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Article ; Online: B Cells in Systemic Lupus Erythematosus: From Disease Mechanisms to Targeted Therapies.

Canny, Susan P / Jackson, Shaun W

Rheumatic diseases clinics of North America

2021 Volume 47, Issue 3, Page(s) 395–413

Abstract: B cells exert a prominent contribution to the pathogenesis of systemic lupus erythematosus (SLE). Here, we review the immune mechanisms underlying autoreactive B cell activation in SLE, focusing on how B cell receptor and Toll-like receptor signals ... ...

Abstract	B cells exert a prominent contribution to the pathogenesis of systemic lupus erythematosus (SLE). Here, we review the immune mechanisms underlying autoreactive B cell activation in SLE, focusing on how B cell receptor and Toll-like receptor signals integrate to drive breaks in tolerance to nuclear antigens. In addition, we discuss autoantibody-dependent and autoantibody-independent B cell effector functions during lupus pathogenesis. Finally, we address efforts to target B cells therapeutically in human SLE. Despite initial disappointing clinical trials testing B cell depletion in lupus, more recent studies show promise, emphasizing how greater understanding of underlying immune mechanisms can yield clinical benefits.
MeSH term(s)	Autoantibodies ; B-Lymphocytes ; Humans ; Lupus Erythematosus, Systemic/drug therapy
Chemical Substances	Autoantibodies
Language	English
Publishing date	2021-06-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	92118-x
ISSN	1558-3163 ; 0889-857X
ISSN (online)	1558-3163
ISSN	0889-857X
DOI	10.1016/j.rdc.2021.04.006
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Article ; Online: Megakaryocyte buds are distinct from microvesicles and likely to represent platelet precursors.

Ellis, Marc L / Alwis, Imala / Smythe, Rhyll / Yuan, Yuping / Jackson, Shaun P

Blood advances

2022 Volume 7, Issue 6, Page(s) 982–986

MeSH term(s)	Megakaryocytes ; Blood Platelets ; Platelet Count
Language	English
Publishing date	2022-11-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2022008850
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Article ; Online: Impact of out-of-pocket costs on patient initiation, adherence and persistence rates for patients treated with anti-vascular endothelial growth factor medicines.

Jackson, Shaun / Stokes, John P

Clinical & experimental ophthalmology

2020 Volume 48, Issue 4, Page(s) 477–485

Abstract: Importance: Out-of-pocket costs are a key driver of patient decisions to access, adhere and persist with anti-vascular endothelial growth factor (VEGF) therapy. The Medicare Benefits Schedule Review Taskforce proposes a 69% reduction in the scheduled ... ...

Abstract	Importance: Out-of-pocket costs are a key driver of patient decisions to access, adhere and persist with anti-vascular endothelial growth factor (VEGF) therapy. The Medicare Benefits Schedule Review Taskforce proposes a 69% reduction in the scheduled fee for intravitreal injections (item 42 738) which risks increasing out-of-pocket costs for patients and worsening visual outcomes. Background: To determine the impact of out-of-pocket costs on current anti-VEGF utilization rates in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO). Design: This is a retrospective cohort drug-utilization analysis. Participants: This study involved 11 592 patients in Australia diagnosed with nAMD or DMO. Methods: A retrospective analysis of electronic, de-identified dispensing records of patients diagnosed with nAMD or DMO who initiated anti-VEGF therapy between January 1, 2016 and December 2018 across Australia. Patients were categorized by treatment facility type: bulk-billing clinics (BBCs) and "rest of market" clinics (ROMCs). Main outcome measures: Dispensing quantities, intervals and persistence rates. Results: For patients with nAMD who initiated therapy between 2016 and 2018 the mean number of medicines dispensed up to September 30, 2019 was 17.0 for BBC and 13.8 for ROMC patients. For patients with DMO, the mean number of medicines dispensed was 16.5 for BBC patients and 12.5 for ROMC patients. Patients treated at BBCs had higher persistence rates than those treated at ROMCs. DMO patients had higher initiation rates BBCs (46%) vs ROMCs (25%). Conclusions and relevance: Lower out-of-pocket costs are associated with higher adherence and persistence rates for anti-VEGF therapy in patients with AMD and DMO and higher initiation rates for DMO patients.
MeSH term(s)	Aged ; Angiogenesis Inhibitors/therapeutic use ; Bevacizumab ; Health Expenditures ; Humans ; Intravitreal Injections ; Medicare ; Ranibizumab ; Receptors, Vascular Endothelial Growth Factor ; Retrospective Studies ; United States ; Vascular Endothelial Growth Factor A
Chemical Substances	Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A ; Bevacizumab (2S9ZZM9Q9V) ; Receptors, Vascular Endothelial Growth Factor (EC 2.7.10.1) ; Ranibizumab (ZL1R02VT79)
Language	English
Publishing date	2020-01-13
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2014008-3
ISSN	1442-9071 ; 1442-6404
ISSN (online)	1442-9071
ISSN	1442-6404
DOI	10.1111/ceo.13706
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Article: Integrating Phenotypic and Chemoproteomic Approaches to Identify Covalent Targets of Dietary Electrophiles in Platelets.

