Search Our Scientific Publications & Authors

Kidney Int Rep 2022 Jun 4;7(6):1219-1228. Epub 2022 Apr 4.

Renal Division, Peking University First Hospital, Beijing, China.

Introduction: Arteriolar microangiopathic (MA) lesions are independent risk factors for IgA nephropathy (IgAN) patient prognosis, and the underlying mechanism remains to be elucidated. The complement plays an important role in IgAN and thrombotic microangiopathy; however, its role in MA lesions in IgAN remains unclear.

Methods: Immunohistochemistry was performed to detect arteriolar complement deposition. Read More

Front Med (Lausanne) 2022 11;9:845679. Epub 2022 Apr 11.

Department of Nephrology, China-Japan Friendship Hospital, Beijing, China.

Introduction: Key genes involved in tubulointerstitial injury may influence the development and progression of diabetic nephropathy (DN). We investigated whether complement-related genes are linked to the mechanism underlying tubulointerstitial injury in DN.

Methods: We analyzed the microarray data of 17 tubulointerstitial tissue samples from DN patients and 21 normal controls from the Gene Expression Omnibus. Read More

Brain Behav Immun 2022 05 1;102:237-250. Epub 2022 Mar 1.

Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Recent studies have reported that complement-related proteins modulate brain development through regulating synapse processes in the cortex. CSMD3 belongs to a group of putative complement control proteins. However, its role in the central nervous system and synaptogenesis remains largely unknown. Read More

J Cell Mol Med 2022 03 22;26(5):1445-1455. Epub 2022 Jan 22.

Faculty of Engineering & Information Technology, University of Technology Sydney, Ultimo, NSW, Australia.

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Read More

J Diabetes Investig 2022 May 10;13(5):839-849. Epub 2022 Jan 10.

Department of Nephrology, China-Japan Friendship Hospital, Beijing, China.

Aims/introduction: It is not unclear whether the complement system is involved in the pathogenesis of diabetic nephropathy (DN). We explored the role of the complement system in glomeruli from patients with DN using integrated transcriptomic bioinformatics analysis and renal histopathology.

Materials And Methods: Four datasets (GSE30528, GSE104948, GSE96804 and GSE99339) from the Gene Expression Omnibus database were integrated. Read More

J Mol Med (Berl) 2022 02 29;100(2):269-284. Epub 2021 Oct 29.

Nephrology Research Group, L'Hôtel-Dieu de Québec Research Center, Department of Medicine, Faculty of Medicine, Laval University, Quebec, QC, G1R2J6, Canada.

Atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) have been linked to mutations in many of the proteins that are involved in alternative complement pathway activation. Age and etiology confounded, the prevalence of such mutations has been reported to be over 30 to 50% in these diseases. However, the cohorts studied included many children or individuals with a familial history of complement-related disorders and genetic tests were usually limited to exome sequencing of known causative or risk-associated genes. Read More

Blood 2022 Jun;139(25):3571-3582

Severe Aplastic Anemia Working Party, European Group for Bone Marrow Transplantation.

Complement is an elaborate system of innate immunity. Genetic variants and autoantibodies leading to excessive complement activation are implicated in a variety of human diseases. Among them, the hematologic disease paroxysmal nocturnal hemoglobinuria (PNH) remains the prototypic model of complement activation and inhibition. Read More

Cells 2021 07 17;10(7). Epub 2021 Jul 17.

Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, 40530 Gothenburg, Sweden.

The complement system, an effector arm of the innate immune system that plays a critical role in tissue inflammation, the elimination of pathogens and the clearance of dead cells and cell debris, has emerged as a regulator of many processes in the central nervous system, including neural cell genesis and migration, control of synapse number and function, and modulation of glial cell responses. Complement dysfunction has also been put forward as a major contributor to neurological disease. Astrocytes are neuroectoderm-derived glial cells that maintain water and ionic homeostasis, and control cerebral blood flow and multiple aspects of neuronal functioning. Read More

J Fish Dis 2021 Nov 5;44(11):1697-1709. Epub 2021 Jul 5.

Aquaculture Research Group, Moredun Research Institute, Pentlands Science Park, Penicuik (Edinburgh), UK.

