The Experts below are selected from a list of 1002 Experts worldwide ranked by ideXlab platform
Javier Cabiedes - One of the best experts on this subject based on the ideXlab platform.
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characterization of monoclonal anti β2 glycoprotein i and anti Prothrombin Antibody fragments generated by phage display from a patient with primary antiphospholipid syndrome
Journal of Autoimmunity, 2006Co-Authors: Marisol Languren, Baltazar Becerril, Antonio R Cabral, Luisa E Fernandezaltuna, Virginia Pascual, Diego F Hernandezramirez, Javier CabiedesAbstract:Abstract The molecular structure of antibodies associated with autoimmune thrombosis is beginning to be understood. We describe the binding specificities and sequence analysis of anti-β 2 -glycoprotein-I (anti-β 2 GP-I) or anti-Prothrombin (anti-PT) Antibody fragments generated by phage display from a patient with primary antiphospholipid syndrome (APS). We obtained 39 positive clones, two that had the correct size reacted with β 2 GP-I (Beta 1 and Beta 2). Ten clones with the same restrictive pattern recognized PT (Prot 1) and cross-reacted with β 2 GP-I. All three clones recognized anionic and zwitterionic phospholipids. The V H regions of both anti-β 2 GP-I clones are members of the VH4 family. Prot 1 has a V H segment of the VH3 family. The Beta 1 J H segments are J H 5b and J H 4b for Beta 2 and Prot 1. V L genes are V λ 1, 3 and 1, respectively. No J L was identified for Beta 1, while Beta 2 and Prot 1 carry J λ 3b genes. Beta 1 and Beta 2 carry highly conserved germ-line V H and V L genes. Mutations of the Prot 1 gene appear to be antigen-dependent, most are hotspot mutations located in the CDR 1 and 2 regions. Our work suggests that some anti-β 2 GP-I from patients with primary APS are natural autoantibodies. Our work may also help to explain the frequent coexistence of anti-β 2 GP-I and anti-PT in the same patient.
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characterization of monoclonal anti β2 glycoprotein i and anti Prothrombin Antibody fragments generated by phage display from a patient with primary antiphospholipid syndrome
Journal of Autoimmunity, 2006Co-Authors: Marisol Languren, Baltazar Becerril, Antonio R Cabral, Luisa E Fernandezaltuna, Virginia Pascual, Diego F Hernandezramirez, Javier CabiedesAbstract:The molecular structure of antibodies associated with autoimmune thrombosis is beginning to be understood. We describe the binding specificities and sequence analysis of anti-beta2-glycoprotein-I (anti-beta2GP-I) or anti-Prothrombin (anti-PT) Antibody fragments generated by phage display from a patient with primary antiphospholipid syndrome (APS). We obtained 39 positive clones, two that had the correct size reacted with beta2GP-I (Beta 1 and Beta 2). Ten clones with the same restrictive pattern recognized PT (Prot 1) and cross-reacted with beta2GP-I. All three clones recognized anionic and zwitterionic phospholipids. The V(H) regions of both anti-beta2GP-I clones are members of the VH4 family. Prot 1 has a V(H) segment of the VH3 family. The Beta 1 J(H) segments are J(H)5b and J(H)4b for Beta 2 and Prot 1. V(L) genes are V(lambda)1, 3 and 1, respectively. No J(L) was identified for Beta 1, while Beta 2 and Prot 1 carry J(lambda)3b genes. Beta 1 and Beta 2 carry highly conserved germ-line V(H) and V(L) genes. Mutations of the Prot 1 gene appear to be antigen-dependent, most are hotspot mutations located in the CDR 1 and 2 regions. Our work suggests that some anti-beta2GP-I from patients with primary APS are natural autoantibodies. Our work may also help to explain the frequent coexistence of anti-beta2GP-I and anti-PT in the same patient.
Howard A. Liebman - One of the best experts on this subject based on the ideXlab platform.