Guan, Ivy A / Liu, Joanna S T / Sawyer, Renata C / Li, Xiang / Jiao, Wanting / Jiramongkol, Yannasittha / White, Mark D / Hagimola, Lejla / Passam, Freda H / Tran, Denise P / Liu, Xiaoming / Schoenwaelder, Simone M / Jackson, Shaun P / Payne, Richard J / Liu, Xuyu

ACS central science

2024 Volume 10, Issue 2, Page(s) 344–357

Abstract: A large variety of dietary phytochemicals has been shown to improve thrombosis and stroke outcomes in preclinical studies. Many of these compounds feature electrophilic functionalities that potentially undergo covalent addition to the sulfhydryl side ... ...

Abstract	A large variety of dietary phytochemicals has been shown to improve thrombosis and stroke outcomes in preclinical studies. Many of these compounds feature electrophilic functionalities that potentially undergo covalent addition to the sulfhydryl side chain of cysteine residues within proteins. However, the impact of such covalent modifications on the platelet activity and function remains unclear. This study explores the irreversible engagement of 23 electrophilic phytochemicals with platelets, unveiling the unique antiplatelet selectivity of sulforaphane (SFN). SFN impairs platelet responses to adenosine diphosphate (ADP) and a thromboxane A2 receptor agonist while not affecting thrombin and collagen-related peptide activation. It also substantially reduces platelet thrombus formation under arterial flow conditions. Using an alkyne-integrated probe, protein disulfide isomerase A6 (PDIA6) was identified as a rapid kinetic responder to SFN. Mechanistic profiling studies revealed SFN's nuanced modulation of PDIA6 activity and substrate specificity. In an electrolytic injury model of thrombosis, SFN enhanced the thrombolytic activity of recombinant tissue plasminogen activator (rtPA) without increasing blood loss. Our results serve as a catalyst for further investigations into the preventive and therapeutic mechanisms of dietary antiplatelets, aiming to enhance the clot-busting power of rtPA, currently the only approved therapeutic for stroke recanalization that has significant limitations.
Language	English
Publishing date	2024-01-29
Publishing country	United States
Document type	Journal Article
ISSN	2374-7943
ISSN	2374-7943
DOI	10.1021/acscentsci.3c00822
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Article ; Online: Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms.

Jackson, Shaun P / Darbousset, Roxane / Schoenwaelder, Simone M

Blood

2019 Volume 133, Issue 9, Page(s) 906–918

Abstract: Thrombosis with associated inflammation (thromboinflammation) occurs commonly in a broad range of human disorders. It is well recognized clinically in the context of superficial thrombophlebitis (thrombosis and inflammation of superficial veins); however, ...

Abstract	Thrombosis with associated inflammation (thromboinflammation) occurs commonly in a broad range of human disorders. It is well recognized clinically in the context of superficial thrombophlebitis (thrombosis and inflammation of superficial veins); however, it is more dangerous when it develops in the microvasculature of injured tissues and organs. Microvascular thrombosis with associated inflammation is well recognized in the context of sepsis and ischemia-reperfusion injury; however, it also occurs in organ transplant rejection, major trauma, severe burns, the antiphospholipid syndrome, preeclampsia, sickle cell disease, and biomaterial-induced thromboinflammation. Central to thromboinflammation is the loss of the normal antithrombotic and anti-inflammatory functions of endothelial cells, leading to dysregulation of coagulation, complement, platelet activation, and leukocyte recruitment in the microvasculature. α-Thrombin plays a critical role in coordinating thrombotic and inflammatory responses and has long been considered an attractive therapeutic target to reduce thromboinflammatory complications. This review focuses on the role of basic aspects of coagulation and α-thrombin in promoting thromboinflammatory responses and discusses insights gained from clinical trials on the effects of various inhibitors of coagulation on thromboinflammatory disorders. Studies in sepsis patients have been particularly informative because, despite using anticoagulant approaches with different pharmacological profiles, which act at distinct points in the coagulation cascade, bleeding complications continue to undermine clinical benefit. Future advances may require the development of therapeutics with primary anti-inflammatory and cytoprotective properties, which have less impact on hemostasis. This may be possible with the growing recognition that components of blood coagulation and platelets have prothrombotic and proinflammatory functions independent of their hemostatic effects.
MeSH term(s)	Anticoagulants/therapeutic use ; Blood Coagulation/drug effects ; Humans ; Inflammation/complications ; Inflammation/immunology ; Inflammation/prevention & control ; Thrombosis/complications ; Thrombosis/immunology ; Thrombosis/prevention & control
Chemical Substances	Anticoagulants
Language	English
Publishing date	2019-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2018-11-882993
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Article ; Online: Arterial thrombosis--insidious, unpredictable and deadly.

