Protein therapeutics and their lessons: Expect the unexpected when inhibiting the multi‐protein cascade of the complement system

Upregulation of Checkpoint Ligand Programmed Death-Ligand 1 in Patients with Paroxysmal Nocturnal Hemoglobinuria Explained by Proximal Complement Activation

(2022) Markus Anliker et al.   JOURNAL OF IMMUNOLOGY

Compstatins: the dawn of clinical C3-targeted complement inhibition

(2022) Christina Lamers et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Factor H Autoantibodies and Complement-Mediated Diseases

(2021) Yuzhou Zhang et al.   Frontiers in Immunology

Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria

(2021) Peter Hillmen et al.   NEW ENGLAND JOURNAL OF MEDICINE

Sutimlimab in Cold Agglutinin Disease

(2021) Alexander Röth et al.   NEW ENGLAND JOURNAL OF MEDICINE

Complement Blockade in Recipients Prevents Delayed Graft Function and Delays Antibody-mediated Rejection in a Nonhuman Primate Model of Kidney Transplantation

(2021) Michael J. Eerhart et al.   TRANSPLANTATION

Potent preclinical activity of HexaBody-DR5/DR5 in relapsed and/or refractory multiple myeloma

(2021) Hilma J. van der Horst et al.   Blood Advances

Complement and the prothrombotic state

(2021) Christoph Q Schmidt et al.   BLOOD

Tipping the balance: intricate roles of the complement system in disease and therapy

(2021) Richard B. Pouw et al.   Seminars in Immunopathology

Gain-of-Function Mutations R249C and S250C in Complement C2 Protein Increase C3 Deposition in the Presence of C-Reactive Protein

(2021) Aleksandra Urban et al.   Frontiers in Immunology

Homodimeric Minimal Factor H: In Vivo Tracking and Extended Dosing Studies in Factor H Deficient Mice

(2021) Ola Kamala et al.   Frontiers in Immunology

The complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria

(2020) Alexander Röth et al.   BLOOD

Long-term outcomes and response to treatment in diacylglycerol kinase epsilon nephropathy.

(2020) Vicky Brocklebank et al.   KIDNEY INTERNATIONAL

Microglia complement astrocytes in neuromyelitis optica

(2020) Zahra Moinfar et al.   JOURNAL OF CLINICAL INVESTIGATION

C3(H2O) prevents rescue of complement-mediated C3 glomerulopathy in Cfh–/– Cfd–/– mice

(2020) Yuzhou Zhang et al.   JCI Insight

Tuning the Functionality by Splicing: Factor H and Its Alternative Splice Variant FHL-1 Share a Gene but Not All Functions

(2020) Marco Mannes et al.   Frontiers in Immunology

Complement inhibition at the level of C3 or C5: mechanistic reasons for ongoing terminal pathway activity

(2020) Marco Mannes et al.   BLOOD

C3 glomerulopathy — understanding a rare complement-driven renal disease

(2019) Richard J. H. Smith et al.   Nature Reviews Nephrology

Differential contribution of C5aR and C5b-9 pathways to renal thrombic microangiopathy and macrovascular thrombosis in mice carrying an atypical hemolytic syndrome–related factor H mutation

(2019) Yoshiyasu Ueda et al.   KIDNEY INTERNATIONAL

Eculizumab in Aquaporin-4–Positive Neuromyelitis Optica Spectrum Disorder

(2019) Sean J. Pittock et al.   NEW ENGLAND JOURNAL OF MEDICINE

Complement C3 inhibition by compstatin Cp40 prevents intra- and extravascular hemolysis of red blood cells

(2019) Inge Baas et al.   HAEMATOLOGICA

Anti-complement Treatment for Paroxysmal Nocturnal Hemoglobinuria: Time for Proximal Complement Inhibition? A Position Paper From the SAAWP of the EBMT

(2019) Antonio M. Risitano et al.   Frontiers in Immunology

Different Levels of Incomplete Terminal Pathway Inhibition by Eculizumab and the Clinical Response of PNH Patients

(2019) Markus J. Harder et al.   Frontiers in Immunology

Investigational RNAi Therapeutic Targeting C5 Is Efficacious in Pre-clinical Models of Myasthenia Gravis

