers and newborns at birth. The study included six mothers expressing R435-IgG diagnosed with fetal and neonatal alloimmune thrombocytopenia and treated with intravenous immune globulin (IVIG; containing H435-IgG3, also known as G3m16 or G3m(s,t) allotype), as well as 33 paired samples of both G3m16− and G3m16+ mothers. Placental IgG transport was estimated by comparing cord and maternal concentrations of IgG subclass and G3m16 allotype. Results The placental transport of naturally occurring H435-IgG3 allotypes was significantly more efficient than that of other R435-IgG3 allotypes and was comparable to IgG1 transport. Conclusion We demonstrate that the poor maternal–fetal transport of IgG3 is only true for most individuals of western populations where the G3m16 is not common. In G3m16+ individuals, expressing H435-containing IgG3, IgG3 transport is similar to IgG1, which may give rise to enhanced complications in pregnancy-associated alloimmune disease in ethnic communities where this naturally occurring H435 containing IgG3 allotype is more frequent.
Remco Visser - One of the best experts on this subject based on the ideXlab platform.
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hinge region o glycosylation of human Immunoglobulin G3 igG3
Molecular & Cellular Proteomics, 2015Co-Authors: Rosina Plomp, Remco Visser, Gillian Dekkers, Yoann Rombouts, Carolien A M Koeleman, Guinevere S M Kammeijer, Bas C Jansen, Theo Rispens, Paul J Hensbergen, Gestur VidarssonAbstract:Immunoglobulin G (IgG) is one of the most abundant proteins present in human serum and represents approximately three-quarters of the total serum Immunoglobulin content (1). As the main mediator of humoral immunity and an important link between the adaptive and innate immune system, IgG is a fundamental component of the immune system. IgG consists of two heavy and light chains, linked by disulfide bonds. The protein can be subdivided into the antigen-binding (Fab) and the receptor-binding (Fc) region. There are four subclasses of IgG, all of which share an overall structure homology but differ slightly in their amino acid sequence; the quantity of the subclasses in human serum is as follows: IgG1 > 2 > 3 > 4 (2). IgG3 represents ∼8% of the total amount of IgG in human serum (2), and stands out from the other IgG subclasses for a number of reasons. First of all, IgG3 contains an elongated hinge region with up to a triple repeat sequence (the actual number ranging from one to three depending on the allotype (3)), which is responsible for the increased flexibility between the Fab and the Fc part, as well as the wider and more flexible angle between the two Fab arms (4, 5). This flexibility is likely the cause of the increased affinity of IgG3, compared with the other subclasses, for divalent binding to certain types of antigens (4, 6, 7). Second, IgG3 has a higher affinity for C1q, which initiates the classical complement pathway (5, 8). The interaction between IgG3 and C1q is not due to the elongated hinge region, as demonstrated by studies showing that recombinant IgG3 with an IgG1- or IgG4-like hinge sequence exhibited even greater binding affinity for C1q than wild-type IgG3 (8–10). Third, IgG3 has a higher overall affinity for the Fcγ receptors (FcγRs), through which it can influence effector cells of the innate immune system (11). The CH2 domain and hinge region of IgG3 were shown to be instrumental in binding to the high affinity FcγRI receptor (12). Finally, IgG3 generally has a shorter half-life compared with the other IgG subclasses (1 versus 3 weeks) (2). This difference was traced back to an H435R mutation that confers a positive charge at physiological pH, resulting in a decreased binding to the neonatal Fc receptor (FcRn), which is involved in recycling IgG targeted for lysosomal degradation (13). The low-efficiency FcRn-mediated transport also gives rise to decreased levels of IgG3 in mucosal tissue and impaired transport of IgG3 across the placenta (14). These properties do not hold true for all types of IgG3 since a large number of IgG3 allotypes have been described, some of which lack the H435R substitution and have a half-life and placental transport rates similar to IgG1 (13–16). IgG3 is more polymorphic than the other IgG subclasses, as evidenced by the high number of known allotypes (16). Most of the