Eintrag weiter verarbeiten
Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization
Gespeichert in:
Zeitschriftentitel: | Blood |
---|---|
Personen und Körperschaften: | , , , |
In: | Blood, 74, 1989, 5, S. 1618-1626 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
American Society of Hematology
|
Schlagwörter: |
author_facet |
Scandella, D Mattingly, M de Graaf, S Fulcher, CA Scandella, D Mattingly, M de Graaf, S Fulcher, CA |
---|---|
author |
Scandella, D Mattingly, M de Graaf, S Fulcher, CA |
spellingShingle |
Scandella, D Mattingly, M de Graaf, S Fulcher, CA Blood Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization Cell Biology Hematology Immunology Biochemistry |
author_sort |
scandella, d |
spelling |
Scandella, D Mattingly, M de Graaf, S Fulcher, CA 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v74.5.1618.1618 <jats:title>Abstract</jats:title> <jats:p>Human factor VIII(FVIII) inhibitors are pathologic, circulating antibodies that inactivate FVIII. We have examined the location of epitopes on the FVIII protein for inhibitors from hemophilia A and nonhemophilic individuals. The inhibitors were of type I or type II in the kinetics of their inactivation of FVIII. A cDNA clone of human FVIII was used to express defined FVIII protein fragments in Escherichia coli for immunoblotting with inhibitor plasma. An epitope for 18 heavy-chain inhibitors was localized to the aminoterminal 18.3 Kd of the A2 domain. Two of these inhibitors also recognized an epitope located between A1 and A2 domains. Similarly, an epitope for 23 light- chain inhibitors was localized to the C2 domain. Weaker epitopes for 13 of the same inhibitors within the C1 and C2 domains were also observed. Four of the 23 inhibitors in addition bound strongly to the A3 domain. Most inhibitors (22 of 23) were neutralized in vitro only by the FVIII fragments to which they bound on immunoblots; however, one inhibitor that was neutralized by a fragment containing the A1 domain did not bind to it on immunoblots. Conversely, 3 of 3 inhibitors that bound to the A3 domain and 5 of 15 that bound to the A2 domain were not neutralized by the corresponding fragments. The epitope specificity of an inhibitor did not depend on its source or type. Our results show that FVIII inhibitors bind to limited areas within the heavy and light chains of FVIII. Some inhibitor plasmas contain additional antibodies that may not be inhibitory.</jats:p> Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization Blood |
doi_str_mv |
10.1182/blood.v74.5.1618.1618 |
facet_avail |
Online Free |
finc_class_facet |
Biologie Medizin Chemie und Pharmazie |
format |
ElectronicArticle |
fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE4Mi9ibG9vZC52NzQuNS4xNjE4LjE2MTg |
id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE4Mi9ibG9vZC52NzQuNS4xNjE4LjE2MTg |
institution |
DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 |
imprint |
American Society of Hematology, 1989 |
imprint_str_mv |
American Society of Hematology, 1989 |
issn |
0006-4971 1528-0020 |
issn_str_mv |
0006-4971 1528-0020 |
language |
English |
mega_collection |
American Society of Hematology (CrossRef) |
match_str |
scandella1989localizationofepitopesforhumanfactorviiiinhibitorantibodiesbyimmunoblottingandantibodyneutralization |
publishDateSort |
1989 |
publisher |
American Society of Hematology |
recordtype |
ai |
record_format |
ai |
series |
Blood |
source_id |
49 |
title |
Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization |
title_unstemmed |
Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization |
title_full |
Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization |
title_fullStr |
Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization |
title_full_unstemmed |
Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization |
title_short |
Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization |
title_sort |
localization of epitopes for human factor viii inhibitor antibodies by immunoblotting and antibody neutralization |
topic |
Cell Biology Hematology Immunology Biochemistry |
url |
http://dx.doi.org/10.1182/blood.v74.5.1618.1618 |
publishDate |
1989 |
physical |
1618-1626 |
description |
<jats:title>Abstract</jats:title>
