Seppo Meri

Seppo Meri
University of Helsinki | HY · Haartman Institute

About

525
Publications
42,357
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19,339
Citations
Additional affiliations
January 2012 - present
University of Helsinki
Position
  • Professor of Immunology

Publications

Publications (525)
Article
Full-text available
Background Vaginal microbiome and the local innate immune defense, including the complement system, contribute to anti- and proinflammatory homeostasis during pregnancy and parturition. The relationship between commensal vaginal bacteria and complement activation during pregnancy and delivery is not known. Objective To study the association of the...
Article
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Cutaneous squamous cell carcinoma (cSCC) is the most prevalent metastatic skin cancer. Previous studies have demonstrated the autocrine role of complement components in cSCC progression. We have investigated factor D (FD), the key enzyme of the alternative complement pathway, in the development of cSCC. RT-qPCR analysis of cSCC cell lines and norma...
Article
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Small animal models are of crucial importance for assessing COVID-19 countermeasures. Common laboratory mice would be well-suited for this purpose but are not susceptible to infection with wild-type SARS-CoV-2. However, the development of mouse-adapted virus strains has revealed key mutations in the SARS-CoV-2 spike protein that increase infectivit...
Article
Background Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare coagulation disorder reported after administration of COVID-19 adenovirus-vectored vaccines. VITT is mediated by anti-platelet factor 4 (PF4) antibodies activating platelets through the Fcγ-receptor II (FcγRII), and it is associated with strong fibrin turnover. The complement s...
Article
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Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer with increasing incidence worldwide. Previous studies have demonstrated the role of complement system in cSCC progression. In this study we have investigated the mechanistic role of serine protease C1r, a component of the classical pathway of complement system, in cS...
Article
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Inhibition of membrane‐bound pyrophosphatase (mPPase) with small molecules offer a new approach in the fight against pathogenic protozoan parasites. mPPases are absent in humans, but they are essential for many protists as they couple pyrophosphate hydrolysis to the active transport of protons or sodium ions across acidocalcisomal membranes. So far...
Preprint
Small animal models are of crucial importance for assessing COVID-19 countermeasures. Common laboratory mice would be well-suited for this purpose but are not susceptible to infection with wild-type SARS-CoV-2. Herein we show that the SARS-CoV-2 beta variant attains infectibility to BALB/c mice and causes pulmonary changes consistent with COVID-19.
Article
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Objective: To study genetic variants and their function within genes coding for complement receptors in preeclampsia. Design: A case-control study. Setting: Preeclampsia is a common vascular disease of pregnancy. The clearance of placenta-derived material is one of the functions of the complement system in pregnancy. Population: We genotyped 500...
Article
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High density lipoproteins (HDL) are a group of different subpopulations of sialylated particles that have an essential role in the reverse cholesterol transport (RCT) pathway. Importantly, changes in the protein and lipid composition of HDL may lead to the formation of particles with reduced atheroprotective properties. Here, we show that Streptoco...
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Narcolepsy type 1 (NT1) is a chronic neurological disorder having a strong association with HLA-DQB1*0602, thereby suggesting an immunological origin. Increased risk of NT1 has been reported among children or adolescents vaccinated with AS03 adjuvant-supplemented pandemic H1N1 influenza A vaccine, Pandemrix. Here we show that pediatric Pandemrix-as...
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The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing globally. Here, we have studied the functional role of complement factor I (CFI) in the progression of cSCC. CFI was knocked down in cSCC cells and RNA‐seq analysis was performed. Significant down‐regulation of genes in IPA biofunction categories Proliferation of cells and Grow...