Cardiomyopathy syndrome (CMS), caused by piscine myocarditis virus (PMCV), is a serious challenge to Atlantic salmon (Salmo salar L.) aquaculture. Regrettably, husbandry techniques are the only tool to manage CMS outbreaks, and no prophylactic measures are available at present. Read More

Lupus 2021 Sep 1;30(10):1671-1678. Epub 2021 Jul 1.

Division of Rheumatology, New York University Grossman School of Medicine, New York, USA.

Introduction: Activation of the complement pathway by immune complexes is a key feature of systemic lupus erythematosus (SLE) and SLE glomerulonephritis, which translates into low levels of C3 and C4 during active disease. C3 glomerulonephritis (C3GN) is part of a broader group of rare renal diseases, the C3 glomerulopathies, characterized by prominent C3 accumulation in the glomeruli with minimal to no immunoglobulin (Ig) deposition secondary to dysregulation of the alternative pathway of the complement system. Distinguishing lupus nephritis from other complement-mediated kidney disorders, including C3GN, represents a diagnostic challenge with potential therapeutic implications. Read More

Hemodial Int 2021 10 16;25(4):479-488. Epub 2021 Jun 16.

Laboratory of Molecular Medicine, Department of Clinical Immunology, University of Copenhagen, Copenhagen, Denmark.

Introduction: This study aimed to investigate changes in complement system-related molecules in patients undergoing hemodialysis.

Methods: Patients >18 years of age on maintenance hemodialysis were included. Using enzyme-linked immunosorbent assays (ELISA) methods complement related molecules ficolin-1, ficolin-2, ficolin-3 mannose-binding lectin, long pentraxin 3, complement activation products C3c, and complement activation potentials were measured before and after a single hemodialysis treatment. Read More

J Am Soc Nephrol 2021 08 3;32(8):2031-2047. Epub 2021 May 3.

Division of Nephrology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York

Background: Genetic variants in complement genes have been associated with a wide range of human disease states, but well-powered genetic association studies of complement activation have not been performed in large multiethnic cohorts.

Methods: We performed medical records-based genome-wide and phenome-wide association studies for plasma C3 and C4 levels among participants of the Electronic Medical Records and Genomics (eMERGE) network.

Results: In a GWAS for C3 levels in 3949 individuals, we detected two genome-wide significant loci: chr. Read More

Biomedicines 2021 Apr 7;9(4). Epub 2021 Apr 7.

Dompé Farmaceutici SpA, 67100 L'Aquila, Italy.

The complement system is a key component of innate immunity since it plays a critical role in inflammation and defense against common pathogens. However, an inappropriate activation of the complement system is involved in numerous disorders, including peripheral neuropathies. Current strategies for neuropathy-related pain fail to achieve adequate pain relief, and although several therapies are used to alleviate symptoms, approved disease-modifying treatments are unavailable. Read More

Methods Mol Biol 2021 ;2227:1-20

INSERM, UMRS 1138, Inflammation, Complement and Cancer Team, Centre de Recherche des Cordelier, Sorbonne Universités, Université de Paris, Paris, France.

The complement cascade is an evolutionary ancient innate immune defense system, playing a major role in the defense against infections. Its function in maintaining host homeostasis on activated cells has been emphasized by the crucial role of its overactivation in ever growing number of diseases, such as atypical hemolytic uremic syndrome (aHUS), autoimmune diseases as systemic lupus erythematosus (SLE), C3 glomerulopathies (C3GN), age-related macular degeneration (AMD), graft rejection, Alzheimer disease, and cancer, to name just a few. The last decade of research on complement has extended its implication in many pathological processes, offering new insights to potential therapeutic targets and asserting the necessity of reliable, sensitive, specific, accurate, and reproducible biomarkers to decipher complement role in pathology. Read More

Clin Immunol 2021 05 13;226:108726. Epub 2021 Apr 13.

Hematology Division, Department of Internal Medicine, Johns Hopkins University, Baltimore, USA.

Recent studies suggest excessive complement activation in severe coronavirus disease-19 (COVID-19). The latter shares common characteristics with complement-mediated thrombotic microangiopathy (TMA). We hypothesized that genetic susceptibility would be evident in patients with severe COVID-19 (similar to TMA) and associated with disease severity. Read More

Mol Cell Proteomics 2021 3;20:100068. Epub 2021 Mar 3.

CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China; College of Life Sciences, University of the Chinese Academy of Sciences, Beijing, China; Clinical Laboratory of BGI Health, BGI-Shenzhen, Shenzhen, China. Electronic address:

Signet ring cell carcinoma (SRCC) is a histological subtype of gastric cancer with distinct features in multiple aspects compared with adenocarcinomas (ACs). The lack of a systematic molecular overview of this disease has led to slow progress in its clinical practice. In the present proteomics study, gastric tissues were collected from tumors and adjacent tissues, including 14 SRCCs and 34 ACs, and laser capture microdissection (LCM) was employed to eradicate the cellular heterogeneity of the tissues. Read More

PLoS One 2021 12;16(2):e0240707. Epub 2021 Feb 12.

Division of Allergy and Immunology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States of America.

Rheumatoid arthritis (RA)-associated lung disease is a leading cause of mortality in RA, yet the mechanisms linking lung disease and RA remain unknown. Using an established murine model of RA-associated lung disease combining collagen-induced arthritis (CIA) with organic dust extract (ODE)-induced airway inflammation, differences among lung immune cell populations were analyzed by single cell RNA-sequencing. Additionally, four lung myeloid-derived immune cell populations including macrophages, monocytes/macrophages, monocytes, and neutrophils were isolated by fluorescence cell sorting and gene expression was determined by NanoString analysis. Read More

Vaccines (Basel) 2021 Jan 20;9(2). Epub 2021 Jan 20.

Laboratory of Molecular Microbiology and Biotechnology (LAMMB), Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.

Ebolavirus Disease (EVD) is a severe haemorrhagic fever that occurs in epidemic outbreaks, with a high fatality rate and no specific therapies available. rVSVΔG-ZEBOV-GP (Ervebo), a live-attenuated recombinant vesicular stomatitis virus vector expressing the glycoprotein G of Zaire Ebolavirus, is the first vaccine approved for prevention of EVD. Both innate and adaptive responses are deemed to be involved in vaccine-induced protection, yet the mechanisms are not fully elucidated. Read More

Front Cell Neurosci 2020 7;14:600656. Epub 2021 Jan 7.

Department of Immunology, University of Toronto, Toronto, ON, Canada.

The last 15 years have seen an explosion of new findings on the role of complement, a major arm of the immune system, in the central nervous system (CNS) compartment including contributions to cell migration, elimination of synapse during development, aberrant synapse pruning in neurologic disorders, damage to nerve cells in autoimmune diseases, and traumatic injury. Activation of the complement system in multiple sclerosis (MS) is typically thought to occur as part of a primary (auto)immune response from the periphery (the outside) against CNS antigens (the inside). However, evidence of local complement production from CNS-resident cells, intracellular complement functions, and the more recently discovered role of early complement components in shaping synaptic circuits in the absence of inflammation opens up the possibility that complement-related sequelae may start and finish within the brain itself. Read More

Front Microbiol 2020 23;11:608380. Epub 2020 Dec 23.

Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Helminth-derived molecules have the ability to modulate the host immune system. Our previous study identified a tetradecapeptide derived from paramyosin (-pmy) that could bind to human complement component C9 to inhibit its polymerization, making the peptide a candidate therapeutic agent for complement-related immune disorders. Here, the peptide underwent an N-terminal modification with a membrane-targeting signal (a unique myristoylated peptide) to improve its therapeutic efficacy. Read More

Front Immunol 2020 19;11:572326. Epub 2020 Nov 19.

Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Helminths develop strategies to escape host immune responses that facilitate their survival in the hostile host immune environment. , a tissue-dwelling nematode, has developed a sophisticated strategy to escape complement attack. Our previous study demonstrated that secretes calreticulin (CRT) to inhibit host classical complement activation through binding to C1q; however, the C1q binding site in CRT and the specific mechanism involved with complement-related immune evasion remains unknown. Read More

Front Immunol 2020 2;11:1911. Epub 2020 Sep 2.

Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Jena, Germany.

The complement system is part of the innate immune system and plays an important role in the host defense against infectious pathogens. One of the main effects is the opsonization of foreign invaders and subsequent uptake by phagocytosis. Due to the continuous default basal level of active complement molecules, a tight regulation is required to protect the body's own cells (self cells) from opsonization and from complement damage. Read More

J Immunol Methods 2020 11 15;486:112866. Epub 2020 Sep 15.

