Search Our Scientific Publications & Authors

Front Immunol 2019 27;10:337. Epub 2019 Feb 27.

Division of Biodiagnostic Sciences and Technologies, INRASTES, National Center for Scientific Research Demokritos, Athens, Greece.

Thrombotic microangiopathies (TMAs) are a heterogeneous group of syndromes presenting with a distinct clinical triad: microangiopathic hemolytic anemia, thrombocytopenia, and organ damage. We currently recognize two major entities with distinct pathophysiology: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Beyond them, differential diagnosis also includes TMAs associated with underlying conditions, such as drugs, malignancy, infections, scleroderma-associated renal crisis, systemic lupus erythematosus (SLE), malignant hypertension, transplantation, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), and disseminated intravascular coagulation (DIC). Read More

Nat Rev Nephrol 2019 Mar;15(3):129-143

Molecular Otolaryngology and Renal Research Laboratories and the Departments of Internal Medicine and Pediatrics (Divisions of Nephrology), Carver College of Medicine, University of Iowa, Iowa City, IA, USA.

The C3 glomerulopathies are a group of rare kidney diseases characterized by complement dysregulation occurring in the fluid phase and in the glomerular microenvironment, which results in prominent complement C3 deposition in kidney biopsy samples. The two major subgroups of C3 glomerulopathy - dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) - have overlapping clinical and pathological features suggestive of a disease continuum. Dysregulation of the complement alternative pathway is fundamental to the manifestations of C3 glomerulopathy, although terminal pathway dysregulation is also common. Read More

J Alzheimers Dis Rep 2018 Dec 20;2(1):219-228. Epub 2018 Dec 20.

Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.

Our research into Alzheimer's disease (AD) focuses on the oral cavity and the brain, from which key evaluations of prospective and retrospective population-based data have shown that chronic periodontal disease existing for ten-years or over doubles the risk for the sporadic form of AD. Furthermore, () mono-infections in established periodontal lesions, or introducing its lipopolysachharide (LPS), as demonstrated in studies, show hallmark pathology inclusive of extracellular amyloid plaques and phospho-tau bound neurofibrillary tangles with AD-like phenotype. Other studies have shown that if periodontitis remains untreated in human AD patients, cognitive decline ensues. Read More

Front Immunol 2018 20;9:2664. Epub 2018 Nov 20.

Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.

The complement system is essential for an adequate immune response. Much attention has been given to the role of complement in disease. However, to better understand complement in pathology, it is crucial to first analyze this system under different physiological conditions. Read More

Front Immunol 2018 24;9:2237. Epub 2018 Oct 24.

Rudbeck Laboratory C5:3, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Complement system aberrations have been identified as pathophysiological mechanisms in a number of diseases and pathological conditions either directly or indirectly. Examples of such conditions include infections, inflammation, autoimmune disease, as well as allogeneic and xenogenic transplantation. Both prospective and retrospective studies have demonstrated significant complement-related differences between patient groups and controls. Read More

J Atheroscler Thromb 2019 Feb 2;26(2):99-110. Epub 2018 Nov 2.

Division of Nephrology and Endocrinology, the University of Tokyo Hospital.

Atypical hemolytic uremic syndrome (aHUS) is a type of thrombotic microangiopathy (TMA) defined by thrombocytopenia, microangiopathic hemolytic anemia, and renal failure. aHUS is caused by uncontrolled complement activation in the alternative pathway (AP). A variety of genetic defects in complement-related factors or acquired autoantibodies to the complement regulators have been found in 50 to 60% of all cases. Read More

World J Transplant 2018 Oct;8(6):203-219

Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom.

For decades, kidney diseases related to inappropriate complement activity, such as atypical hemolytic uremic syndrome and C3 glomerulopathy (a subtype of membranoproliferative glomerulonephritis), have mostly been complicated by worsened prognoses and rapid progression to end-stage renal failure. Alternative complement pathway dysregulation, whether congenital or acquired, is well-recognized as the main driver of the disease process in these patients. The list of triggers include: surgery, infection, immunologic factors, pregnancy and medications. Read More

Med Microbiol Immunol 2018 Oct 10. Epub 2018 Oct 10.