<jats:p>Human factor VIII(FVIII) inhibitors are pathologic, circulating antibodies that inactivate FVIII. We have examined the location of epitopes on the FVIII protein for inhibitors from hemophilia A and nonhemophilic individuals. The inhibitors were of type I or type II in the kinetics of their inactivation of FVIII. A cDNA clone of human FVIII was used to express defined FVIII protein fragments in Escherichia coli for immunoblotting with inhibitor plasma. An epitope for 18 heavy-chain inhibitors was localized to the aminoterminal 18.3 Kd of the A2 domain. Two of these inhibitors also recognized an epitope located between A1 and A2 domains. Similarly, an epitope for 23 light- chain inhibitors was localized to the C2 domain. Weaker epitopes for 13 of the same inhibitors within the C1 and C2 domains were also observed. Four of the 23 inhibitors in addition bound strongly to the A3 domain. Most inhibitors (22 of 23) were neutralized in vitro only by the FVIII fragments to which they bound on immunoblots; however, one inhibitor that was neutralized by a fragment containing the A1 domain did not bind to it on immunoblots. Conversely, 3 of 3 inhibitors that bound to the A3 domain and 5 of 15 that bound to the A2 domain were not neutralized by the corresponding fragments. The epitope specificity of an inhibitor did not depend on its source or type. Our results show that FVIII inhibitors bind to limited areas within the heavy and light chains of FVIII. Some inhibitor plasmas contain additional antibodies that may not be inhibitory.</jats:p> |
container_issue |
5 |
container_start_page |
1618 |
container_title |
Blood |
container_volume |
74 |
format_de105 |
Article, E-Article |
format_de14 |
Article, E-Article |
format_de15 |
Article, E-Article |
format_de520 |
Article, E-Article |
format_de540 |
Article, E-Article |
format_dech1 |
Article, E-Article |
format_ded117 |
Article, E-Article |
format_degla1 |
E-Article |
format_del152 |
Buch |
format_del189 |
Article, E-Article |
format_dezi4 |
Article |
format_dezwi2 |
Article, E-Article |
format_finc |
Article, E-Article |
format_nrw |
Article, E-Article |
_version_ |
1792340803793715204 |
geogr_code |
not assigned |
last_indexed |
2024-03-01T16:09:50.089Z |
geogr_code_person |
not assigned |
openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Localization+of+epitopes+for+human+factor+VIII+inhibitor+antibodies+by+immunoblotting+and+antibody+neutralization&rft.date=1989-10-01&genre=article&issn=1528-0020&volume=74&issue=5&spage=1618&epage=1626&pages=1618-1626&jtitle=Blood&atitle=Localization+of+epitopes+for+human+factor+VIII+inhibitor+antibodies+by+immunoblotting+and+antibody+neutralization&aulast=Fulcher&aufirst=CA&rft_id=info%3Adoi%2F10.1182%2Fblood.v74.5.1618.1618&rft.language%5B0%5D=eng |
SOLR | |
_version_ | 1792340803793715204 |
author | Scandella, D, Mattingly, M, de Graaf, S, Fulcher, CA |
author_facet | Scandella, D, Mattingly, M, de Graaf, S, Fulcher, CA, Scandella, D, Mattingly, M, de Graaf, S, Fulcher, CA |
author_sort | scandella, d |
container_issue | 5 |
container_start_page | 1618 |
container_title | Blood |
container_volume | 74 |
description | <jats:title>Abstract</jats:title> <jats:p>Human factor VIII(FVIII) inhibitors are pathologic, circulating antibodies that inactivate FVIII. We have examined the location of epitopes on the FVIII protein for inhibitors from hemophilia A and nonhemophilic individuals. The inhibitors were of type I or type II in the kinetics of their inactivation of FVIII. A cDNA clone of human FVIII was used to express defined FVIII protein fragments in Escherichia coli for immunoblotting with inhibitor plasma. An epitope for 18 heavy-chain inhibitors was localized to the aminoterminal 18.3 Kd of the A2 domain. Two of these inhibitors also recognized an epitope located between A1 and A2 domains. Similarly, an epitope for 23 light- chain inhibitors was localized to the C2 domain. Weaker epitopes for 13 of the same inhibitors within the C1 and C2 domains were also observed. Four of the 23 inhibitors in addition bound strongly to the A3 domain. Most inhibitors (22 of 23) were neutralized in vitro only by the FVIII fragments to which they bound on immunoblots; however, one inhibitor that was neutralized by a fragment containing the A1 domain did not bind to it on immunoblots. Conversely, 3 of 3 inhibitors that bound to the A3 domain and 5 of 15 that bound to the A2 domain were not neutralized by the corresponding fragments. The epitope specificity of an inhibitor did not depend on its source or type. Our results show that FVIII inhibitors bind to limited areas within the heavy and light chains of FVIII. Some inhibitor plasmas contain additional antibodies that may not be inhibitory.</jats:p> |