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a fatal bleeding disorder due to Antibody mediated acquired factor x and Prothrombin deficiency
Blood, 2006Co-Authors: Leanne Rochanda, Gregory J Del Zoppo, Donald I. Feinstein, Howard A. LiebmanAbstract:Abnormalities in hemostasis are well described in patients with malignant disorders. While hemostatic activation resulting in thrombosis is most often described, acquired hemorrhagic disorders have also been reported. We report a case of a fatal hemorrhagic disorder in a lymphoma patient due to an acquired Factor X and Prothrombin deficiency. The patient’s plasma contained a non-inhibitory IgG Antibody that cross-reacted with and cleared from the circulation both Factor X and Prothrombin. The patient was a 72 year old male who was first noted to have persistant bleeding after angioplasty in 1991. Over the subsequent 10 years he had repeated bleeding episodes and was noted to have a prolonged PT and a PTT which corrected with a 50–50 mix of normal plasma. In 2002 he was diagnosed with a monocytooid B cell lymphoma. In April 2002 the patient had an extensive hemostatic evaluation by one of the authors (DIF) which is included in Table 1. These studies again showed a prolonged PT and aPTT which corrected with a 50–50 mix. Factor II activity and antigen were significantly reduced. While Factor X activity was low normal, Factor X antigen was decreased compared to the normal controls. Patient IgG was then isolated by Stap A chromatography and anit-Prothrombin antibodies directed were isolated by affinity chromatography on Prothrombin-sepharose. Isolated antibodies were subtyped as an IgG subclass 4. The antibodies were assayed for their interaction with Prothrombin by a direct binding ELISA and found to be calcium dependent since they did not bind in the presence of 5 mM EDTA. The interaction of the affinity isolated Antibody with Prothrombin, Factor X and Factor IX was assessed using the Western Blot method. Surprisingly, the Antibody also bound strongly to Factor X and to a lesser degree to Factor IX. Western blot analysis of the Factor X and Factor IX preparations using a monoclonal anti-Prothrombin Antibody failed to demonstrate any Prothrombin contamination of these proteins. A competition ELISA using Prothrombin, Factor X and Factor IX showed that the Antibody had a 3-fold greater affinity to Factor X then Prothrombin. A Western blot using purified Prothrombin fragment F1.2 confirmed that the Antibody bound to a metal dependent conformational determinant on the amino-terminal Gla containing region of Factor II. In April 2003 the patient developed weakness in his left leg and was found to have a right parietotemporal subdural hematoma. Factor II activity was again only 34%. Intravenous IgG 1gm/kg on two separate days did not correct his coagulation studies. In June 2003 the patient developed a new large left sudural hematoma. He rapidly deteriorated and expired. We previosuly reported a lymphoma patient who developed acquired Prothrombin deficiency associated with a non-inhibitory Antibody (Cancer2001; 91: 636), however, this is the first reported case of combined acquired Factor X and Prothrombin deficiency due to a cross-reactive non-inhibitory IgG Antibody.