Laboratory of Microbiology, School of Medicine, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece.

Influenza remains an important threat for human health, despite the extensive study of influenza viruses and the production of effective vaccines. In contrast to virus genetics determinants, host genetic factors with clinical impact remained unexplored until recently. The association between three single nucleotide polymorphisms (SNPs) and influenza outcome in a European population was investigated in the present study. Read More

Pediatr Nephrol 2018 Aug 23. Epub 2018 Aug 23.

Radboud Institute for Molecular Life Sciences, Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Geert Grooteplein Zuid 10, PO Box 9101, 6525 GA, Nijmegen, The Netherlands.

Properdin is known as the only positive regulator of the complement system. Properdin promotes the activity of this defense system by stabilizing its key enzymatic complexes: the complement alternative pathway (AP) convertases. Besides, some studies have indicated a role for properdin as an initiator of complement activity. Read More

Front Immunol 2018 8;9:1851. Epub 2018 Aug 8.

Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.

The complement system has moved into the focus of drug development efforts in the last decade, since its inappropriate or uncontrolled activation has been recognized in many diseases. Some of them are primarily complement-mediated rare diseases, such as paroxysmal nocturnal hemoglobinuria, C3 glomerulonephritis, and atypical hemolytic uremic syndrome. Complement also plays a role in various multifactorial diseases that affect millions of people worldwide, such as ischemia reperfusion injury (myocardial infarction, stroke), age-related macular degeneration, and several neurodegenerative disorders. Read More

J Neuroinflammation 2018 May 14;15(1):141. Epub 2018 May 14.

Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL, 60612, USA.

Background: Microglial activation contributes to the neuropathology associated with chronic alcohol exposure and withdrawal, including the expression of inflammatory and anti-inflammatory genes. In the current study, we examined the transcriptome of primary rat microglial cells following incubation with alcohol alone, or alcohol together with a robust inflammatory stimulus.

Methods: Primary microglia were prepared from mixed rat glial cultures. Read More

Fish Shellfish Immunol 2018 Jun 30;77:214-221. Epub 2018 Mar 30.

School of Marine and Atmospheric Sciences, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address:

The hard clam (Mercenaria mercenaria) is among the most economically-important marine species along the east coast of the United States, representing the first marine resource in several Northeastern states. The species is rather resilient to infections and the only important disease of hard clams results from an infection caused by Quahog Parasite Unknown (QPX), a protistan parasite that can lead to significant mortality events in wild and aquacultured clam stocks. Though the presence of QPX disease has been documented since the 1960s, little information is available on cellular and molecular interactions between the parasite and the host. Read More

Curr Opin Nephrol Hypertens 2018 05;27(3):165-170

Department of Medicine, Imperial College London, London, UK.

Purpose Of Review: The current review will discuss recent advances in our understanding of the pathology of C3 glomerulopathy and atypical haemolytic uremic syndrome (aHUS).

Recent Findings: C3 glomerulopathy and aHUS are associated with abnormalities of control of the alternative pathway of complement. Recent articles have provided new insights into the classification of C3 glomerulopathy and its relationship to idiopathic immune complex-mediated glomerulonephritis. Read More

Clin Neurophysiol 2018 02 26;129(2):368-376. Epub 2017 Nov 26.

Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, United States. Electronic address:

Objective: To investigate cortical activity using scalp EEG in patients with isolated dystonia treated with chronic deep brain stimulation (DBS), on and off stimulation.

Methods: We analyzed 64-channel scalp EEG in 12 isolated dystonia patients treated with chronic DBS (7 generalized, 5 cervical/segmental; 7 globus pallidus (GP), 5 subthalamic nucleus (STN)), and 20 healthy age-matched controls. Recordings during rest and movement task, and clinical motor scores, were collected with DBS-on and during a 90-min DBS washout. Read More

J Infect Dis 2018 Mar;217(6):1000-1010

Tennessee Department of Health, Nashville.