Department of Biomedicine, Aarhus University, Aarhus, Denmark.

In human autoimmune diseases, low plasma levels of complement factors C3 and C4 are commonly used as a proxy for complement activation. The measurements of C3 and C4 concentrations (the result of synthesis and consumption) however, show low sensitivity in patient follow-up. We find that the estimation of the C3dg fragment released during complement activation is a better parameter for complement activation. Read More

Am J Med Genet B Neuropsychiatr Genet 2020 12 12;183(8):445-453. Epub 2020 Sep 12.

Cognitive Genetics & Cognitive Therapy Group, The Centre for Neuroimaging, Cognition and Genomics (NICOG), School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.

Multiple genome-wide association studies of schizophrenia have reported associations between genetic variants within the MHC region and disease risk, an association that has been partially accounted for by alleles of the complement component 4 (C4) gene. Following on previous findings of association between both C4 and other complement-related variants and memory function, we tested the hypothesis that polygenic scores calculated based on identified schizophrenia risk alleles within the "complement" system would be broadly associated with memory function and associated brain structure. We tested this using a polygenic risk score (PRS) calculated for complement genes, but excluding C4 variants. Read More

J Immunol 2020 10 26;205(7):1778-1786. Epub 2020 Aug 26.

Department of Immunopathology, Sanquin Research, Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, the Netherlands;

The complement system plays an important role in our innate immune system. Complement activation results in clearance of pathogens, immune complex, and apoptotic cells. The host is protected from complement-mediated damage by several complement regulators. Read More

Exp Clin Transplant 2020 01;18(Suppl 1):82-83

From the Department of Pediatric Nephrology, Baskent University, Ankara, Turkey.

Complement dysregulation is related to different glomerular pathologies. Patients with complement dysregulation have high recurrence risk after transplant; however, with trough-effective therapeutics, renal transplant can be an option for these patients. Here, we present 2 boys with renal disease related to complement dysregulation and their outcomes after renal transplant. Read More

J Infect 2020 04 23;80(4):378-387. Epub 2020 Jan 23.

Laboratory of Molecular Medicine, Department of Clinical Immunology, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Objectives: To evaluate the complement related pattern recognition molecules (PRMs) PTX3, MBL, CL-11, ficolin-2 and -3, along with the established marker CRP, to predict 28-day mortality and disease severity of sepsis in patients admitted to the intensive care unit (ICU).

Methods: In a single-center, prospective, observational study 547 patients were included over a period of 18 months. Blood samples were obtained at admission to the ICU and the following 4 days. Read More

Compr Physiol 2019 09 19;9(4):1411-1429. Epub 2019 Sep 19.

College of Medicine, Oman Medical College, Muscat, Oman.

Adipose tissue releases many cytokines and inflammatory factors described as adipokines. In obesity, adipokines released from expanding adipose tissue are implicated in disease progression and metabolic dysfunction. However, mechanisms controlling the progression of adiposity and metabolic complications are not fully understood. Read More

Chem Biodivers 2019 Dec 4;16(12):e1900401. Epub 2019 Dec 4.

Departamento de Patologia Médica, Universidade Federal do Paraná, Setor de Ciências da Saúde, Universidade Federal do Paraná, Rua General Carneiro No. 181, Hospital de Clínicas, CEP: 80060-900, Curitiba, Paraná, Brazil.

The complement system participates in host defense by eliminating microorganisms and triggering inflammation. However, insufficient control or exacerbated complement activation contributes to inflammatory diseases. Since promising antioxidant and anti-inflammatory activities have been identified in Arctium lappa L. Read More

Front Immunol 2019 1;10:2306. Epub 2019 Oct 1.

NYU Langone Transplant Institute, New York, NY, United States.

The complement system is integral to innate immunity, and it is an essential deterrent against infections. The complement apparatus comprises of >30 fluid-phase and surface-bound elements that also engage with the adaptive immune system, clear harmful immune complexes, and orchestrates several salutary physiological processes. An imbalance in the complement system's tightly regulated machinery and the consequent unrestrained complement activation underpins the pathogenesis of a wide array of inflammatory, autoimmune, neoplastic and degenerative disorders. Read More