Soluble glycoprotein VI, a specific marker of platelet activation is increased in the plasma of subjects with seropositive rheumatoid arthritis

Stack, John; Madigan, Anne; Helbert, Laura; Dunne, Eimear; Gardiner, Elizabeth E.; Andrews, Robert K.; Finan, Roisin; Smyth, Elizabeth; Kenny, Dermot; McCarthy, Géraldine

doi:10.1371/journal.pone.0188027

Cited by 15 publications

(14 citation statements)

References 22 publications

(29 reference statements)

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“…30,31 Plasma sGPVI reflects platelet activation in thrombotic conditions including microangiopathy, 32 stroke, 33 DIC, 33 and Alzheimer's disease 34 and rheumatoid arthritis. 28,35 However, elevated plasma sGPVI levels in these patient groups is surprising, as only a fraction of platelets would be exposed to collagen, FXa, or elevated shear, and neither FcgRIIA or CLEC-2 plays major roles in hemostasis/thrombosis. The recent finding that fibrin activates GPVI provides a plausible explanation for this increase.…”

Section: Introductionmentioning

confidence: 96%

Soluble GPVI is elevated in injured patients: shedding is mediated by fibrin activation of GPVI

Montague

Delierneux

Lecut³

et al. 2018

Blood Advances

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• Soluble GPVI is elevated in patients with thermal injury with sepsis, and sGPVI levels augment severity score prediction of mortality.• The GPVI ligand, fibrin, induces GPVI shedding without requirement for platelet activation or signaling Soluble glycoprotein VI (sGPVI) is shed from the platelet surface and is a marker of platelet activation in thrombotic conditions. We assessed sGPVI levels together with patient and clinical parameters in acute and chronic inflammatory conditions, including patients with thermal injury and inflammatory bowel disease and patients admitted to the intensive care unit (ICU)for elective cardiac surgery, trauma, acute brain injury, or prolonged ventilation. Plasma sGPVI was measured by enzyme-linked immunosorbent assay and was elevated on day 14 after thermal injury, and was higher in patients who developed sepsis. sGPVI levels were associated with sepsis, and the value for predicting sepsis was increased in combination with platelet count and Abbreviated Burn Severity Index. sGPVI levels positively correlated with levels of D-dimer (a fibrin degradation product) in ICU patients and patients with thermal injury. sGPVI levels in ICU patients at admission were significantly associated with 28-and 90-day mortality independent of platelet count. sGPVI levels in patients with thermal injury were associated with 28-day mortality at days 1, 14, and 21 when adjusting for platelet count. In both cohorts, sGPVI associations with mortality were stronger than D-dimer levels. Mechanistically, release of GPVI was triggered by exposure of platelets to polymerized fibrin, but not by engagement of G protein-coupled receptors by thrombin, adenosine 59-diphosphate, or thromboxane mimetics. Enhanced fibrin production in these patients may therefore contribute to the observed elevated sGPVI levels. sGPVI is an important platelet-specific marker for platelet activation that predicts sepsis progression and mortality in injured patients.

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Section: Introductionmentioning

confidence: 96%

Soluble GPVI is elevated in injured patients: shedding is mediated by fibrin activation of GPVI

Montague

Delierneux

Lecut³

et al. 2018

Blood Advances

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“…Многочисленные исследования показали, что частота артериальных и венозных тромбозов и тромбоэмболии возрастает на фоне РА, хотя причины и механизмы этих О р и г и н а л ь н ы е и с с л е д о в а н и я Параметры КСК и тромбодинамики в зависимости от СОЭ, M±σ в том числе образованные АЦЦП [4,35]. Однако, несмотря на относительный тромбоцитоз и системную активацию тромбоцитов, по мере развития патологического процесса их функциональное состояние нарушается вследствие энергетического истощения и вторичной рефрактерности [36,37], что объясняет обнаруженное нами угнетение КСК при РА.…”

Section: Discussionunclassified

“…Об этом же говорит тот факт, что при серопозитивном РА степень и скорость контракции выше, чем при серонегативном. Наиболее вероятным прямым активатором тромбоцитов при РА являются циркулирующие иммунные комплексы, действующие на тромбоциты через рецепторы FcγRIIA [4], О р и г и н а л ь н ы е и с с л е д о в а н и я…”

Section: заключениеunclassified

“…Распространенность РА в общей популяции составляет в России 0,61% [2], тогда как в других странах значение этого показателя варьирует от 0,25 до 2,5% [3]. Помимо поражения суста-вов, РА является фактором риска тяжелых внесуставных заболеваний, в том числе сопровождающихся тромботическими осложнениями, такими как инфаркт миокарда, ишемические инсульты, венозные тромбозы и тромбоэмболии [4][5][6][7][8][9].…”