(2019) Linda L. Kusner et al.   Molecular Therapy-Methods & Clinical Development

Compendium of current complement therapeutics

(2019) Wioleta M Zelek et al.   MOLECULAR IMMUNOLOGY

An inhibitor of complement C5 provides structural insights into activation

(2019) Martin P. Reichhardt et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Toward complement inhibition 2.0: Next generation anticomplement agents for paroxysmal nocturnal hemoglobinuria

(2018) Antonio M. Risitano et al.   AMERICAN JOURNAL OF HEMATOLOGY

OUP accepted manuscript

(2018)   GLYCOBIOLOGY

Contribution of Adipose-Derived Factor D/Adipsin to Complement Alternative Pathway Activation: Lessons from Lipodystrophy

(2018) Xiaobo Wu et al.   JOURNAL OF IMMUNOLOGY

Statistical Validation of Rare Complement Variants Provides Insights into the Molecular Basis of Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy

(2018) Amy J. Osborne et al.   JOURNAL OF IMMUNOLOGY

Design and preclinical characterization of ALXN1210: A novel anti-C5 antibody with extended duration of action

(2018) Douglas Sheridan et al.   PLoS One

Efficacy and Safety of Lampalizumab for Geographic Atrophy Due to Age-Related Macular Degeneration

(2018) Frank G. Holz et al.   JAMA Ophthalmology

Functional Characterization of Alternative and Classical Pathway C3/C5 Convertase Activity and Inhibition Using Purified Models

(2018) Seline A. Zwarthoff et al.   Frontiers in Immunology

Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study

(2018) Austin G. Kulasekararaj et al.   BLOOD

Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study

(2018) Jong Wook Lee et al.   BLOOD

Complement activation by human red blood cell antibodies: hemolytic potential of antibodies and efficacy of complement inhibitors assessed by a sensitive flow cytometric assay

(2018) Markus Anliker et al.   TRANSFUSION

Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study

(2017) James F Howard et al.   LANCET NEUROLOGY

The renaissance of complement therapeutics

(2017) Daniel Ricklin et al.   Nature Reviews Nephrology

Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses

(2017) Xiaoguang Xue et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Targeting factor D of the alternative complement pathway reduces geographic atrophy progression secondary to age-related macular degeneration

(2017) Brian L. Yaspan et al.   Science Translational Medicine

The eye as a complement dysregulation hotspot

(2017) Simon J. Clark et al.   Seminars in Immunopathology

Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses

(2017) Xiaoguang Xue et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Long lasting neutralization of C5 by SKY59, a novel recycling antibody, is a potential therapy for complement-mediated diseases

(2017) Taku Fukuzawa et al.   Scientific Reports

Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment

(2016) Sacha Zeerleder et al.   ANNALS OF MEDICINE

PASylated Coversin, a C5-Specific Complement Inhibitor with Extended Pharmacokinetics, Shows Enhanced Anti-Hemolytic Activity in Vitro

(2016) Nadine Kuhn et al.   BIOCONJUGATE CHEMISTRY

Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation

(2016) Markus J. Harder et al.   BLOOD

Monitoring of complement activation biomarkers and eculizumab in complement-mediated renal disorders

(2016) C. Wehling et al.   CLINICAL AND EXPERIMENTAL IMMUNOLOGY

Selectivity of C3-opsonin targeted complement inhibitors: A distinct advantage in the protection of erythrocytes from paroxysmal nocturnal hemoglobinuria patients

(2016) Christoph Q. Schmidt et al.   IMMUNOBIOLOGY

The membrane attack complex as an inflammatory trigger

(2016) B. Paul Morgan   IMMUNOBIOLOGY

Protection of host cells by complement regulators

(2016) Christoph Q. Schmidt et al.   IMMUNOLOGICAL REVIEWS

Structural Basis for Eculizumab-Mediated Inhibition of the Complement Terminal Pathway

(2016) Janus Asbjørn Schatz-Jakobsen et al.   JOURNAL OF IMMUNOLOGY

Structural basis for therapeutic inhibition of complement C5

(2016) Matthijs M Jore et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Characterization of C3 in C3 glomerulopathy

(2016) Sanjeev Sethi et al.   NEPHROLOGY DIALYSIS TRANSPLANTATION

Complement C3 inhibitor Cp40 attenuates xenoreactions in pig hearts perfused with human blood