polymorphisms reside in the CH2 or CH3 domain, but the length of the hinge region can also display a high degree of variation. Depending on the number of sequence repeats, the hinge region can vary from 27 to 83 amino acid residues between different IgG3 allotypes (3, 16, 17). An N-linked complex type glycan is highly conserved and found in the CH2 domain of all IgG subclasses and allotypes. The type of glycan present at this site has been shown to influence the effector functions of IgG (18). N-glycans that lack a core fucose cause IgG to have an enhanced proinflammatory capacity through stronger binding to FcγRIIIa and FcγRIIIb (18–20). In contrast, IgG carrying sialylated N-glycans exhibits anti-inflammatory properties, likely due to increased binding affinity to C-type lectins and/or reduced binding to FcγR (18, 21, 22). O-linked glycosylation has been reported for various Immunoglobulins. O-glycans are present on the hinge region of human IgA1 and IgD and mouse IgG2b (23–25). IgA1 contains nine potential sites for O-glycosylation (serine and threonine) in the hinge region, of which 3–5 are occupied, while IgD has been reported to carry between four and seven O-glycans (24–26). The O-glycosylation in the hinge of murine IgG2b was observed to protect against proteolytic digestion (23). Likewise, IgA1 was found to be more susceptible to degradation by Streptococci proteases after neuraminidase treatment (27). In this study, we report partial O-glycosylation of the human IgG3 hinge. We obtained both poly- and monoclonal IgG3 from various sources and performed proteolytic digestion with trypsin or proteinase K. NanoLC-reverse phase (RP)-ESI-ion trap (IT)-MS/MS was used to examine the resulting (glyco)peptides, revealing core 1-type O-glycans on multiple sites within the IgG3 hinge region.
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h435 containing Immunoglobulin G3 allotypes are transported efficiently across the human placenta implications for alloantibody mediated diseases of the newborn
Transfusion, 2014Co-Authors: Helga K Einarsdottir, Remco Visser, Yanli Ji, Chunyan MoAbstract:The neonatal receptor (FcRn) extends the half-life of human Immunoglobulin (Ig)G and transports it across the placenta, providing the newborn with humoral immunity. Of the four subclasses, IgG3 stands out with strong effector functions, short half-life (7 days vs. 21 days for other subclasses), and poor placental transport. We recently described how a single-amino-acid polymorphism at Position 435 in IgG3 is sufficient to explain the short half-life of R435-containing IgG3 and demonstrated that H435-IgG3 has a normal half-life of 21 days. Here, we investigated whether the R435 also explains the relatively poor placental transport of IgG3. Sera were collected from paired mothers and newborns at birth. The study included six mothers expressing R435-IgG diagnosed with fetal and neonatal alloimmune thrombocytopenia and treated with intravenous immune globulin (IVIG; containing H435-IgG3, also known as G3m16 or G3m(s,t) allotype), as well as 33 paired samples of both G3m16(-) and G3m16(+) mothers. Placental IgG transport was estimated by comparing cord and maternal concentrations of IgG subclass and G3m16 allotype. The placental transport of naturally occurring H435-IgG3 allotypes was significantly more efficient than that of other R435-IgG3 allotypes and was comparable to IgG1 transport. We demonstrate that the poor maternal-fetal transport of IgG3 is only true for most individuals of western populations where the G3m16 is not common. In G3m16(+) individuals, expressing H435-containing IgG3, IgG3 transport is similar to IgG1, which may give rise to enhanced complications in pregnancy-associated alloimmune disease in ethnic communities where this naturally occurring H435 containing IgG3 allotype is more frequent
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h435 containing Immunoglobulin G3 allotypes are transported efficiently across the human placenta implications for alloantibody mediated diseases of the newborn