Jackson, Shaun P

Nature medicine

2011 Volume 17, Issue 11, Page(s) 1423–1436

Abstract: The formation of blood clots--thrombosis--at sites of atherosclerotic plaque rupture is a major clinical problem despite ongoing improvements in antithrombotic therapy. Progress in identifying the pathogenic mechanisms regulating arterial thrombosis has ... ...

Abstract	The formation of blood clots--thrombosis--at sites of atherosclerotic plaque rupture is a major clinical problem despite ongoing improvements in antithrombotic therapy. Progress in identifying the pathogenic mechanisms regulating arterial thrombosis has led to the development of newer therapeutics, and there is general anticipation that these treatments will have greater efficacy and improved safety. However, major advances in this field require the identification of specific risk factors for arterial thrombosis in affected individuals and a rethink of the 'one size fits all' approach to antithrombotic therapy.
MeSH term(s)	Acute Coronary Syndrome/etiology ; Acute Coronary Syndrome/pathology ; Animals ; Arteries/pathology ; Atherosclerosis/complications ; Atherosclerosis/pathology ; Blood Platelets/physiology ; Fibrin/metabolism ; Fibrinolytic Agents/therapeutic use ; Hemostasis ; Humans ; Plaque, Atherosclerotic/complications ; Plaque, Atherosclerotic/pathology ; Thrombin/metabolism ; Thrombosis/drug therapy ; Thrombosis/etiology ; Thrombosis/pathology
Chemical Substances	Fibrinolytic Agents ; Fibrin (9001-31-4) ; Thrombin (EC 3.4.21.5)
Language	English
Publishing date	2011-11-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/nm.2515
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Zs.A 4212: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Ferric chloride thrombosis model: unraveling the vascular effects of a highly corrosive oxidant.

Schoenwaelder, Simone M / Jackson, Shaun P

Blood

2015 Volume 126, Issue 24, Page(s) 2652–2653

MeSH term(s)	Animals ; Caustics/toxicity ; Chlorides/toxicity ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Endothelium, Vascular/drug effects ; Erythrocyte Aggregation/drug effects ; Erythrocytes/drug effects ; Ferric Compounds/toxicity ; Mice ; Oxidants/pharmacology ; Oxidants/toxicity ; Platelet Activation ; Thrombosis/chemically induced ; Thrombosis/prevention & control
Chemical Substances	Caustics ; Chlorides ; Ferric Compounds ; Oxidants ; ferric chloride (U38V3ZVV3V)
Language	English
Publishing date	2015-10-26
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2015-09-668384
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Article: Paraneoplastic bullous pemphigoid - A sign of clear cell renal carcinoma.

Jackson, Stuart R / Koestenbauer, Jakob / Carroll, Adam P / Oo, Than-Htike / Chou, Shaun / Indrajit, Balasubramaniam

Urology case reports

2020 Volume 30, Page(s) 101119

Abstract: Paraneoplastic bullous pemphigoid is a rare paraneoplastic syndrome. Rash is pruritic, with erythematous eruption of large subepidermal bullae over skin and often mucosal surfaces. We present an 84y woman with a three week history of erythematous rash, ... ...