Background: Postdiarrheal hemolytic-uremic syndrome (D+HUS) following Shiga toxin-producing Escherichia coli (STEC) infection is a serious condition lacking specific treatment. Host immune dysregulation and genetic susceptibility to complement hyperactivation are implicated in non-STEC-related HUS. However, genetic susceptibility to D+HUS remains largely uncharacterized. Read More

J Nephrol 2018 08 18;31(4):503-510. Epub 2017 Nov 18.

Department of Clinical and Molecular Medicine, University of Rome "La Sapienza", Rome, Italy.

Recently, a number of reports have described dominant C3 deposits in renal biopsies of patients with infection-related glomerulonephritis (GN). While acute post-infectious GN and membranoproliferative GN are commonly characterized by immune deposits containing C3 and/or C4, the absence of immunoglobulin (Ig) and/or immune complexes at light or electron microscopy is a rather unusual observation. Dominant C3 deposition is believed to result from the alternative pathway of complement activation via the C3bBb "tickover" convertase. Read More

Immunol Invest 2017 Nov;46(8):816-832

b Division of Nephrology , UB Clinical and Translational Research Center , Buffalo , NY , USA.

The complement system which is a critical mediator of innate immunity plays diverse roles in the neuropathogenesis of HIV-1 infection such as clearing HIV-1 and promoting productive HIV-1 replication. In the development of HIV-1 associated neurological disorders (HAND), there may be an imbalance between complement activation and regulation, which may contribute to the neuronal damage as a consequence of HIV-1 infection. It is well recognized that opiate abuse exacerbates HIV-1 neuropathology, however, little is known about the role of complement proteins in opiate induced neuromodulation, specifically in the presence of co-morbidity such as HIV-1 infection. Read More

Front Med (Lausanne) 2017 12;4:99. Epub 2017 Jul 12.

Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

The complement system is part of the innate immune response that plays important roles in protecting the host from foreign pathogens. The complement components and relative fragment deposition have long been recognized to be strongly involved also in the pathogenesis of autoantibody-related kidney glomerulopathies, leading to direct glomerular injury and recruitment of infiltrating inflammation pathways. More recently, unregulated complement activation has been shown to be associated with progression of non-antibody-mediated kidney diseases, including focal segmental glomerulosclerosis, C3 glomerular disease, thrombotic microangiopathies, or general fibrosis generation in progressive chronic kidney diseases. Read More

Dev Comp Immunol 2017 11 20;76:209-219. Epub 2017 Jun 20.

Liaoning Key Laboratory of Marine Animal Immunology & Disease Control, Dalian, 116023, China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071, China. Electronic address:

The complement system is one of the major effector mechanisms of immune system, playing essential roles in both the innate and adaptive immune responses. In the present study, the counterparts of vertebrate complement components were identified by screening the sequenced genome of Crassostrea gigas, resulting in the identification of 792 gene models containing complement-related domains. The transcriptome of haemocytes at 6, 12 and 24 h post lipopolysaccharides (LPS) stimulation showed differential expression of 77 C1q domain containing proteins, 53 C-type lectins and 42 fibrinogen-related proteins. Read More

Kidney Int 2017 10 19;92(4):953-963. Epub 2017 Jun 19.

Department of Cellular and Molecular Medicine and Center for Biological Research and Center for Biomedical Network Research on Rare Diseases, Madrid, Spain. Electronic address:

IgA nephropathy (IgAN), a frequent cause of chronic kidney disease worldwide, is characterized by mesangial deposition of galactose-deficient IgA1-containing immune complexes. Complement involvement in IgAN pathogenesis is suggested by the glomerular deposition of complement components and the strong protection from IgAN development conferred by the deletion of the CFHR3 and CFHR1 genes (Δ). Here we searched for correlations between clinical progression and levels of factor H (FH) and FH-related protein 1 (FHR-1) using well-characterized patient cohorts consisting of 112 patients with IgAN, 46 with non-complement-related autosomal dominant polycystic kidney disease (ADPKD), and 76 control individuals. Read More

Mol Immunol 2017 09 31;89:10-21. Epub 2017 May 31.