doi_str_mv | 10.1182/blood.v74.5.1618.1618 |
facet_avail | Online, Free |
finc_class_facet | Biologie, Medizin, Chemie und Pharmazie |
format | ElectronicArticle |
format_de105 | Article, E-Article |
format_de14 | Article, E-Article |
format_de15 | Article, E-Article |
format_de520 | Article, E-Article |
format_de540 | Article, E-Article |
format_dech1 | Article, E-Article |
format_ded117 | Article, E-Article |
format_degla1 | E-Article |
format_del152 | Buch |
format_del189 | Article, E-Article |
format_dezi4 | Article |
format_dezwi2 | Article, E-Article |
format_finc | Article, E-Article |
format_nrw | Article, E-Article |
geogr_code | not assigned |
geogr_code_person | not assigned |
id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE4Mi9ibG9vZC52NzQuNS4xNjE4LjE2MTg |
imprint | American Society of Hematology, 1989 |
imprint_str_mv | American Society of Hematology, 1989 |
institution | DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1 |
issn | 0006-4971, 1528-0020 |
issn_str_mv | 0006-4971, 1528-0020 |
language | English |
last_indexed | 2024-03-01T16:09:50.089Z |
match_str | scandella1989localizationofepitopesforhumanfactorviiiinhibitorantibodiesbyimmunoblottingandantibodyneutralization |
mega_collection | American Society of Hematology (CrossRef) |
physical | 1618-1626 |
publishDate | 1989 |
publishDateSort | 1989 |
publisher | American Society of Hematology |
record_format | ai |
recordtype | ai |
series | Blood |
source_id | 49 |
spelling | Scandella, D Mattingly, M de Graaf, S Fulcher, CA 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v74.5.1618.1618 <jats:title>Abstract</jats:title> <jats:p>Human factor VIII(FVIII) inhibitors are pathologic, circulating antibodies that inactivate FVIII. We have examined the location of epitopes on the FVIII protein for inhibitors from hemophilia A and nonhemophilic individuals. The inhibitors were of type I or type II in the kinetics of their inactivation of FVIII. A cDNA clone of human FVIII was used to express defined FVIII protein fragments in Escherichia coli for immunoblotting with inhibitor plasma. An epitope for 18 heavy-chain inhibitors was localized to the aminoterminal 18.3 Kd of the A2 domain. Two of these inhibitors also recognized an epitope located between A1 and A2 domains. Similarly, an epitope for 23 light- chain inhibitors was localized to the C2 domain. Weaker epitopes for 13 of the same inhibitors within the C1 and C2 domains were also observed. Four of the 23 inhibitors in addition bound strongly to the A3 domain. Most inhibitors (22 of 23) were neutralized in vitro only by the FVIII fragments to which they bound on immunoblots; however, one inhibitor that was neutralized by a fragment containing the A1 domain did not bind to it on immunoblots. Conversely, 3 of 3 inhibitors that bound to the A3 domain and 5 of 15 that bound to the A2 domain were not neutralized by the corresponding fragments. The epitope specificity of an inhibitor did not depend on its source or type. Our results show that FVIII inhibitors bind to limited areas within the heavy and light chains of FVIII. Some inhibitor plasmas contain additional antibodies that may not be inhibitory.</jats:p> Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization Blood |
spellingShingle | Scandella, D, Mattingly, M, de Graaf, S, Fulcher, CA, Blood, Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization, Cell Biology, Hematology, Immunology, Biochemistry |
title | Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization |
title_full | Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization |
title_fullStr | Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization |
title_full_unstemmed | Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization |
title_short | Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization |
title_sort | localization of epitopes for human factor viii inhibitor antibodies by immunoblotting and antibody neutralization |
title_unstemmed | Localization of epitopes for human factor VIII inhibitor antibodies by immunoblotting and antibody neutralization |
topic | Cell Biology, Hematology, Immunology, Biochemistry |
url | http://dx.doi.org/10.1182/blood.v74.5.1618.1618 |