Transfusion, 2014Co-Authors: Helga K Einarsdottir, Remco Visser, Yanli Ji, Chunyan MoAbstract:Background The neonatal receptor (FcRn) extends the half-life of human Immunoglobulin (Ig)G and transports it across the placenta, providing the newborn with humoral immunity. Of the four subclasses, IgG3 stands out with strong effector functions, short half-life (7 days vs. 21 days for other subclasses), and poor placental transport. We recently described how a single-amino-acid polymorphism at Position 435 in IgG3 is sufficient to explain the short half-life of R435-containing IgG3 and demonstrated that H435-IgG3 has a normal half-life of 21 days. Here, we investigated whether the R435 also explains the relatively poor placental transport of IgG3. Study Design and Methods Sera were collected from paired mothers and newborns at birth. The study included six mothers expressing R435-IgG diagnosed with fetal and neonatal alloimmune thrombocytopenia and treated with intravenous immune globulin (IVIG; containing H435-IgG3, also known as G3m16 or G3m(s,t) allotype), as well as 33 paired samples of both G3m16− and G3m16+ mothers. Placental IgG transport was estimated by comparing cord and maternal concentrations of IgG subclass and G3m16 allotype. Results The placental transport of naturally occurring H435-IgG3 allotypes was significantly more efficient than that of other R435-IgG3 allotypes and was comparable to IgG1 transport. Conclusion We demonstrate that the poor maternal–fetal transport of IgG3 is only true for most individuals of western populations where the G3m16 is not common. In G3m16+ individuals, expressing H435-containing IgG3, IgG3 transport is similar to IgG1, which may give rise to enhanced complications in pregnancy-associated alloimmune disease in ethnic communities where this naturally occurring H435 containing IgG3 allotype is more frequent.
Yanli Ji - One of the best experts on this subject based on the ideXlab platform.
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h435 containing Immunoglobulin G3 allotypes are transported efficiently across the human placenta implications for alloantibody mediated diseases of the newborn
Transfusion, 2014Co-Authors: Helga K Einarsdottir, Remco Visser, Yanli Ji, Chunyan MoAbstract:The neonatal receptor (FcRn) extends the half-life of human Immunoglobulin (Ig)G and transports it across the placenta, providing the newborn with humoral immunity. Of the four subclasses, IgG3 stands out with strong effector functions, short half-life (7 days vs. 21 days for other subclasses), and poor placental transport. We recently described how a single-amino-acid polymorphism at Position 435 in IgG3 is sufficient to explain the short half-life of R435-containing IgG3 and demonstrated that H435-IgG3 has a normal half-life of 21 days. Here, we investigated whether the R435 also explains the relatively poor placental transport of IgG3. Sera were collected from paired mothers and newborns at birth. The study included six mothers expressing R435-IgG diagnosed with fetal and neonatal alloimmune thrombocytopenia and treated with intravenous immune globulin (IVIG; containing H435-IgG3, also known as G3m16 or G3m(s,t) allotype), as well as 33 paired samples of both G3m16(-) and G3m16(+) mothers. Placental IgG transport was estimated by comparing cord and maternal concentrations of IgG subclass and G3m16 allotype. The placental transport of naturally occurring H435-IgG3 allotypes was significantly more efficient than that of other R435-IgG3 allotypes and was comparable to IgG1 transport. We demonstrate that the poor maternal-fetal transport of IgG3 is only true for most individuals of western populations where the G3m16 is not common. In G3m16(+) individuals, expressing H435-containing IgG3, IgG3 transport is similar to IgG1, which may give rise to enhanced complications in pregnancy-associated alloimmune disease in ethnic communities where this naturally occurring H435 containing IgG3 allotype is more frequent
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h435 containing Immunoglobulin G3 allotypes are transported efficiently across the human placenta implications for alloantibody mediated diseases of the newborn