Department of Immunology, Oslo University Hospital, and K. G. Jebsen Inflammation Research Centre, University of Oslo, Norway; Research Laboratory Nordland Hospital, Bodø, and K. G. Jebsen TREC, University of Tromsø, Tromsø, Norway; Centre of Molecular Inflammation, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address:

Research during past decades made it evident that complement is involved in more tasks than fighting infections, but has important roles in other immune surveillance and housekeeping functions. If the balance between complement activation and regulation is out of tune, however, complement can quickly turn against the host and contribute to adverse processes that result in various clinical conditions. Whereas clinical awareness was initially focused on complement deficiencies, excessive activation and insufficient regulation are frequently the dominant factors in complement-related disorders. Read More

Front Cell Infect Microbiol 2017 16;7:73. Epub 2017 Mar 16.

Biology Centre of the Czech Academy of Sciences, Institute of Parasitology Ceske Budejovice, Czechia.

The present concept of the transmission of Lyme disease from -infected sp. ticks to the naïve host assumes that a low number of spirochetes that manage to penetrate the midgut epithelium migrate through the hemocoel to the salivary glands and subsequently infect the host with the aid of immunomodulatory compounds present in tick saliva. Therefore, humoral and/or cellular immune reactions within the tick hemocoel may play an important role in tick competence to act as a vector for borreliosis. Read More

Clin Exp Nephrol 2018 Feb 24;22(1):3-14. Epub 2017 Mar 24.

Renal Replacement Therapy, Division of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

The complement activation system plays important roles to maintain homeostasis in the host and to fight foreign invaders to protect the host. Therefore, the complement system is considered a core part of innate immunity which also cross-talks to acquired immunity. In the history of nephrology, the complement system is familiar to us, because complement protein or fragment deposition, including C3, C4, C1q, and/or C4d, is routinely estimated by immunohistochemistry to diagnose renal pathologies. Read More

World J Transplant 2016 Dec;6(4):632-645

Maurizio Salvadori, Elisabetta Bertoni, Department of Renal Transplantation, Careggi University Hospital, 50139 Florence, Italy.

The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss after kidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome (HUS), the membranoproliferative glomerulonephritis (MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital (genetic) or acquired (auto-antibodies) modifications of the alternative pathway of complement. Read More

Clin Exp Hypertens 2017 5;39(1):42-49. Epub 2017 Jan 5.

a Nutritional Epidemiology Institute and School of Public Health , Tianjin Medical University , Tianjin , China.

Prehypertension is a public health epidemic associated with various adverse outcomes, but can be reversed by timely intervention. However, little attention has been paid to prehypertension. Complement C3 is a central hub of complement-related immune system. Read More

J Exp Med 2016 10 3;213(11):2365-2382. Epub 2016 Oct 3.

Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305

Cell death and release of proinflammatory mediators contribute to mortality during sepsis. Specifically, caspase-11-dependent cell death contributes to pathology and decreases in survival time in sepsis models. Priming of the host cell, through TLR4 and interferon receptors, induces caspase-11 expression, and cytosolic LPS directly stimulates caspase-11 activation, promoting the release of proinflammatory cytokines through pyroptosis and caspase-1 activation. Read More

Asia Pac J Ophthalmol (Phila) 2016 Jul-Aug;5(4):229-35

From Narayana Nethralaya, Narayana Health City, Bangalore, India.

Age-related macular degeneration (AMD), widely prevalent across the globe, is a major stakeholder among adult visual morbidity and blindness, not only in the Western world but also in Asia. Several risk factors have been identified, including critical genetic factors, which were never imagined 2 decades ago. The etiopathogenesis is emerging to demonstrate that immune and complement-related inflammation pathway members chronically exposed to environmental insults could justifiably influence disease morbidity and treatment outcomes. Read More

Ann Hematol 2016 Sep 9;95(9):1419-27. Epub 2016 Jul 9.