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a fatal bleeding disorder due to Antibody mediated acquired factor x and Prothrombin deficiency
Blood, 2006Co-Authors: Leanne Rochanda, Gregory J Del Zoppo, Donald I. Feinstein, Howard A. LiebmanAbstract:Abnormalities in hemostasis are well described in patients with malignant disorders. While hemostatic activation resulting in thrombosis is most often described, acquired hemorrhagic disorders have also been reported. We report a case of a fatal hemorrhagic disorder in a lymphoma patient due to an acquired Factor X and Prothrombin deficiency. The patient’s plasma contained a non-inhibitory IgG Antibody that cross-reacted with and cleared from the circulation both Factor X and Prothrombin. The patient was a 72 year old male who was first noted to have persistant bleeding after angioplasty in 1991. Over the subsequent 10 years he had repeated bleeding episodes and was noted to have a prolonged PT and a PTT which corrected with a 50–50 mix of normal plasma. In 2002 he was diagnosed with a monocytooid B cell lymphoma. In April 2002 the patient had an extensive hemostatic evaluation by one of the authors (DIF) which is included in Table 1. These studies again showed a prolonged PT and aPTT which corrected with a 50–50 mix. Factor II activity and antigen were significantly reduced. While Factor X activity was low normal, Factor X antigen was decreased compared to the normal controls. Patient IgG was then isolated by Stap A chromatography and anit-Prothrombin antibodies directed were isolated by affinity chromatography on Prothrombin-sepharose. Isolated antibodies were subtyped as an IgG subclass 4. The antibodies were assayed for their interaction with Prothrombin by a direct binding ELISA and found to be calcium dependent since they did not bind in the presence of 5 mM EDTA. The interaction of the affinity isolated Antibody with Prothrombin, Factor X and Factor IX was assessed using the Western Blot method. Surprisingly, the Antibody also bound strongly to Factor X and to a lesser degree to Factor IX. Western blot analysis of the Factor X and Factor IX preparations using a monoclonal anti-Prothrombin Antibody failed to demonstrate any Prothrombin contamination of these proteins. A competition ELISA using Prothrombin, Factor X and Factor IX showed that the Antibody had a 3-fold greater affinity to Factor X then Prothrombin. A Western blot using purified Prothrombin fragment F1.2 confirmed that the Antibody bound to a metal dependent conformational determinant on the amino-terminal Gla containing region of Factor II. In April 2003 the patient developed weakness in his left leg and was found to have a right parietotemporal subdural hematoma. Factor II activity was again only 34%. Intravenous IgG 1gm/kg on two separate days did not correct his coagulation studies. In June 2003 the patient developed a new large left sudural hematoma. He rapidly deteriorated and expired. We previosuly reported a lymphoma patient who developed acquired Prothrombin deficiency associated with a non-inhibitory Antibody (Cancer2001; 91: 636), however, this is the first reported case of combined acquired Factor X and Prothrombin deficiency due to a cross-reactive non-inhibitory IgG Antibody.
Marisol Languren - One of the best experts on this subject based on the ideXlab platform.
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characterization of monoclonal anti β2 glycoprotein i and anti Prothrombin Antibody fragments generated by phage display from a patient with primary antiphospholipid syndrome
Journal of Autoimmunity, 2006Co-Authors: Marisol Languren, Baltazar Becerril, Antonio R Cabral, Luisa E Fernandezaltuna, Virginia Pascual, Diego F Hernandezramirez, Javier CabiedesAbstract:Abstract The molecular structure of antibodies associated with autoimmune thrombosis is beginning to be understood. We describe the binding specificities and sequence analysis of anti-β 2 -glycoprotein-I (anti-β 2 GP-I) or anti-Prothrombin (anti-PT) Antibody fragments generated by phage display from a patient with primary antiphospholipid syndrome (APS). We obtained 39 positive clones, two that had the correct size reacted with β 2 GP-I (Beta 1 and Beta 2). Ten clones with the same restrictive pattern recognized PT (Prot 1) and cross-reacted with β 2 GP-I. All three clones recognized anionic and zwitterionic phospholipids. The V H regions of both anti-β 2 GP-I clones are members of the VH4 family. Prot 1 has a V H segment of the VH3 family. The Beta 1 J H segments are J H 5b and J H 4b for Beta 2 and Prot 1. V L genes are V λ 1, 3 and 1, respectively. No J L was identified for Beta 1, while Beta 2 and Prot 1 carry J λ 3b genes. Beta 1 and Beta 2 carry highly conserved germ-line V H and V L genes. Mutations of the Prot 1 gene appear to be antigen-dependent, most are hotspot mutations located in the CDR 1 and 2 regions. Our work suggests that some anti-β 2 GP-I from patients with primary APS are natural autoantibodies. Our work may also help to explain the frequent coexistence of anti-β 2 GP-I and anti-PT in the same patient.
