Modifiers of complement activation for prevention of antibody-mediated injury to allografts

Hughes, Peter; Cohney, Solomon

doi:10.1097/mot.0b013e3283489a5a

Cited by 26 publications

(19 citation statements)

References 113 publications

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“…Complement activation by DSAs also has the potential to enhance alloantigen presentation to T cells by increasing CD40/CD40L expression and IL-12 production. Antibody production by antigen-specific B cells is also enhanced by C3a/C5a [15,16]. DSAs can bind to endothelial cell targets and stimulate cell proliferation or induce antibodydependent cell-mediated cytotoxicity (ADCC) with γ-IFN release.…”

Section: B Cells Donor-specific Antibodies and Complement As Mediatorsmentioning

confidence: 99%

“…Other, more specific, inhibitors of complement (Eculizumab ® , anti-C5, Alexion Pharmaceuticals, Cheshire, UK, CT.) and inhibitors of C1 (C1INH) may be useful in the prevention and treatment of ABMR, both in the acute and chronic phase. Trials of complement inhibitors in human kidney transplant recipients are now underway (NCT01327573, NCT01147302, NCT01134510) [15,16].…”

Section: B Cells Donor-specific Antibodies and Complement As Mediatorsmentioning

confidence: 99%

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Advancing kidney transplantation

Jordan

2012

Expert Review of Clinical Immunology

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Section: B Cells Donor-specific Antibodies and Complement As Mediatorsmentioning

confidence: 99%

Section: B Cells Donor-specific Antibodies and Complement As Mediatorsmentioning

confidence: 99%

Advancing kidney transplantation

Jordan

2012

Expert Review of Clinical Immunology

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“…With regards to the expression and pathology of AbMR, the potential for important interactions between pathways governing humoral immunity, coagulation, complement, complement regulatory proteins and other constitutive endothelial protective mechanisms has been noted (3,19). Phenotypic variations/abnormalities in these pathways may alter the pathogenicity of alloantibody, potentially lowering the threshold that triggers AbMR as described in a patient with a factor H mutation (10).…”

Section: To the Editormentioning

confidence: 99%

“…In the case of plasmapheresis (cf. immunoabsorption), this has the added advantage of removing complement (the other key player in AbMR), and a contributor to other transplant-related pathologies (19 …”

Section: To the Editormentioning

confidence: 99%

ABOi With Conventional Immunosuppression Alone–Antiblood Group Antibody Isn’t the Only Contributor to Antibody-Mediated Rejection and/or Thrombotic Microangiopathy

Cohney

Masterson

Hogan

et al. 2015

American Journal of Transplantation

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“…In transplantation medicine, complement activity is known to critically contribute to inflammation and the accommodation or rejection of transplanted tissue (Asgari et al 2010;Hughes and Cohney 2011). Complement inhibitors have been utilized in transplant recipients through various means to reduce the occurrence of adverse events against transplanted tissues, with mRCAs and C3 (or C3 convertases) being the most common points of intervention (Fig.…”

Section: Emerging Disease Areas Drive New Patent Applicationsmentioning

confidence: 99%

Complement in action: An analysis of patent trends from 1976 through 2011

DeAngelis

Yang

Reed³

et al. 2012

Immunobiology

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Complement is an essential part of the innate immune response. It interacts with diverse endogenous pathways and contributes to the maintenance of homeostasis, the modulation of adaptive immune responses, and the development of various pathologies. The potential usefulness, in both research and clinical settings, of compounds that detect or modulate complement activity has resulted in thousands of publications on complement-related innovations in fields such as drug discovery, disease diagnosis and treatment, and immunoassays, among others. This study highlights the distribution and publication trends of patents related to the complement system that were granted by the United States Patent and Trademark Office from 1976 to the present day. A comparison to complement-related documents published by the World Intellectual Property Organization is also included. Statistical analyses revealed increasing diversity in complementrelated research interests over time. More than half of the patents were found to focus on the discovery of inhibitors; interest in various inhibitor classes exhibited a remarkable transformation from chemical compounds early on to proteins and antibodies in more recent years. Among clinical applications, complement proteins and their modulators have been extensively patented for the diagnosis and treatment of eye diseases (especially age-related macular degeneration), graft rejection, cancer, sepsis, and a variety of other inflammatory and immune diseases. All of the patents discussed in this chapter, as well as those from other databases, are available from our newly constructed complement patent database: www.innateimmunity.us/patent. Complement in Infection and DiseaseBecause of the essential role of complement in the defense of the host against intruders, decreased activation of the complement system or deficiency in complement components can increase the risk of infection and cause various pathological conditions (Skattum et al. 2011). For example, alcoholic cirrhosis patients with low serum C3 concentrations and decreased hemolytic complement activity have been reported to have an increased risk of infections (Homann et al. 1997). Deficiencies of components of the classical pathway such as C1q, C2, and C4 have been found to be strongly associated with systemic lupus erythematosus (SLE) (Pickering et al. 2000;Pettigrew et al. 2009). On the other hand, uncontrolled, inappropriate, or excessive complement activity can cause damage to host cells and give rise to many diseases ranging from autoimmune to inflammatory pathologies (Markiewski and Lambris 2007;Holers 2003;Ricklin and Lambris 2007; Lambris and Sahu 2001). Indeed, the dual role of complement is illustrated by several pathological conditions. For example, the early increase of complement activation during sepsis may relate to the beneficial opsonization of bacteria. However, complement activation during subsequent phases of sepsis can amplify the initial insult, leading to inflammatory activity, tissue injury, and finally t...

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Modifiers of complement activation for prevention of antibody-mediated injury to allografts

Cited by 26 publications

References 113 publications

Advancing kidney transplantation

Advancing kidney transplantation

ABOi With Conventional Immunosuppression Alone–Antiblood Group Antibody Isn’t the Only Contributor to Antibody-Mediated Rejection and/or Thrombotic Microangiopathy

Complement in action: An analysis of patent trends from 1976 through 2011

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