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Pathophysiology of immune-mediated disorders of platelets and endothelium

Introduction

The research line is focused on unraveling the pathophysiology and improving the diagnostics of benign immune-hematological disorders. This includes immune-responses towards 1) Platelets: the autoimmune bleeding disorder Immune Thrombocytopenia (ITP), vaccine-induced thrombotic thrombocytopenia (VITT), heparin-induced thrombocytopenia (HIT), platelet transfusion refractoriness and towards 2) Endothelium: particularly Transfusion-related acute lung injury (TRALI), and also Transfusion-associated circulatory overload (TACO); both in which the pulmonary endothelium is targeted resulting in acute respiratory distress and pulmonary edema, and together they are the leading causes of Transfusion-related mortality. We work in close collaboration with Sanquin Diagnostics, which functions as the national reference center for antibody-testing in ITP patients, and for diagnostics for suspected VITT, HIT and TRALI patients. In addition, we collaborate with clinicians who treat patients with the aforementioned immune-hematological disorders. Furthermore, we utilize and develop clinically-relevant animal models of these immune-hematological disorders to obtain insights into the pathophysiology, which is overall incompletely understood. Collectively, we aim to identify much needed novel and specific biomarkers and pre-clinical therapeutic targets, and use the obtained pathophysiological insights to innovate diagnostic approaches.

Infographic research lines

 

Key publications since 2019 (selection)

OrcidID Dr. Rick Kapur

1) Amini SN, Nelson V, Porcelijn L, Netelenbos T, Zwaginga JJ, de Haas M, Schipperus M, and Kapur R. The interplay between GPIb/IX-antibodies, platelet hepatic sequestration, and TPO levels in patients with chronic ITP. Blood Advances 2022; doi: 10.1182/bloodadvances.2022007751. Online ahead of print.

2) Morsing SKH, Zeeuw van der Laan EAN, van Stalborch AD, van Buul JD, Vlaar APJ, and Kapur R. Endothelial cells of pulmonary origin display unique sensitivity to the bacterial endotoxin lipopolysaccharide. Physiological Reports 2022;10(8):e15271.

3) Nelson VS, Jolink AC, Amini SN, Zwaginga JJ, Netelenbos T, Semple JW, Porcelijn L, de Haas M, Schipperus MR, and Kapur R. Platelets in ITP: Victims in Charge of Their Own Fate? Cells 2021;10(11):3235.

4) Jolink AC, Nelson VS, Schipperus MR, Amini SN, Vidarsson G, van der Schoot CE, Porcelijn L, de Haas M, and Kapur R. Potential Diagnostic Approaches for Prediction of Therapeutic Responses in Immune Thrombocytopenia. Journal of Clinical Medicine 2021;10(15):3403.

5) Semple JW, Rebetz J, Maouia A, and Kapur R. An Update on the Pathophysiology of Immune Thrombocytopenia (ITP). Current Opinion in Hematology 2020; 27(6):423-429.

6) Zeeuw van der Laan EAN, van der Velden S, Porcelijn L, Semple JW, van der Schoot CE, and Kapur R. Update on the pathophysiology of transfusion-related acute lung injury (TRALI). Current Opinion in Hematology 2020; 27(6):386-391.

7) Zeeuw van der Laan EAN, van der Velden S, Bentlage AEH, Larsen MD, van Osch TLJ, Mok JY, Brasser G, Geerdes DM, Koeleman CAM, Nouta J, Semple JW, Porcelijn L, van Esch WJE, Wuhrer M, van der Schoot CE, Vidarsson G, and Kapur R. Biological and structural characterization of murine TRALI antibody reveals increased Fc-mediated complement activation. Blood Advances 2020; 4(16):3875-3885.

8) Porcelijn L, Schmidt DE, van der Schoot CE, Vidarsson G, de Haas M, and Kapur R. Anti-glycoprotein IbĪ± autoantibodies do not impair circulating thrombopoietin levels in immune thrombocytopenia patients. Haematologica 2020; 105(4):e172-e174.

9) Jongerius I, Porcelijn L, van Beek AE, Semple JW, van der Schoot CE, Vlaar AJP and Kapur R. The Role of Complement in Transfusion-Related Acute Lung Injury (TRALI). Transfusion Medicine Reviews 2019; 33(4):236-242.

10) Semple JW, Rebetz J, and Kapur R. Transfusion-associated circulatory overload and transfusion-related acute lung injury. Blood 2019; 133(17):1840-1853.

Online resource: Kapur R. Chapter on Immune Thrombocytopenia (ITP), 2021: 
https://www.pathologyoutlines.com/topic/spleenITP.html

 

Rick (K) Kapur, MD PhD Pathophysiology of immune mediated disorders
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