(2016) Jan-Michael Abicht et al.   XENOTRANSPLANTATION

Structural basis for therapeutic inhibition of complement C5

(2016) Matthijs M Jore et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Cold agglutinin disease

(2016) S. Berentsen   Hematology-American Society of Hematology Education Program

Dissecting complement blockade for clinic use

(2015) A. M. Risitano   BLOOD

Complement C3dg-mediated erythrophagocytosis: implications for paroxysmal nocturnal hemoglobinuria

(2015) Z. Lin et al.   BLOOD

Molecular insights into the surface-specific arrangement of complement C5 convertase enzymes

(2015) Evelien T. M. Berends et al.   BMC BIOLOGY

Compstatin: a C3-targeted complement inhibitor reaching its prime for bedside intervention

(2015) Dimitrios C. Mastellos et al.   EUROPEAN JOURNAL OF CLINICAL INVESTIGATION

Compstatin analog Cp40 inhibits complement dysregulation in vitro in C3 glomerulopathy

(2015) Yuzhou Zhang et al.   IMMUNOBIOLOGY

Anti–Factor H Autoantibodies in C3 Glomerulopathies and in Atypical Hemolytic Uremic Syndrome: One Target, Two Diseases

(2015) Caroline Blanc et al.   JOURNAL OF IMMUNOLOGY

Comparative Analysis of Novel Complement-Targeted Inhibitors, MiniFH, and the Natural Regulators Factor H and Factor H–like Protein 1 Reveal Functional Determinants of Complement Regulation

(2015) Markus J. Harder et al.   JOURNAL OF IMMUNOLOGY

An extended mini-complement factor H molecule ameliorates experimental C3 glomerulopathy

(2015) Eva-Maria Nichols et al.   KIDNEY INTERNATIONAL

More than just immune evasion: Hijacking complement by Plasmodium falciparum

(2015) Christoph Q. Schmidt et al.   MOLECULAR IMMUNOLOGY

Age-Related Macular Degeneration: Genetics and Biology Coming Together

(2014) Lars G. Fritsche et al.   Annual Review of Genomics and Human Genetics

Dynamics of complement activation in aHUS and how to monitor eculizumab therapy

(2014) M. Noris et al.   BLOOD

TNT003, an inhibitor of the serine protease C1s, prevents complement activation induced by cold agglutinins

(2014) J. Shi et al.   BLOOD

A novel method for direct measurement of complement convertases activity in human serum

(2014) A. M. Blom et al.   CLINICAL AND EXPERIMENTAL IMMUNOLOGY

Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry

(2014) H. Schrezenmeier et al.   HAEMATOLOGICA

A New Map of Glycosaminoglycan and C3b Binding Sites on Factor H

(2014) C. Q. Schmidt et al.   JOURNAL OF IMMUNOLOGY

Genetic variants in the complement system predisposing to age-related macular degeneration: A review

(2014) Elizabeth C. Schramm et al.   MOLECULAR IMMUNOLOGY

Complement Nomenclature 2014

(2014) Claudia Kemper et al.   MOLECULAR IMMUNOLOGY

Complement Is Activated by IgG Hexamers Assembled at the Cell Surface

(2014) C. A. Diebolder et al.   SCIENCE

Spectrum of Complement-Mediated Thrombotic Microangiopathies: Pathogenetic Insights Identifying Novel Treatment Approaches

(2014) Magdalena Riedl et al.   SEMINARS IN THROMBOSIS AND HEMOSTASIS

C1-Inhibitor protects from focal brain trauma in a cortical cryolesion mice model by reducing thrombo-inflammation

(2014) Christiane Albert-Weissenberger et al.   Frontiers in Cellular Neuroscience

IgG Subclasses and Allotypes: From Structure to Effector Functions

(2014) Gestur Vidarsson et al.   Frontiers in Immunology

Thrombosis in paroxysmal nocturnal hemoglobinuria

(2013) A. Hill et al.   BLOOD

Rational Engineering of a Minimized Immune Inhibitor with Unique Triple-Targeting Properties

(2013) C. Q. Schmidt et al.   JOURNAL OF IMMUNOLOGY

Pathogenic immune mechanisms at the neuromuscular synapse: the role of specific antibody-binding epitopes in myasthenia gravis