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Changes in the Parameters of Thrombodynamics and Blood Clot Contraction in Patients With Rheumatoid Arthritis

Peshkova¹,

Evdokimova²,

Sibgatullin³

et al. 2020

Naučno-praktičeskaâ revmatologiâ

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Autoimmune diseases, including rheumatoid arthritis (RA), are risk factors for thrombotic events. Understanding the pathogenetic role of hemostatic changes in RA can assist in developing measures for prevention, prognosis, early diagnosis, and treatment of immune thromboses. Objective: to investigate the state of platelet and plasma hemostasis in patients with RA, as compared to other laboratory parameters and clinical manifestations of the disease. Subjects and methods. Hemostasis was investigated using two relatively new laboratory tests: thrombodynamics and kinetics of blood clot contraction (BCC). Examinations were made in 60 patients with RA and in 50 apparently healthy individuals of the control group. Results and discussion. In patients with RA, the parameters of thrombodynamics and BCC were found to be significantly different from the normal values. According to thrombodynamics, there was an increase in plasma clot growth rate, size, and density, which indicates chronic hypercoagulation. The rate and completeness of BCC were substantially reduced due to platelet dysfunction in patients with RA compared to healthy individuals. The changes in the parameters of thrombodynamics and BCC correlated with the laboratory signs of systemic inflammation and depended on the radiographic stage of the disease. Conclusion. The results of this investigation confirm that hemostatic disorders are present in RA and indicate the informative value of thrombodynamics and BCC tests as indicators of a pre-thrombotic state, including autoimmune pathology.

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“…Platelet activation via FcγRIIa engagement occurs mostly by anti‐citrullinated protein Abs, 202 which are highly specific for RA and predictive of the onset of symptoms 205 . Platelet activation is increased in RA patients presenting these Abs 202,206 . Exposure to plasma from these patients activate platelets ex vivo, which is prevented by neutralizing Abs against FcγRIIa, 202 supporting participation of immune complexes and FcγRIIa in platelet activation during RA 202 …”

Section: Platelet Innate Immune Receptors In Sterile Inflammationmentioning

confidence: 94%

Innate immune receptors in platelets and platelet-leukocyte interactions

Dib

Quirino-Teixeira

Merij

et al. 2020

Journal of Leukocyte Biology

111

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Platelets are chief cells in hemostasis. Apart from their hemostatic roles, platelets are major inflammatory effector cells that can influence both innate and adaptive immune responses. Activated platelets have thromboinflammatory functions linking hemostatic and immune responses in several physiological and pathological conditions. Among many ways in which platelets exert these functions, platelet expression of pattern recognition receptors (PRRs), including TLR, Nod-like receptor, and C-type lectin receptor families, plays major roles in sensing and responding to pathogen-associated or damage-associated molecular patterns (PAMPs and DAMPs, respectively). In this review, an increasing body of evidence is compiled showing the participation of platelet innate immune receptors, including PRRs, in infectious diseases, sterile inflammation, and cancer. How platelet recognition of endogenous DAMPs participates in sterile inflammatory diseases and thrombosis is discussed. In addition, platelet recognition of both PAMPs and DAMPs initiates platelet-mediated inflammation and vascular thrombosis in infectious diseases, including viral, bacterial, and parasite infections. The study also focuses on the involvement of innate immune receptors in platelet activation during cancer, and their contribution to tumor microenvironment development and metastasis. Finally, how innate immune receptors participate in platelet communication with leukocytes, modulating leukocyte-mediated inflammation and immune functions, is highlighted. These cell communication processes, including platelet-induced release of neutrophil extracellular traps, platelet Ag presentation to T-cells and platelet modulation of monocyte cytokine secretion are discussed in the context of infectious and sterile diseases of major concern in human health, including cardiovascular diseases, dengue, HIV infection, sepsis, and cancer.

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Soluble glycoprotein VI, a specific marker of platelet activation is increased in the plasma of subjects with seropositive rheumatoid arthritis

Cited by 15 publications

References 22 publications

Soluble GPVI is elevated in injured patients: shedding is mediated by fibrin activation of GPVI

Soluble GPVI is elevated in injured patients: shedding is mediated by fibrin activation of GPVI

Changes in the Parameters of Thrombodynamics and Blood Clot Contraction in Patients With Rheumatoid Arthritis

Innate immune receptors in platelets and platelet-leukocyte interactions

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