Co-administration of FVIII with IVIG reduces immune response to FVIII in hemophilia A mice
Afraz S. Stevic I. Matino D. Wen J. Atkinson H. Chan A.K.C. Hortelano G.
December 2022Nature Research
Scientific Reports
2022#12Issue 1
Hemophilia A is an X-linked recessive congenital bleeding disorder. Exogenous infusion of FVIII is the treatment of choice, and the development of immunoglobulins against FVIII (inhibitors) remains the major challenge in clinical management of the disease. Here, we investigated the effect of co-administration of FVIII with intravenous immunoglobulin (IVIG) on the development of inhibitors in previously untreated hemophilia A mice. A group of hemophilia A mice (C57BL/6FVIII−/−) received weekly injections of recombinant human FVIII (rFVIII) for twelve consecutive weeks while a second group received co-injections of rFVIII + IVIG. An in-house enzyme-linked immunosorbent assay (ELISA) was designed to detect antibodies to rFVIII. Every mouse in the first group developed antibodies to rFVIII. In contrast, mice treated with rFVIII + IVIG showed significantly lower antibody titers. Interestingly, when co-administration of IVIG was discontinued after 12 weeks in some mice (rFVIII continued), these mice experienced an increase in antibody titer. In contrast, mice that continued to receive rFVIII + IVIG retained significantly lower titers. In conclusion, prophylactic rFVIII co-administration with IVIG modulated the immune response to FVIII and resulted in decreased anti-FVIII antibody titer. These findings suggest that co-injection therapy with IVIG could potentially be effective in the management of hemophilia A patients at risk of inhibitor development.
Text of the article Перейти на текст статьи
Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada
School of Biomedical Engineering, McMaster University, Hamilton, ON, Canada
Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
Department of Medicine, McMaster University, Hamilton, ON, Canada
McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada
Department of Pediatrics, McMaster University, Hamilton, ON, Canada
Department of Biology, School of Science and Humanities, Nazarbayev University, Qabanbay Batyr Ave 53, Nur-Sultan, 010000, Kazakhstan
Thrombosis and Atherosclerosis Research Institute
School of Biomedical Engineering
Department of Pathology and Laboratory Medicine
Department of Medicine
McMaster Immunology Research Centre
Department of Pediatrics
Department of Biology
10 лет помогаем публиковать статьи Международный издатель
Книга Публикация научной статьи Волощук 2026 Book Publication of a scientific article 2026