(2013) M. G. Huijbers et al.   JOURNAL OF INTERNAL MEDICINE

Soluble CR1 Therapy Improves Complement Regulation in C3 Glomerulopathy

(2013) Y. Zhang et al.   JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY

Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study

(2013) Sean J Pittock et al.   LANCET NEUROLOGY

A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis

(2013) James F. Howard et al.   MUSCLE & NERVE

Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome

(2013) Mathieu Lemaire et al.   NATURE GENETICS

Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic–Uremic Syndrome

(2013) C.M. Legendre et al.   NEW ENGLAND JOURNAL OF MEDICINE

Systemic Complement Inhibition with Eculizumab for Geographic Atrophy in Age-Related Macular Degeneration

(2013) Zohar Yehoshua et al.   OPHTHALMOLOGY

Structural insight on the recognition of surface-bound opsonins by the integrin I domain of complement receptor 3

(2013) G. Bajic et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Inhibiting Alternative Pathway Complement Activation by Targeting the Factor D Exosite

(2012) Kenneth J. Katschke et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The C5 Convertase Is Not Required for Activation of the Terminal Complement Pathway in Murine Experimental Cerebral Malaria

(2012) Theresa N. Ramos et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Increase of complement fragment C5a in cerebrospinal fluid during exacerbation of neuromyelitis optica

(2012) Hiroshi Kuroda et al.   JOURNAL OF NEUROIMMUNOLOGY

The complotype: dictating risk for inflammation and infection

(2012) Claire L. Harris et al.   TRENDS IN IMMUNOLOGY

Autoantibody-mediated arthritis in the absence of C3 and activating Fcγ receptors: C5 is activated by the coagulation cascade

(2012) Jennifer L Auger et al.   ARTHRITIS RESEARCH & THERAPY

Design and development of TT30, a novel C3d-targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases

(2011) M. Fridkis-Hareli et al.   BLOOD

Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival

(2011) R. J. Kelly et al.   BLOOD

Substrate recognition by complement convertases revealed in the C5-cobra venom factor complex

(2011) Nick S Laursen et al.   EMBO JOURNAL

Chemical labelling of active serum thioester proteins for quantification

(2011) Lotta Holm et al.   IMMUNOBIOLOGY

Neonatal Fc receptor and IgG-based therapeutics

(2011) Timothy T. Kuo et al.   mAbs

Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk

(2011) M. Heurich et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Paroxysmal nocturnal haemoglobinuria treatment with eculizumab is associated with a positive direct antiglobulin test

(2011) B. Höchsmann et al.   VOX SANGUINIS

Relative Role of Genetic Complement Abnormalities in Sporadic and Familial aHUS and Their Impact on Clinical Phenotype

(2010) M. Noris et al.   Clinical Journal of the American Society of Nephrology

Eculizumab prevents intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and unmasks low-level extravascular hemolysis occurring through C3 opsonization

(2010) A. Hill et al.   HAEMATOLOGICA

Complement Component C3 Binds to Activated Normal Platelets without Preceding Proteolytic Activation and Promotes Binding to Complement Receptor 1

(2010) Osama A. Hamad et al.   JOURNAL OF IMMUNOLOGY

Complement: a key system for immune surveillance and homeostasis

(2010) Daniel Ricklin et al.   NATURE IMMUNOLOGY

Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab

(2009) A. M. Risitano et al.   BLOOD

The Binding of Factor H to a Complex of Physiological Polyanions and C3b on Cells Is Impaired in Atypical Hemolytic Uremic Syndrome

(2009) V. P. Ferreira et al.   JOURNAL OF IMMUNOLOGY

Glomeruli of Dense Deposit Disease contain components of the alternative and terminal complement pathway

(2009) Sanjeev Sethi et al.   KIDNEY INTERNATIONAL

Structure of complement fragment C3b–factor H and implications for host protection by complement regulators

(2009) Jin Wu et al.   NATURE IMMUNOLOGY

Recurrent Atypical Hemolytic Uremic Syndrome Associated With Factor I Mutation in a Living Related Renal Transplant Recipient

(2008) Micah R. Chan et al.   AMERICAN JOURNAL OF KIDNEY DISEASES

The tick-over theory revisited: Formation and regulation of the soluble alternative complement C3 convertase (C3(H2O)Bb)

(2007) Fredrik Bexborn et al.   MOLECULAR IMMUNOLOGY