John Semple

My research is aimed at understanding the cellular immune mechanisms responsible for the generation of IgG antibodies that recognize platelet antigens. These antibodies can lead to clinically significant adverse effects such as autoimmunity causing immune thrombocytopenia (ITP) and alloimmunity causing platelet transfusion refractoriness. In ITP, we are interested in how platelet antigens are processed and presented by antigen-presenting cells to activate T lymphocytes. In platelet refractoriness, we study the pro-inflammatory nature of platelets responsible for adverse reactions during platelet transfusions, particularly how platelet Toll-like receptor expression modulates innate immune mechanisms. We also study the recipient immune mechanisms that cause Transfusion Related Acute Lung Injury (TRALI), a serious complication of transfusion. We are also interested in understanding how therapies such as intravenous gammaglobulin (IVIg) and anti-D increase platelet counts in immune thrombocytopenic disorders.

Select Publications:

Palm F et al. Phenotypic characterization of acoustically enriched extracellular vesicles from pathogen-activated platelets. J Innate Immun. 2023 May 27, doi: 10.1159/000531266.

Provan AB et al. Recent advances in the mechanisms and treatment of immune thrombocytopenia. Lancet, EBioMedicine. 76: 103820, 2022. https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00009-3/fulltext.

Linge P et al. Enrichment of complement, immunoglobulins and autoantibody targets in the proteome of platelets from patients with Systemic Lupus Erythematosus (SLE). Thromb Haemost. 122(9):1486-1501, 2022.

Martínez-Botía P et al. Platelet Proteomics to Understand the Pathophysiology of Immune Thrombocytopenia: Studies in Mouse Models. Blood Adv. 14;6(11):3529-3534, 2022.

Marcoux G et al. Platelet-derived extracellular vesicles contain an active proteasome involved in protein processing for antigen presentation via MHC class I. Blood. 138(25):2607-2620, 2021.

Lee, E-J et al. Thrombocytopenia following Pfizer and Moderna SARS/CoV-2 vaccination. Amer J Hematol. 96(5):534-537, 2021. 

McVey MJ et al. Platelet extracellular vesicles mediate Transfusion-Related Acute Lung Injury by imbalancing the sphingolipid rheostat. Blood. 137(5):690-701, 2021.

Kapur R et al. Thrombopoietin receptor agonist (TPO-RA) treatment raises platelet counts and reduces anti-platelet antibody levels in mice with immune thrombocytopenia (ITP). Platelets. 31(3):399-402, 2020.

Semple JW et al. An update on the pathophysiology of immune thrombocytopenia (ITP). Curr Opin Hematol. 27(6):423-429, 2020.

Maouia A et al. The immune nature of platelets revisited. Transfusion Med. Rev. 34(4):209-220, 2020.

Kapur R et al. Osteopontin mediates murine transfusion-related acute lung injury through stimulation of pulmonary neutrophil accumulation. Blood 134(1):74-84, 2019.

Semple JW et al. Transfusion-associated circulatory overload and transfusion-related acute lung injury. Blood. 133(17):1840-1853, 2019.

Kapur R et al. Gastrointestinal microbiota contributes to the development of murine transfusion-related acute lung injury. Blood Adv. 2(13):1651-1663, 2018.

Aslam R et al. Intravenous immunoglobulin (IVIg) treatment increases the expression of Myeloid-Derived Suppressor Cells (MDSC) in the spleens of patients with immune thrombocytopenia (ITP). Br J Haematol. 181(2):262-264, 2018.

Kapur R et al. A highly purified form of staphylococcal protein A alleviates murine immune thrombocytopenia (ITP). Brit J Haematol. 183(3):501-503, 2018. (Senior Responsible Author).
 

Guo L et al. Anti-platelet antibody-induced thrombocytopenia does not correlate with megakaryocyte abnormalities in murine immune thrombocytopenia (ITP). Scand J Immunol. 88(1):e12678, 2018. (PhD Supervisor, Senior Author).