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characterization of monoclonal anti β2 glycoprotein i and anti Prothrombin Antibody fragments generated by phage display from a patient with primary antiphospholipid syndrome
Journal of Autoimmunity, 2006Co-Authors: Marisol Languren, Baltazar Becerril, Antonio R Cabral, Luisa E Fernandezaltuna, Virginia Pascual, Diego F Hernandezramirez, Javier CabiedesAbstract:The molecular structure of antibodies associated with autoimmune thrombosis is beginning to be understood. We describe the binding specificities and sequence analysis of anti-beta2-glycoprotein-I (anti-beta2GP-I) or anti-Prothrombin (anti-PT) Antibody fragments generated by phage display from a patient with primary antiphospholipid syndrome (APS). We obtained 39 positive clones, two that had the correct size reacted with beta2GP-I (Beta 1 and Beta 2). Ten clones with the same restrictive pattern recognized PT (Prot 1) and cross-reacted with beta2GP-I. All three clones recognized anionic and zwitterionic phospholipids. The V(H) regions of both anti-beta2GP-I clones are members of the VH4 family. Prot 1 has a V(H) segment of the VH3 family. The Beta 1 J(H) segments are J(H)5b and J(H)4b for Beta 2 and Prot 1. V(L) genes are V(lambda)1, 3 and 1, respectively. No J(L) was identified for Beta 1, while Beta 2 and Prot 1 carry J(lambda)3b genes. Beta 1 and Beta 2 carry highly conserved germ-line V(H) and V(L) genes. Mutations of the Prot 1 gene appear to be antigen-dependent, most are hotspot mutations located in the CDR 1 and 2 regions. Our work suggests that some anti-beta2GP-I from patients with primary APS are natural autoantibodies. Our work may also help to explain the frequent coexistence of anti-beta2GP-I and anti-PT in the same patient.
Leanne Rochanda - One of the best experts on this subject based on the ideXlab platform.
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a fatal bleeding disorder due to Antibody mediated acquired factor x and Prothrombin deficiency
Blood, 2006Co-Authors: Leanne Rochanda, Gregory J Del Zoppo, Donald I. Feinstein, Howard A. LiebmanAbstract:Abnormalities in hemostasis are well described in patients with malignant disorders. While hemostatic activation resulting in thrombosis is most often described, acquired hemorrhagic disorders have also been reported. We report a case of a fatal hemorrhagic disorder in a lymphoma patient due to an acquired Factor X and Prothrombin deficiency. The patient’s plasma contained a non-inhibitory IgG Antibody that cross-reacted with and cleared from the circulation both Factor X and Prothrombin. The patient was a 72 year old male who was first noted to have persistant bleeding after angioplasty in 1991. Over the subsequent 10 years he had repeated bleeding episodes and was noted to have a prolonged PT and a PTT which corrected with a 50–50 mix of normal plasma. In 2002 he was diagnosed with a monocytooid B cell lymphoma. In April 2002 the patient had an extensive hemostatic evaluation by one of the authors (DIF) which is included in Table 1. These studies again showed a prolonged PT and aPTT which corrected with a 50–50 mix. Factor II activity and antigen were significantly reduced. While Factor X activity was low normal, Factor X antigen was decreased compared to the normal controls. Patient IgG was then isolated by Stap A chromatography and anit-Prothrombin antibodies directed were isolated by affinity chromatography on Prothrombin-sepharose. Isolated antibodies were subtyped as an IgG subclass 4. The antibodies were assayed for their interaction with Prothrombin by a direct binding ELISA and found to be calcium dependent since they did not bind in the presence of 5 mM EDTA. The interaction of the affinity isolated Antibody with Prothrombin, Factor X and Factor IX was assessed using the Western Blot method. Surprisingly, the Antibody also bound strongly to Factor X and to a lesser degree to Factor IX. Western blot analysis of the Factor X and Factor IX preparations using a monoclonal anti-Prothrombin Antibody failed to demonstrate any Prothrombin contamination of these proteins. A competition ELISA using Prothrombin, Factor X and Factor IX showed that the Antibody had a 3-fold greater affinity to Factor X then Prothrombin. A Western blot using purified Prothrombin fragment F1.2 confirmed that the Antibody bound to a metal dependent conformational determinant on the amino-terminal Gla containing region of Factor II. In April 2003 the patient developed weakness in his left leg and was found to have a right parietotemporal subdural hematoma. Factor II activity was again only 34%. Intravenous IgG 1gm/kg on two separate days did not correct his coagulation studies. In June 2003 the patient developed a new large left sudural hematoma. He rapidly deteriorated and expired. We previosuly reported a lymphoma patient who developed acquired Prothrombin deficiency associated with a non-inhibitory Antibody (Cancer2001; 91: 636), however, this is the first reported case of combined acquired Factor X and Prothrombin deficiency due to a cross-reactive non-inhibitory IgG Antibody.