Transfusion, 2014Co-Authors: Helga K Einarsdottir, Remco Visser, Yanli Ji, Chunyan MoAbstract:Background The neonatal receptor (FcRn) extends the half-life of human Immunoglobulin (Ig)G and transports it across the placenta, providing the newborn with humoral immunity. Of the four subclasses, IgG3 stands out with strong effector functions, short half-life (7 days vs. 21 days for other subclasses), and poor placental transport. We recently described how a single-amino-acid polymorphism at Position 435 in IgG3 is sufficient to explain the short half-life of R435-containing IgG3 and demonstrated that H435-IgG3 has a normal half-life of 21 days. Here, we investigated whether the R435 also explains the relatively poor placental transport of IgG3. Study Design and Methods Sera were collected from paired mothers and newborns at birth. The study included six mothers expressing R435-IgG diagnosed with fetal and neonatal alloimmune thrombocytopenia and treated with intravenous immune globulin (IVIG; containing H435-IgG3, also known as G3m16 or G3m(s,t) allotype), as well as 33 paired samples of both G3m16− and G3m16+ mothers. Placental IgG transport was estimated by comparing cord and maternal concentrations of IgG subclass and G3m16 allotype. Results The placental transport of naturally occurring H435-IgG3 allotypes was significantly more efficient than that of other R435-IgG3 allotypes and was comparable to IgG1 transport. Conclusion We demonstrate that the poor maternal–fetal transport of IgG3 is only true for most individuals of western populations where the G3m16 is not common. In G3m16+ individuals, expressing H435-containing IgG3, IgG3 transport is similar to IgG1, which may give rise to enhanced complications in pregnancy-associated alloimmune disease in ethnic communities where this naturally occurring H435 containing IgG3 allotype is more frequent.
P P Cleary - One of the best experts on this subject based on the ideXlab platform.
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streptococcus pyogenes type m12 protein shows selective binding to some human Immunoglobulin G3 myeloma proteins
Infection and Immunity, 1994Co-Authors: P J H Johansson, D S Retnoningrum, C Malone, R C Williams, P P ClearyAbstract:Purified, recombinant M12 protein from Streptococcus pyogenes CS24 has recently been demonstrated to bind human Immunoglobulin G3 (IgG3). The binding site for IgG has been localized to an internal peptide encoded by a PvuII fragment of the gene emm12. We have investigated the ability of an isolated recombinant M12 protein consisting of the peptide encoded by the PvuII fragment to bind various monoclonal human IgG3 myeloma proteins representing a number of both Caucasian and Oriental IgG3 Gm(allotypic) phenotypes. Of nine Caucasian IgG3 myeloma proteins, only two bound strongly to the recombinant M12 protein in enzyme-linked immunosorbent assays. The allotypic phenotypes of the reactive proteins were IgG3m(b+)(g-) and IgG3m(b-)(g+). No binding was seen for seven IgG3 myeloma proteins of Oriental origin with G3m(st+)(u-)(b+)(g-), G3m(st-)(u+)(b+)(g-), G3m(st-)(u+)(b-)(g+), and G3m(st-)(u-)(b-)(g+) phenotypes. The binding of human IgG3 to M12 protein seems to be related to features other than its Gm allotypic markers. Selective reactivity of IgG3 myeloma proteins with M12 protein may provide another way to subclassify human IgG3 molecules. The biological significance of the selective reactivity is not known.
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m12 protein from streptococcus pyogenes is a receptor for Immunoglobulin G3 and human albumin
Infection and Immunity, 1994Co-Authors: D S Retnoningrum, P P ClearyAbstract:We previously showed that M12 protein from opacity factor-negative Streptococcus pyogenes (group A streptococci) CS24 is responsible for Immunoglobulin G3 (IgG3) binding activity. Here, we report that this M protein binds human serum albumin (HSA). Deletion analysis showed that the C repeats are sufficient for binding HSA, although upstream regions may be required for optimal binding. Like protein G, IgG3 and HSA bind to independent domains in the M protein. Experiments showed that bound IgG3 did not inhibit HSA binding to the M protein. The interaction between M12 protein and HSA is specific. M12 protein does not bind chicken egg and bovine serum albumins. Alignments of C1 and C2 repeats of M12 protein to sequences at the carboxy termini of other M proteins and Ig receptors revealed highly homologous sequences in the FcRV, M5, M6, ML2.1, and M57 proteins, suggesting that all could bind HSA. As predicted from the alignment, M5 protein and M6+ streptococci bound HSA, whereas an isogenic M6- mutant did not bind HSA. Furthermore, M2 protein from an opacity factor-positive strain also bound HSA.