Kapur R, Kim M, Shanmugabhavananthan S, Liu J, Li Y, Aslam R, Tabuchi A, Speck ER, Zufferey A, Kuebler WM, Semple JW. T-Regulatory Cells and Dendritic Cells Protect Against Transfusion-Related Acute Lung Injury via IL-10. Blood 2017 Feb 15. pii: blood-2016-12-758185. doi: 10.1182/blood-2016-12-758185.

Aslam R, Burak WR, Segel GB, McVey M, Spence SA, Semple JW. Intravenous immunoglobulin (IVIg) treatment increases the expression of Myeloid-Derived Suppressor Cells (MDSC) in the spleens of patients with immune thrombocytopenia (ITP). Br J Haematol. 2017 Feb 6. doi: 10.1111/bjh.14542.

Kapur R, Aslam R, Guo L, Kim M, Segel GB, Ni H, Semple JW. Thymic-Derived Tolerizing Dendritic Cells Are Up-Regulated in the Spleen upon Treatment with Intravenous Immunoglobulin in a Murine Model of Immune Thrombocytopenia. Platelets. 25:1-4, 2016.

Aslam R,  Kapur R, Segel GB, Guo L, Zufferey A, Ni H, Semple JW. The spleen dictates platelet destruction, anti-platelet antibody production and lymphocyte distribution patterns in a murine model of immune thrombocytopenia (ITP). Exp Hematol 44(10):924-930, 2016.

Kapur R, Kim M, Rondina MT, Porcelijn L, Semple JW. Elevation of C-Reactive Protein Levels in Patients with Transfusion-Related Acute Lung Injury. Oncotarget. 22;7(47):78048-78054, 2016.

Aslam R, Segel GB, Burack R, Spence SA, Speck ER, Guo L, Semple JW. Splenic lymphocyte subtypes in immune thrombocytopenia (ITP: Heightened presence of a subtype of B regulatory cells. Brit J Haematol. 173(1):159-60, 2016.

Guo L, Kapur R, Aslam R, Speck ER, Zufferey A, Zhao Y, Kim M, Lazarus AH, Ni H, Semple JW. CD20+ B cell depletion therapy suppresses murine CD8+ T cell-mediated immune thrombocytopenia (ITP). Blood 127(6):735-8, 2016.

Kapur R, Kim M, Shanmugabhavananthan S, Liu J, Li Y, Semple JW. C-reactive Protein (CRP) Enhances Murine Antibody-Mediated Transfusion-Related Acute Lung Injury (TRALI). Blood 126(25):2747-2751, 2015.

McKenzie CGJ, Kim M, Singh TK, Milev Y, Freedman J, Semple JW. Peripheral blood monocyte-derived chemokine blockade prevents murine antibody-mediated transfusion related acute lung injury (TRALI). Blood. 123(22):3496-3503, 2014. 

Guo L, Yang L, Speck ER, Aslam R, Kim M, Mckenzie CGJ, Lazarus AH, Ni H, Hou M, Freedman J, Semple JW. Allogeneic platelet transfusions prevent murine T cell-mediated immune thrombocytopenia (ITP). Blood. 123(3):422-427, 2014.

Aslam R, Hu Y, Gebremeskel S, Segel GB, Speck ER, Guo L, Kim M, Ni H, Freedman J, Semple JW. Thymic Retention of CD4+CD25+FoxP3+ T regulatory cells is associated with their peripheral deficiency and thrombocytopenia in a murine model of immune thrombocytopenia (ITP). Blood. 120(10):2127-2132, 2012.

Semple JW, Kim M, Hou J, Lee YJ, Tabuchi A, Kuebler WM, Chai Z-W, Lazarus AH. Intravenous immunoglobulin (IVIg) therapy prevents murine antibody-mediated Transfusion Related Acute Lung Injury (TRALI) at the level of neutrophil activation.   PLoS One 7(2):e31357, 2012.

Semple JW, Italiano Jr JE, Freedman J.  Platelets and the immune continuum.  Nature Rev Immunol. 11(4):264-274, 2011.  (Senior Responsible Author).