Epitope specificity and isotype of monoclonal anti-D antibodies dictate their ability to inhibit phagocytosis of opsonized platelets
(2007) In Blood 110(4). p.61-1359- Abstract
Rh immune globulin (WinRho SDF; Cangene, Mississauga, ON, Canada) is an effective treatment for autoimmune thrombocytopenic purpura; however, maintaining a sustained supply for its use in autoimmune thrombocytopenic purpura and its primary indication, hemolytic disease of the newborn, makes the development of alternative reagents desirable. We compared Rh immune globulin and 6 human monoclonal anti-D antibodies (MoAnti-D) with differing isotypes and specificities for their ability to opsonize erythrocytes and inhibit platelet phagocytosis in an in vitro assay. Results demonstrated that opsonization of erythrocytes with Rh immune globulin significantly (P < .001) reduced phagocytosis of fluorescently labeled opsonized platelets in an... (More)
Rh immune globulin (WinRho SDF; Cangene, Mississauga, ON, Canada) is an effective treatment for autoimmune thrombocytopenic purpura; however, maintaining a sustained supply for its use in autoimmune thrombocytopenic purpura and its primary indication, hemolytic disease of the newborn, makes the development of alternative reagents desirable. We compared Rh immune globulin and 6 human monoclonal anti-D antibodies (MoAnti-D) with differing isotypes and specificities for their ability to opsonize erythrocytes and inhibit platelet phagocytosis in an in vitro assay. Results demonstrated that opsonization of erythrocytes with Rh immune globulin significantly (P < .001) reduced phagocytosis of fluorescently labeled opsonized platelets in an Fc-dependent manner. Of the MoAnti-D that shared specificity but differed in isotype, only IgG3 antibodies could significantly (P < .001) inhibit platelet phagocytosis. In contrast, 2 MoAnti-D shared isotypes and differed in specificity; however, only one could significantly (P < .001) inhibit platelet phagocytosis. The results suggest that MoAnti-D epitope specificity and isotypes are critical requirements for optimal inhibition of opsonized platelet phagocytosis.
(Less)
- author
- Kjaersgaard, Mimi ; Aslam, Rukhsana ; Kim, Michael ; Speck, Edwin R ; Freedman, John ; Stewart, Donald I H ; Wiersma, Erik J and Semple, John W LU
- publishing date
- 2007-08-15
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Antibodies, Monoclonal/immunology, Antigens, Human Platelet/immunology, Autoantibodies/immunology, Blood Platelets/immunology, Epitopes/immunology, Humans, Immunoglobulin Isotypes, Opsonin Proteins, Phagocytosis, Purpura, Thrombocytopenic, Idiopathic/immunology, Rh Isoimmunization, Rho(D) Immune Globulin/immunology
- in
- Blood
- volume
- 110
- issue
- 4
- pages
- 61 - 1359
- publisher
- American Society of Hematology
- external identifiers
-
- pmid:17456719
- scopus:34548048157
- ISSN
- 0006-4971
- DOI
- 10.1182/blood-2007-03-079848
- language
- English
- LU publication?
- no
- id
- 68c1c1d0-95d5-4ed6-a779-15df84180cc6
- date added to LUP
- 2022-11-09 15:24:09
- date last changed
- 2024-10-03 00:56:34
@article{68c1c1d0-95d5-4ed6-a779-15df84180cc6, abstract = {{<p>Rh immune globulin (WinRho SDF; Cangene, Mississauga, ON, Canada) is an effective treatment for autoimmune thrombocytopenic purpura; however, maintaining a sustained supply for its use in autoimmune thrombocytopenic purpura and its primary indication, hemolytic disease of the newborn, makes the development of alternative reagents desirable. We compared Rh immune globulin and 6 human monoclonal anti-D antibodies (MoAnti-D) with differing isotypes and specificities for their ability to opsonize erythrocytes and inhibit platelet phagocytosis in an in vitro assay. Results demonstrated that opsonization of erythrocytes with Rh immune globulin significantly (P < .001) reduced phagocytosis of fluorescently labeled opsonized platelets in an Fc-dependent manner. Of the MoAnti-D that shared specificity but differed in isotype, only IgG3 antibodies could significantly (P < .001) inhibit platelet phagocytosis. In contrast, 2 MoAnti-D shared isotypes and differed in specificity; however, only one could significantly (P < .001) inhibit platelet phagocytosis. The results suggest that MoAnti-D epitope specificity and isotypes are critical requirements for optimal inhibition of opsonized platelet phagocytosis.</p>}}, author = {{Kjaersgaard, Mimi and Aslam, Rukhsana and Kim, Michael and Speck, Edwin R and Freedman, John and Stewart, Donald I H and Wiersma, Erik J and Semple, John W}}, issn = {{0006-4971}}, keywords = {{Antibodies, Monoclonal/immunology; Antigens, Human Platelet/immunology; Autoantibodies/immunology; Blood Platelets/immunology; Epitopes/immunology; Humans; Immunoglobulin Isotypes; Opsonin Proteins; Phagocytosis; Purpura, Thrombocytopenic, Idiopathic/immunology; Rh Isoimmunization; Rho(D) Immune Globulin/immunology}}, language = {{eng}}, month = {{08}}, number = {{4}}, pages = {{61--1359}}, publisher = {{American Society of Hematology}}, series = {{Blood}}, title = {{Epitope specificity and isotype of monoclonal anti-D antibodies dictate their ability to inhibit phagocytosis of opsonized platelets}}, url = {{http://dx.doi.org/10.1182/blood-2007-03-079848}}, doi = {{10.1182/blood-2007-03-079848}}, volume = {{110}}, year = {{2007}}, }