Chunyan Mo - One of the best experts on this subject based on the ideXlab platform.
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h435 containing Immunoglobulin G3 allotypes are transported efficiently across the human placenta implications for alloantibody mediated diseases of the newborn
Transfusion, 2014Co-Authors: Helga K Einarsdottir, Remco Visser, Yanli Ji, Chunyan MoAbstract:The neonatal receptor (FcRn) extends the half-life of human Immunoglobulin (Ig)G and transports it across the placenta, providing the newborn with humoral immunity. Of the four subclasses, IgG3 stands out with strong effector functions, short half-life (7 days vs. 21 days for other subclasses), and poor placental transport. We recently described how a single-amino-acid polymorphism at Position 435 in IgG3 is sufficient to explain the short half-life of R435-containing IgG3 and demonstrated that H435-IgG3 has a normal half-life of 21 days. Here, we investigated whether the R435 also explains the relatively poor placental transport of IgG3. Sera were collected from paired mothers and newborns at birth. The study included six mothers expressing R435-IgG diagnosed with fetal and neonatal alloimmune thrombocytopenia and treated with intravenous immune globulin (IVIG; containing H435-IgG3, also known as G3m16 or G3m(s,t) allotype), as well as 33 paired samples of both G3m16(-) and G3m16(+) mothers. Placental IgG transport was estimated by comparing cord and maternal concentrations of IgG subclass and G3m16 allotype. The placental transport of naturally occurring H435-IgG3 allotypes was significantly more efficient than that of other R435-IgG3 allotypes and was comparable to IgG1 transport. We demonstrate that the poor maternal-fetal transport of IgG3 is only true for most individuals of western populations where the G3m16 is not common. In G3m16(+) individuals, expressing H435-containing IgG3, IgG3 transport is similar to IgG1, which may give rise to enhanced complications in pregnancy-associated alloimmune disease in ethnic communities where this naturally occurring H435 containing IgG3 allotype is more frequent
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h435 containing Immunoglobulin G3 allotypes are transported efficiently across the human placenta implications for alloantibody mediated diseases of the newborn
Transfusion, 2014Co-Authors: Helga K Einarsdottir, Remco Visser, Yanli Ji, Chunyan MoAbstract:Background The neonatal receptor (FcRn) extends the half-life of human Immunoglobulin (Ig)G and transports it across the placenta, providing the newborn with humoral immunity. Of the four subclasses, IgG3 stands out with strong effector functions, short half-life (7 days vs. 21 days for other subclasses), and poor placental transport. We recently described how a single-amino-acid polymorphism at Position 435 in IgG3 is sufficient to explain the short half-life of R435-containing IgG3 and demonstrated that H435-IgG3 has a normal half-life of 21 days. Here, we investigated whether the R435 also explains the relatively poor placental transport of IgG3. Study Design and Methods Sera were collected from paired mothers and newborns at birth. The study included six mothers expressing R435-IgG diagnosed with fetal and neonatal alloimmune thrombocytopenia and treated with intravenous immune globulin (IVIG; containing H435-IgG3, also known as G3m16 or G3m(s,t) allotype), as well as 33 paired samples of both G3m16− and G3m16+ mothers. Placental IgG transport was estimated by comparing cord and maternal concentrations of IgG subclass and G3m16 allotype. Results The placental transport of naturally occurring H435-IgG3 allotypes was significantly more efficient than that of other R435-IgG3 allotypes and was comparable to IgG1 transport. Conclusion We demonstrate that the poor maternal–fetal transport of IgG3 is only true for most individuals of western populations where the G3m16 is not common. In G3m16+ individuals, expressing H435-containing IgG3, IgG3 transport is similar to IgG1, which may give rise to enhanced complications in pregnancy-associated alloimmune disease in ethnic communities where this naturally occurring H435 containing IgG3 allotype is more frequent.