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a fatal bleeding disorder due to Antibody mediated acquired factor x and Prothrombin deficiency
Blood, 2006Co-Authors: Leanne Rochanda, Gregory J Del Zoppo, Donald I. Feinstein, Howard A. LiebmanAbstract:Abnormalities in hemostasis are well described in patients with malignant disorders. While hemostatic activation resulting in thrombosis is most often described, acquired hemorrhagic disorders have also been reported. We report a case of a fatal hemorrhagic disorder in a lymphoma patient due to an acquired Factor X and Prothrombin deficiency. The patient’s plasma contained a non-inhibitory IgG Antibody that cross-reacted with and cleared from the circulation both Factor X and Prothrombin. The patient was a 72 year old male who was first noted to have persistant bleeding after angioplasty in 1991. Over the subsequent 10 years he had repeated bleeding episodes and was noted to have a prolonged PT and a PTT which corrected with a 50–50 mix of normal plasma. In 2002 he was diagnosed with a monocytooid B cell lymphoma. In April 2002 the patient had an extensive hemostatic evaluation by one of the authors (DIF) which is included in Table 1. These studies again showed a prolonged PT and aPTT which corrected with a 50–50 mix. Factor II activity and antigen were significantly reduced. While Factor X activity was low normal, Factor X antigen was decreased compared to the normal controls. Patient IgG was then isolated by Stap A chromatography and anit-Prothrombin antibodies directed were isolated by affinity chromatography on Prothrombin-sepharose. Isolated antibodies were subtyped as an IgG subclass 4. The antibodies were assayed for their interaction with Prothrombin by a direct binding ELISA and found to be calcium dependent since they did not bind in the presence of 5 mM EDTA. The interaction of the affinity isolated Antibody with Prothrombin, Factor X and Factor IX was assessed using the Western Blot method. Surprisingly, the Antibody also bound strongly to Factor X and to a lesser degree to Factor IX. Western blot analysis of the Factor X and Factor IX preparations using a monoclonal anti-Prothrombin Antibody failed to demonstrate any Prothrombin contamination of these proteins. A competition ELISA using Prothrombin, Factor X and Factor IX showed that the Antibody had a 3-fold greater affinity to Factor X then Prothrombin. A Western blot using purified Prothrombin fragment F1.2 confirmed that the Antibody bound to a metal dependent conformational determinant on the amino-terminal Gla containing region of Factor II. In April 2003 the patient developed weakness in his left leg and was found to have a right parietotemporal subdural hematoma. Factor II activity was again only 34%. Intravenous IgG 1gm/kg on two separate days did not correct his coagulation studies. In June 2003 the patient developed a new large left sudural hematoma. He rapidly deteriorated and expired. We previosuly reported a lymphoma patient who developed acquired Prothrombin deficiency associated with a non-inhibitory Antibody (Cancer2001; 91: 636), however, this is the first reported case of combined acquired Factor X and Prothrombin deficiency due to a cross-reactive non-inhibitory IgG Antibody.