Abstract	Paraneoplastic bullous pemphigoid is a rare paraneoplastic syndrome. Rash is pruritic, with erythematous eruption of large subepidermal bullae over skin and often mucosal surfaces. We present an 84y woman with a three week history of erythematous rash, and 48hrs of bullae. A left clear cell renal cell carcinoma was identified on CT imaging during the presentation. Subsequent removal of the tumour resulted in resolution of bullous pemphigoid symptoms. This first-of-kind case and successful result strengthens the association between renal cell carcinoma and paraneoplastic bullous pemphigoid, arguing for a high degree of clinical suspicion in unexplained presentations of bullous pemphigoid.
Language	English
Publishing date	2020-01-13
Publishing country	United States
Document type	Case Reports
ZDB-ID	2745459-9
ISSN	2214-4420
ISSN	2214-4420
DOI	10.1016/j.eucr.2020.101119
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Article ; Online: Development of a carotid artery thrombolysis stroke model in mice.

Maclean, Jessica A A / Tomkins, Amelia J / Sturgeon, Sharelle A / Hofma, Benjamin R / Alwis, Imala / Samson, Andre L / Schoenwaelder, Simone M / Jackson, Shaun P

Blood advances

2022 Volume 6, Issue 18, Page(s) 5449–5462

Abstract: Recanalization with restored cerebral perfusion is the primary goal of thrombolytic therapy in acute ischemic stroke. The identification of adjunctive therapies that can be safely used to enhance thrombolysis in stroke remains an elusive goal. We report ... ...

Abstract	Recanalization with restored cerebral perfusion is the primary goal of thrombolytic therapy in acute ischemic stroke. The identification of adjunctive therapies that can be safely used to enhance thrombolysis in stroke remains an elusive goal. We report here the development of a mouse in situ carotid artery thrombolysis (iCAT) stroke model involving graded cerebral ischemia to induce unihemispheric infarction after thrombotic occlusion of the common carotid artery (CCA). Electrolytic-induced thrombotic occlusion of the left CCA enabled real-time assessment of recanalization and rethrombosis events after thrombolysis with recombinant tissue-type plasminogen activator (rtPA). Concurrent transient stenosis of the right CCA induced unihemispheric hypoperfusion and infarction in the left middle cerebral artery territory. Real-time assessment of thrombolysis revealed recanalization rates <30% in rtPA-treated animals with high rates of rethrombosis. Addition of the direct thrombin inhibitor argatroban increased recanalization rates to 50% and reduced rethrombosis. Paradoxically, this was associated with increased cerebral ischemia and stroke-related mortality (25%-42%). Serial analysis of carotid and cerebral blood flow showed that coadministration of argatroban with rtPA resulted in a marked increase in carotid artery embolization, leading to distal obstruction of the middle cerebral artery. Real-time imaging of carotid thrombi revealed that adjunctive anticoagulation destabilized platelet-rich thrombi at the vessel wall, leading to dislodgement of large platelet emboli. These studies confirm the benefits of anticoagulants in enhancing thrombolysis and large artery recanalization; however, at high levels of anticoagulation (∼3-fold prolongation of activated partial thromboplastin time), this effect is offset by increased incidence of carotid artery embolization and distal middle cerebral artery occlusion. The iCAT stroke model should provide important new insight into the effects of adjunctive antithrombotic agents on real-time thrombus dynamics during thrombolysis and their correlation with stroke outcomes.
MeSH term(s)	Animals ; Anticoagulants/therapeutic use ; Antithrombins/therapeutic use ; Arginine/analogs & derivatives ; Brain Ischemia/complications ; Brain Ischemia/drug therapy ; Carotid Artery, Common ; Fibrinolytic Agents/pharmacology ; Fibrinolytic Agents/therapeutic use ; Infarction, Middle Cerebral Artery/complications ; Infarction, Middle Cerebral Artery/drug therapy ; Ischemic Stroke ; Mice ; Pipecolic Acids ; Stroke/drug therapy ; Stroke/etiology ; Sulfonamides ; Thromboembolism ; Thrombolytic Therapy/adverse effects ; Thrombolytic Therapy/methods ; Tissue Plasminogen Activator/pharmacology ; Tissue Plasminogen Activator/therapeutic use ; Treatment Outcome
Chemical Substances	Anticoagulants ; Antithrombins ; Fibrinolytic Agents ; Pipecolic Acids ; Sulfonamides ; Arginine (94ZLA3W45F) ; Tissue Plasminogen Activator (EC 3.4.21.68) ; argatroban (IY90U61Z3S)
Language	English
Publishing date	2022-06-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2021006008
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Article ; Online: SR-BI and fatty platelets.

Kaplan, Zane S / Jackson, Shaun P

Blood

2010 Volume 116, Issue 11, Page(s) 1827–1828

Language	English
Publishing date	2010-09-16
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2010-06-289827
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