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The non-haemostatic role of platelets in systemic lupus erythematosus

Nature Reviews Rheumatology volume 14, pages 195–213 (2018)Cite this article

Subjects

Key Points

  • Platelets contain and can synthesize molecules capable of modulating adaptive and innate immune responses.

  • In systemic lupus erythematosus (SLE), platelets are activated, their abundance often reflects disease activity, and treatments for SLE can affect platelet functions.

  • Platelets express immune receptors, including FcγRIIA and Toll-like receptors, that could initiate platelet activation in SLE.

  • Complement activation during the course of SLE implicates platelets and supports a role for platelets in thrombosis in SLE.

  • Molecules such as CD40 ligand, IL-1, serotonin and danger-associated molecular patterns are present in platelets and can participate in the pathogenesis of SLE.

  • Platelets can shed membrane vesicles, known as microparticles or microvesicles, that convey inflammatory mediators and disseminate mitochondrial antigens for the formation of immune complexes.

Abstract

Dysregulation of lymphocyte function, accumulation of autoantibodies and defective clearance of circulating immune complexes and apoptotic cells are hallmarks of systemic lupus erythematosus (SLE). Moreover, it is now evident that an intricate interplay between the adaptive and innate immune systems contributes to the pathogenesis of SLE, ultimately resulting in chronic inflammation and organ damage. Platelets circulate in the blood and are chiefly recognized for their role in the prevention of bleeding and promotion of haemostasis; however, accumulating evidence points to a role for platelets in both adaptive and innate immunity. Through a broad repertoire of receptors, platelets respond promptly to immune complexes, complement and damage-associated molecular patterns, and represent a major reservoir of immunomodulatory molecules in the circulation. Furthermore, evidence suggests that platelets are activated in patients with SLE, and that they could contribute to the circulatory autoantigenic load through the release of microparticles and mitochondrial antigens. Herein, we highlight how platelets contribute to the immune response and review evidence implicating platelets in the pathogenesis of SLE.

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Figure 1: Megakaryocytes contribute to the immunomodulatory content of platelets.
Figure 2: Platelet activation pathways and putative effects of activated platelets in SLE pathogenesis.
Figure 3: Mechanisms potentially involved in the dysregulation of platelet serotonin levels in SLE.
Figure 4: Platelets release microparticles and mitochondrial antigens.

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Authors and Affiliations

  1. Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Lund, Sweden

    Petrus Linge & Anders A. Bengtsson

  2. Division of Rheumatology, Department of Medicine, CHU de Québec–Université Laval, Quebec City, Quebec, Canada

    Paul R. Fortin

  3. Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec–Université Laval, Quebec City, Quebec, Canada

    Paul R. Fortin & Eric Boilard

  4. Department of Medicine, Division of Rheumatology, University of Washington, Seattle, WA, USA

    Christian Lood

  5. Canadian National Transplantation Research Program, Edmonton, Alberta, Canada

    Eric Boilard

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E.B. and C.P.L. researched data for the article. E.B., C.P.L. and C.J.L. wrote the article. All authors made substantial contributions to discussions of the content and reviewed and/or edited the manuscript before submission.

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Linge, P., Fortin, P., Lood, C. et al. The non-haemostatic role of platelets in systemic lupus erythematosus. Nat Rev Rheumatol 14, 195–213 (2018). https://doi.org/10.1038/nrrheum.2018.38

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