Diego F Hernandezramirez - One of the best experts on this subject based on the ideXlab platform.
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characterization of monoclonal anti β2 glycoprotein i and anti Prothrombin Antibody fragments generated by phage display from a patient with primary antiphospholipid syndrome
Journal of Autoimmunity, 2006Co-Authors: Marisol Languren, Baltazar Becerril, Antonio R Cabral, Luisa E Fernandezaltuna, Virginia Pascual, Diego F Hernandezramirez, Javier CabiedesAbstract:Abstract The molecular structure of antibodies associated with autoimmune thrombosis is beginning to be understood. We describe the binding specificities and sequence analysis of anti-β 2 -glycoprotein-I (anti-β 2 GP-I) or anti-Prothrombin (anti-PT) Antibody fragments generated by phage display from a patient with primary antiphospholipid syndrome (APS). We obtained 39 positive clones, two that had the correct size reacted with β 2 GP-I (Beta 1 and Beta 2). Ten clones with the same restrictive pattern recognized PT (Prot 1) and cross-reacted with β 2 GP-I. All three clones recognized anionic and zwitterionic phospholipids. The V H regions of both anti-β 2 GP-I clones are members of the VH4 family. Prot 1 has a V H segment of the VH3 family. The Beta 1 J H segments are J H 5b and J H 4b for Beta 2 and Prot 1. V L genes are V λ 1, 3 and 1, respectively. No J L was identified for Beta 1, while Beta 2 and Prot 1 carry J λ 3b genes. Beta 1 and Beta 2 carry highly conserved germ-line V H and V L genes. Mutations of the Prot 1 gene appear to be antigen-dependent, most are hotspot mutations located in the CDR 1 and 2 regions. Our work suggests that some anti-β 2 GP-I from patients with primary APS are natural autoantibodies. Our work may also help to explain the frequent coexistence of anti-β 2 GP-I and anti-PT in the same patient.
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characterization of monoclonal anti β2 glycoprotein i and anti Prothrombin Antibody fragments generated by phage display from a patient with primary antiphospholipid syndrome
Journal of Autoimmunity, 2006Co-Authors: Marisol Languren, Baltazar Becerril, Antonio R Cabral, Luisa E Fernandezaltuna, Virginia Pascual, Diego F Hernandezramirez, Javier CabiedesAbstract:The molecular structure of antibodies associated with autoimmune thrombosis is beginning to be understood. We describe the binding specificities and sequence analysis of anti-beta2-glycoprotein-I (anti-beta2GP-I) or anti-Prothrombin (anti-PT) Antibody fragments generated by phage display from a patient with primary antiphospholipid syndrome (APS). We obtained 39 positive clones, two that had the correct size reacted with beta2GP-I (Beta 1 and Beta 2). Ten clones with the same restrictive pattern recognized PT (Prot 1) and cross-reacted with beta2GP-I. All three clones recognized anionic and zwitterionic phospholipids. The V(H) regions of both anti-beta2GP-I clones are members of the VH4 family. Prot 1 has a V(H) segment of the VH3 family. The Beta 1 J(H) segments are J(H)5b and J(H)4b for Beta 2 and Prot 1. V(L) genes are V(lambda)1, 3 and 1, respectively. No J(L) was identified for Beta 1, while Beta 2 and Prot 1 carry J(lambda)3b genes. Beta 1 and Beta 2 carry highly conserved germ-line V(H) and V(L) genes. Mutations of the Prot 1 gene appear to be antigen-dependent, most are hotspot mutations located in the CDR 1 and 2 regions. Our work suggests that some anti-beta2GP-I from patients with primary APS are natural autoantibodies. Our work may also help to explain the frequent coexistence of anti-beta2GP-I and anti-PT in the same patient.
