The Pathogenesis of Systemic Lupus Erythematosus

Childs, Sharon G.

doi:10.1097/00006416-200603000-00013

Cited by 9 publications

(12 citation statements)

References 3 publications

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“…Immune complex deposition into cells and tissues precipitates inflammation, particularly of endothelial cells, leading to vasculitis, vasculopathy, and eventual organ damage. 48…”

Section: Systemic Lupus Erythematosusmentioning

confidence: 99%

Thrombosis in Systemic Lupus Erythematosus: Role of Impaired Fibrinolysis

Dhillon

Adams

2013

Semin Thromb Hemost

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Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that can affect any part of the body, including the skin, liver, kidneys, and blood. Thrombosis is a frequent manifestation in SLE, contributing significantly to patient morbidity and mortality, although the precise mechanism(s) of how this occurs remains unclear. Fibrinolysis is the physiologic process of thrombus digestion and provides an important balance to hemostasis. This process is triggered upon vessel injury with the release of tissue-type plasminogen activator (t-PA) from endothelial cells. The central component of the fibrinolytic pathway is plasminogen, a zymogen that is converted to plasmin by t-PA. Plasminogen/plasmin is absorbed into the developing thrombus and digests fibrinogen and fibrin within the hemostatic plug to prevent excessive clot formation. Abnormalities of the fibrinolytic pathway are associated either with the development of thrombosis (impaired fibrinolysis) or, to a lesser extent, bleeding (excessive fibrinolysis). Indeed, impaired fibrinolysis has been reported in patients with SLE and may contribute to both the development of hypercoagulability and an increased risk of thrombosis. Here we discuss the role of impaired fibrinolysis and its contribution to hypercoagulability and thrombosis in SLE.

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“…Immune complex deposition into cells and tissues precipitates inflammation, particularly of endothelial cells, leading to vasculitis, vasculopathy, and eventual organ damage. 48…”

Section: Systemic Lupus Erythematosusmentioning

confidence: 99%

Thrombosis in Systemic Lupus Erythematosus: Role of Impaired Fibrinolysis

Dhillon

Adams

2013

Semin Thromb Hemost

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“…Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory autoimmune disease that can affect almost any organ and can present with musculoskeletal, neuropsychiatric, renal, cutaneous, and hematologic manifestations alone or in combination [1–3]. …”

Section: Introductionmentioning

confidence: 99%

Adverse Event Burden, Resource Use, and Costs Associated with Immunosuppressant Medications for the Treatment of Systemic Lupus Erythematosus: A Systematic Literature Review

Oglesby

Shaul²,

Pokora³

et al. 2013

International Journal of Rheumatology

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This paper assessed the burden of adverse events (AEs) associated with azathioprine (AZA), cyclophosphamide (CYC), mycophenolate mofetil (MMF), methotrexate (MTX), and cyclosporine (CsA) in patients with systemic lupus erythematosus (SLE). Thirty-eight publications were included. Incidence of AEs ranged from 42.8% to 97.3%. Common AEs included infections (2.4–77%), gastrointestinal AEs (3.2–66.7%), and amenorrhea and/or ovarian complications (0–71%). More hematological cytopenias were associated with AZA (14 episodes) than MMF (2 episodes). CYC was associated with more infections than MMF (40–77% versus 12.5–32%, resp.) or AZA (17–77% versus 11–29%, resp.). Rates of hospitalized infections were similar between MMF and AZA patients, but higher for those taking CYC. There were more gynecological toxicities with CYC than MMF (32–36% versus 3.6–6%, resp.) or AZA (32–71% versus 8–18%, resp.). Discontinuation rates due to AEs were 0–44.4% across these medications. In summary, the incidence of AEs associated with SLE immunosuppressants was consistently high as reported in the literature; discontinuations due to these AEs were similar across treatments. Studies on the economic impact of these AEs were sparse and warrant further study. This paper highlights the need for more treatment options with better safety profiles.

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“…A note of concern is the possibility for side effects because of the complexation. It is known that immune complex deposition is a prominent feature of several autoimmune diseases such as the systemic lupus erythematosus (28). However, the serum concentration of IGF-II is relatively low leading to a relatively low rate of their formation so such possibility seems unlikely.…”

Section: Discussionmentioning

confidence: 99%

Human Monoclonal Antibodies Targeting Nonoverlapping Epitopes on Insulin-like Growth Factor II as a Novel Type of Candidate Cancer Therapeutics

Chen

Yang

Zhao

et al. 2012

Molecular Cancer Therapeutics

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Soluble ligands are important targets for therapy of cancers and other diseases. Therapeutic monoclonal antibodies (mAb) against such ligands block their interactions with corresponding receptors but do not enhance their removal from the circulation and can increase their half-lives because of the long half-lives of the antibodies. We have hypothesized that mAbs targeting two or more nonoverlapping epitopes on the same ligand could form oligomeric antibody-ligand complexes that can bind to cells expressing Fc gamma receptors (FcgRs) with high avidity leading to their fast and irreversible removal from the circulation. Insulin-like growth factor II (IGF-II) is an example of such ligands and an important target for human cancer therapy. We identified two mAbs, m610.27 and m630.3, which bound to nonoverlapping epitopes on IGF-II with nanomolar affinity, and generated a bispecific antibody, m660. m660 inhibited the interaction of human IGF-II (hIGF-II) with the human breast cancer cell line MCF-7, hIGF-II-mediated IGF receptor type I and insulin receptor phosphorylation, and cell growth. In the presence of hIGF-II, large complexes of m660 were formed that bound to FcgRIIexpressing BJAB cells much more efficiently than the monospecific antibody-hIGF-II complexes and were presumably phagocytosed by phorbol 12-myristate 13-acetate-stimulated macrophage-like U937 cells. A mixture of m610.27 and m630.3 exhibited similar properties. To our knowledge, these mAbs are the first reported to target nonoverlapping epitopes on a cancer-related ligand and could represent a novel class of candidate therapeutics against cancers. This approach could also be used to irreversibly eliminate other disease-related soluble ligands.

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The Pathogenesis of Systemic Lupus Erythematosus

Cited by 9 publications

References 3 publications

Thrombosis in Systemic Lupus Erythematosus: Role of Impaired Fibrinolysis

Thrombosis in Systemic Lupus Erythematosus: Role of Impaired Fibrinolysis

Adverse Event Burden, Resource Use, and Costs Associated with Immunosuppressant Medications for the Treatment of Systemic Lupus Erythematosus: A Systematic Literature Review

Human Monoclonal Antibodies Targeting Nonoverlapping Epitopes on Insulin-like Growth Factor II as a Novel Type of Candidate Cancer Therapeutics

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