V Pengo1, T Del Ross2, A Ruffatti2, E Bison3, M G Cattini3, E Pontara3, S Testa4, C Legnani5, N Pozzi6, D Peterle7, L Acquasaliente8, V De Filippis7, G Denas3. 1. Cardiology Clinic, Thrombosis Centre, Department of Cardiac Thoracic and Vascular Sciences, Italy. Electronic address: vittorio.pengo@unipd.it. 2. Rheumatology Unit, Department of Medicine, University of Padua, Italy. 3. Cardiology Clinic, Thrombosis Centre, Department of Cardiac Thoracic and Vascular Sciences, Italy. 4. Hemostasis and Thrombosis Center, District Hospital, Cremona, Italy. 5. Angiology and Blood Coagulation, University Hospital of Bologna, Italy. 6. Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, USA. 7. Laboratory of Protein Chemistry, Department of Pharmaceutical & Pharmacological Sciences, University of Padua, Italy. 8. Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, USA; Laboratory of Protein Chemistry, Department of Pharmaceutical & Pharmacological Sciences, University of Padua, Italy.
Abstract
BACKGROUND: Whether antibodies directed to β2-Glycoprotein I (aβ2GPI) are responsible for LA activity is not well defined. However, in the absence of such antibodies the molecule responsible for LA phenomenon is unknown. OBJECTIVE: The aim of this study was the biochemical identification of the target antigen epitope of aPL responsible of LA activity in the absence of aβ2GPI antibodies together with the biological and clinical characteristics of these patients in comparison with classical triple positive patients. PATIENTS/ METHODS: A comparison of patients with LA without (LA+/aβ2GPI-) and those with (LA+/aβ2GPI+) associated aβ2GPI antibodies was performed. Size exclusion chromatography and analytical chromatography were used to identify the molecule with LA activity in patients LA+/aβ2GPI-. RESULTS AND CONCLUSIONS: Analytical size-exclusion chromatography revealed a peak of 996Kd with LA activity perfectly overlapping that of IgM anti phosphatidylserine/prothrombin (aPS/PT) antibodies. Similarly, all the 25 LA+/aβ2GPI- patients were positive for aPS/PT antibodies. LA+/aβ2GPI- compared to 33 LA+/aβ2GPI+ patients turned out to be significantly older, with a lower rate of previous thromboembolic events and a weaker LA activity. Search for aPS/PT and aβ2GPI antibodies in patients with LA is useful to identify two subgroups of LA at different risk of thromboembolic events.
BACKGROUND: Whether antibodies directed to β2-Glycoprotein I (aβ2GPI) are responsible for LA activity is not well defined. However, in the absence of such antibodies the molecule responsible for LA phenomenon is unknown. OBJECTIVE: The aim of this study was the biochemical identification of the target antigen epitope of aPL responsible of LA activity in the absence of aβ2GPI antibodies together with the biological and clinical characteristics of these patients in comparison with classical triple positive patients. PATIENTS/ METHODS: A comparison of patients with LA without (LA+/aβ2GPI-) and those with (LA+/aβ2GPI+) associated aβ2GPI antibodies was performed. Size exclusion chromatography and analytical chromatography were used to identify the molecule with LA activity in patients LA+/aβ2GPI-. RESULTS AND CONCLUSIONS: Analytical size-exclusion chromatography revealed a peak of 996Kd with LA activity perfectly overlapping that of IgM anti phosphatidylserine/prothrombin (aPS/PT) antibodies. Similarly, all the 25 LA+/aβ2GPI- patients were positive for aPS/PT antibodies. LA+/aβ2GPI- compared to 33 LA+/aβ2GPI+ patients turned out to be significantly older, with a lower rate of previous thromboembolic events and a weaker LA activity. Search for aPS/PT and aβ2GPI antibodies in patients with LA is useful to identify two subgroups of LA at different risk of thromboembolic events.
Authors: Eliza Ruben; William Planer; Mathivanan Chinnaraj; Zhiwei Chen; Xiaobing Zuo; Vittorio Pengo; Vincenzo De Filippis; Ravi K Alluri; Keith R McCrae; Paolo Macor; Francesco Tedesco; Nicola Pozzi Journal: J Biol Chem Date: 2020-06-09 Impact factor: 5.157
Authors: Sahwa Elbagir; Giorgia Grosso; NasrEldeen A Mohammed; Amir I Elshafie; Elnour M Elagib; Agneta Zickert; Vivek Anand Manivel; Eleftheria Pertsinidou; Musa A M Nur; Iva Gunnarsson; Johan Rönnelid; Elisabet Svenungsson Journal: Lupus Date: 2021-05-06 Impact factor: 2.911
Authors: Charis Pericleous; Amrita D'Souza; Thomas McDonnell; Vera M Ripoll; Oliver Leach; David Isenberg; Ian Giles; Anisur Rahman Journal: Rheumatology (Oxford) Date: 2020-01-01 Impact factor: 7.580