Department of Surgical and Medical Therapeutics, School of Medicine, University of Extremadura, Av. Elvas s/n 06071, Badajoz, Spain.

Hyperhemolysis syndrome (HHS) is characterized by severe intravascular hemolysis with a decrease in the reticulocyte count, which is triggered and aggravated by transfusion and cannot be explained by standard immunohematological studies. A nationwide study was conducted in order to retrospectively identify thalassemia patients with HHS in Spain in order to assess pre-disposing mechanisms for this syndrome. For this, the expression of adhesion (CD49, CD36) and complement-related molecules (C3a, CD59) and the levels of reticulocyte apoptosis and macrophage activation were measured in 4 thalassemia patients with HHS, 14 patients without HHS, and 10 healthy subjects. Read More

PLoS One 2016 6;11(7):e0157413. Epub 2016 Jul 6.

Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Shanghai Ocean University, Ministry of Education, Shanghai 201306, PR China.

The grass carp (Ctenopharyngodon idella) is an important commercial farmed herbivorous fish species in China, but is susceptible to Aeromonas hydrophila infections. In the present study, we performed de novo RNA-Seq sequencing of spleen tissue from specimens of a disease-resistant family, which were given intra-peritoneal injections containing PBS with or without a dose of A. hydrophila. Read More

Fish Shellfish Immunol 2016 Feb 12;49:163-76. Epub 2015 Dec 12.

School of Marine and Atmospheric Sciences, Stony Brook University, Stony Brook, NY, 11794, USA. Electronic address:

Quahog Parasite Unknown (QPX) is a fatal protistan parasite that causes severe losses in the hard clam (Mercenaria mercenaria) fisheries along the northeastern coast of the US. Field and laboratory studies of QPX disease have demonstrated a major role for water temperature and M. mercenaria genetic origin in disease development. Read More

Am J Geriatr Psychiatry 2015 Dec 24;23(12):1290-1296. Epub 2015 Jun 24.

Centre for Public Health, Queen's University of Belfast, UK.

Objectives: Given the clinical and pathological similarities between age-related macular degeneration (AMD) and Alzheimer disease (AD), to assess whether AMD-associated single nucleotide polymorphisms (SNPs), including those from complement-related genes, are associated with AD.

Design: A case-control association study-type design.

Setting: A UK tertiary care dementia clinic. Read More

J Am Soc Nephrol 2016 Jan 2;27(1):27-39. Epub 2015 Sep 2.

Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany; and

The bidirectional causality between kidney injury and inflammation remains an area of unexpected discoveries. The last decade unraveled the molecular mechanisms of sterile inflammation, which established danger signaling via pattern recognition receptors as a new concept of kidney injury-related inflammation. In contrast, renal cell necrosis remained considered a passive process executed either by the complement-related membrane attack complex, exotoxins, or cytotoxic T cells. Read More

Ther Adv Hematol 2015 Aug;6(4):171-85

Department of Paediatric Nephrology, Radboud University Medical Centre, Amalia Children's Hospital, Nijmegen, The Netherlands.

Complement activation plays a major role in several renal pathophysiological conditions. The three pathways of complement lead to C3 activation, followed by the formation of the anaphylatoxin C5a and the terminal membrane attack complex (MAC) in blood and at complement activating surfaces, lead to a cascade of events responsible for inflammation and for the induction of cell lysis. In case of ongoing uncontrolled complement activation, endothelial cells activation takes place, leading to events in which at the end thrombotic microangiopathy can occur. Read More

Acc Chem Res 2015 Aug 21;48(8):2344-53. Epub 2015 Jul 21.

Department of Chemistry, University of California, Irvine, California 92697-2025, United States.

This Account presents the development of a suite of stereospecific alkyl-alkyl cross-coupling reactions employing nickel catalysts. Our reactions complement related nickel-catalyzed stereoconvergent cross-coupling reactions from a stereochemical and mechanistic perspective. Most reactions of alkyl electrophiles with low-valent nickel complexes proceed through alkyl radicals and thus are stereoablative; the correct enantioselective catalyst can favor the formation of one enantiomer. Read More

Clin Exp Nephrol 2016 Apr 9;20(2):265-72. Epub 2015 Jul 9.

Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.

Background: Atypical hemolytic uremic syndrome (aHUS) is a severe life-threatening disease with frequent progression to end-stage renal disease (ESRD). Eculizumab, a humanized anti-C5 monoclonal antibody targeting the activated complement pathway, has recently been introduced as a novel therapy against aHUS. We, therefore, investigated the efficacy and safety of eculizumab in Japanese pediatric patients. Read More

Front Immunol 2015 26;6:257. Epub 2015 May 26.

UMRS 1138, Centre de Recherche des Cordeliers, INSERM , Paris , France ; UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Paris Cité, Université Paris Descartes , Paris , France ; UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, UPMC Université Paris 06 , Paris , France.

The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. Read More

Rinsho Ketsueki 2015 Feb;56(2):185-93

Department of Blood Transfusion Medicine, Nara Medical University.

Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. The term aHUS was historically used to distinguish this disorder from Shiga-toxin producing Escherichia coli (STEC)-HUS. Many aHUS cases (approximately 70%) are reportedly caused by uncontrolled complement activation due to genetic mutations in the alternative pathway, including complement factor H (CFH), complement factor I (CFI), membrane cofactor protein (MCP), thrombomodulin (THBD), complement component C3 (C3), and complement factor B (CFB). Read More

Mol Cell Neurosci 2014 Nov;63:83-95

Several studies have shown that elevated plasma cholesterol levels (i.e. hypercholesterolemia) serve as a risk factor for late-onset Alzheimer's disease (AD). Read More

Pediatr Int 2015 Jun 7;57(3):431-8. Epub 2015 Feb 7.

Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease with a genetic predisposition. Few studies have evaluated the disease in the Asian population. We studied a Korean pediatric cohort to delineate the clinical characteristics and genotypes. Read More

Front Immunol 2014 23;5:459. Epub 2014 Sep 23.

Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark.

Host responses against invading pathogens are basic physiological reactions of all living organisms. Since the appearance of the first eukaryotic cells, a series of defense mechanisms have evolved in order to secure cellular integrity, homeostasis, and survival of the host. Invertebrates, ranging from protozoans to metazoans, possess cellular receptors, which bind to foreign elements and differentiate self from non-self. Read More

ChemMedChem 2014 Oct 23;9(10):2223-6. Epub 2014 Jul 23.

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 401 Stellar-Chance Laboratories, Philadelphia, PA 19104 (USA).

The compstatin family of complement inhibitors has shown promise in various immuno-inflammatory disorders. Although recent analogues show beneficial pharmacokinetics, further extension of the plasma half-life is expected to benefit systemic application of these peptidic inhibitors. We therefore synthesized conjugates of compstatin analogues and albumin-binding molecules (ABM) to increase circulatory residence. Read More

Dis Aquat Organ 2014 Jul;109(3):187-99

Institute of Science and Technology in Medicine, School of Life Sciences, Keele University, ST5 5BG Keele, UK.

Cyprinid herpesvirus 3 (CyHV-3) is the aetiological agent of a highly virulent and lethal disease of common carp Cyprinus carpio and its ornamental koi varieties. However, specific knowledge about immune mechanisms behind the infection process is very limited. We aimed to evaluate the effect of the CyHV-3 infection on the profile of 2 major components of the common carp immune acute phase response: the C-reactive protein (CRP) and the complement system. Read More

Fish Shellfish Immunol 2014 Nov 2;41(1):2-11. Epub 2014 Jun 2.

Institut Universitaire Européen de la Mer, Plouzané, France.

Brown Ring Disease (BRD) is a bacterial infection affecting the economically-important clam Ruditapes philippinarum. The disease is caused by a bacterium, Vibrio tapetis, that colonizes the edge of the mantle, altering the biomineralization process and normal shell growth. Altered organic shell matrices accumulate on the inner face of the shell leading to the formation of the typical brown ring in the extrapallial space (between the mantle and the shell). Read More

J Neuroinflammation 2014 Mar 28;11:61. Epub 2014 Mar 28.

Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.

Background: Gangliosides, sialic acid-containing glycosphingolipids, are highly expressed in nervous systems of vertebrates and have been considered to be involved in the development, differentiation, and function of nervous tissues. Recent studies with gene-engineered animals have revealed that they play roles in the maintenance and repair of nervous tissues. In particular, knockout (KO) mice of various ganglioside synthase genes have exhibited progressive neurodegeneration with aging. Read More

Oncol Rep 2014 Feb 28;31(2):557-64. Epub 2013 Nov 28.

Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing 100071, P.R. China.

The therapeutic potential of membrane complement regulatory protein (mCRP)-neutralizing antibodies is unsatisfactory, which perhaps lies in the complex role of mCRPs in tumor occurrence and development. As a member of the mCRPs, CD46 is a transmembrane protein with a cytoplasmic domain and is implicated more in the control of the alternative complement pathway than of the classical complement pathway. Growing evidence has revealed that both the CD46 signaling pathway and microRNAs (miRNAs) play an important role in the development and progression of hepatocellular carcinoma (HCC). Read More

Arch Immunol Ther Exp (Warsz) 2014 Feb 13;62(1):47-57. Epub 2013 Sep 13.

Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wrocław, Poland,

Serum complement cascade, a part of innate immunity required for host protection against invading pathogens, is also a mediator of various forms of disease and injury. It is activated by classical, lectin, and alternative pathways that lead to activation of C3 component by C3 convertases, release of C3b opsonin, C5 conversion and eventually membrane attack complex formation. The tightly regulated activation process yields also C3a and C5a anaphylatoxins, which target a broad spectrum of immune and non-immune cells. Read More

J Immunol 2013 Oct 6;191(7):3858-66. Epub 2013 Sep 6.

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104;

Activation of the complement system is primarily initiated by pathogen- and damage-associated molecular patterns on cellular surfaces. However, there is increasing evidence for direct activation of individual complement components by extrinsic proteinases as part of an intricate crosstalk between physiological effector systems. We hypothesized that kallikrein-related peptidases (KLKs), previously known to regulate inflammation via proteinase-activated receptors, can also play a substantial role in innate immune responses via complement. Read More

PLoS One 2013 26;8(4):e62257. Epub 2013 Apr 26.

Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany.

Inflammatory bowel diseases are a critical public health issue, and as treatment options remain limited, there is a need to unravel the underlying pathomechanisms in order to identify new therapeutic targets. Complement activation was found in patients suffering from inflammatory bowel disease, and the complement anaphylatoxin C5a and its receptor C5aR have been implicated in disease pathogenesis in animal models of bowel inflammation. To further characterize complement-related pathomechanisms in inflammatory bowel disease, we have investigated the role of the anaphylatoxin C3a receptor in acute dextran sulfate sodium-induced colitis in mice. Read More

Adv Exp Med Biol 2013 ;735:301-13

Department of Pathology and Laboratory Medicine, University of Pennsylvania, 401A Stellar-Chance Building, 422 Curie Blvd, Philadelphia, PA 19104, USA.

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. Read More

Adv Exp Med Biol 2013 ;735:247-55

Division of Transplantation Immunology and Mucosal Biology, MRC Centre for Transplantation, 5th Floor, Tower Wing, Great Maze Pond, Guy's Hospital, London SE1 9RT, UK.

Complement activation occurs in at least two phases when an organ is transplanted into a naive recipient: during reperfusion with recipient blood particularly when the donor organ has undergone a significant period of ischaemia and then during acute rejection once the recipient immune system has recognised the donor tissue as non-self. Both of these reactions are most obvious in the extravascular compartment of the transplanted organ and involve local synthesis of some of the key complement components as well as loss of controls that limit the activation of the pivotal component C3. In contrast, sensitised individuals with pre-existing circulating antibodies have an immediate reaction against the transplant organ that is also complement dependent but is enacted in the intravascular space. Read More