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Complement-mediated inflammation or dysregulation in lipid metabolism are associated with the pathogenesis of several diseases. These include age-related macular degeneration (AMD), C3 glomerulonephritis (C3GN), dense deposit disease (DDD), atherosclerosis, and Alzheimer’s disease (AD). In all these diseases, formation of characteristic lipid-rich...
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BACKGROUND: Human pregnancy alters profoundly the immune system. The local involvement and mechanisms of activation of the complement system in the cervicovaginal milieu during pregnancy and delivery remain unexplored. OBJECTIVES: To determine whether normal pregnancy and delivery are associated with local activation of complement or changes in the...
Article
Streptococci are a broad group of Gram‐positive bacteria. This genus includes various human pathogens causing significant morbidity and mortality. Two of the most important human pathogens are Streptococcus pneumoniae (pneumococcus) and Streptococcus pyogenes (group A streptococcus or GAS). Streptococcal pathogens have evolved to express virulence...
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We have analyzed T cell receptor repertoires in a unique set of thymus samples from a pair of monozygotic twins. While genetics affect the V(D)J rearrangement and generation of junctional sequences, the thymic selections seem largely stochastic and import no detectable inheritable effect at clonal level.
Article
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Narcolepsy type 1, likely an immune-mediated disease, is characterized by excessive daytime sleepiness and cataplexy. The disease is strongly associated with human leukocyte antigen (HLA) DQB1*06:02. A significant increase in the incidence of childhood and adolescent narcolepsy was observed after a vaccination campaign with AS03-adjuvanted Pandemri...
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The malaria parasite has for long been thought to escape host complement attack as a survival strategy. However, it was only recently that complement evasion mechanisms of the parasite were described. Simultaneously, the role of complement in antibody‐mediated naturally acquired and vaccine‐induced protection against malaria has also been reported....
Article
Gangliosides are structurally and functionally polymorphic sialic acid containing glycosphingolipids that are widely distributed in the human body. They play important roles in protecting us against immune attacks, yet they can become targets for autoimmunity and act as receptors for microbes, like the influenza viruses, and toxins, such as the cho...
Article
The incidence of skin cancers is increasing worldwide. The epidermis is the surface layer of the skin and the main cell type is the keratinocyte. Keratinocyte‐derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic (meaning it can spread) skin cancer and it is responsible for 20% of skin cancer related deaths. The main risk f...
Article
皮肤癌的发病率在全世界范围内正在增加。表皮是皮肤的表层,主要细胞类型是角质形成细胞。角质形成细胞源性皮肤鳞状细胞癌 (cSCC) 是最常见的转移性(意味着它可以扩散)皮肤癌,其占皮肤癌相关死亡的 20%。cSCC 的主要风险因素包括长期暴露于太阳紫外线辐射。 cSCC 的进展如下所示:它以称为光化性角化病 (AK) 的癌前形式(尚未癌变)开始,然后变成局限性 cSCC,然后是原位 cSCC (cSCCIS),最终成为浸润性和转移性 cSCC。 这项来自芬兰的研究旨在寻找能够预测 cSCC 进展和侵袭性的生物标志物(体内的化学物质,作为疾病的体征)。 作者发现,与正常表皮角质形成细胞和正常皮肤相比,cSCC 细胞和肿瘤中称为 C1r 和 C1s(在我们的免疫系统中起作用)的酶的 mRNA(信使...
Article
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Membrane-bound pyrophosphatases (mPPases) regulate energy homeostasis in pathogenic protozoan parasites and lack human homologues, which makes them promising targets in e.g. malaria. Yet only few nonphosphorus inhibitors have been reported so far. Here, we explore an isoxazole fragment hit, leading to the discovery of small mPPase inhibitors with 6...
Article
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Preeclampsia is a serious vascular complication of the human pregnancy, whose etiology is still poorly understood. In preeclampsia, exacerbated apoptosis and fragmentation of the placental tissue occurs due to developmental qualities of the placental trophoblast cells and/or mechanical and oxidative distress to the syncytiotrophoblast, which lines...
Article
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It is essential for early human life that mucosal immunological responses to developing embryos are tightly regulated. An imbalance of the complement system is a common feature of pregnancy complications. We hereby present the first full analysis of the expression and deposition of complement molecules in human pre-implantation embryos. Thus, far,...
Article
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The functions of pentraxins, like C-reactive protein (CRP), serum amyloid protein P (SAP) and pentraxin-3 (PTX3), are to coordinate spatially and temporally targeted clearance of injured tissue components, to protect against infections and to regulate related inflammation together with the complement system. For this, pentraxins have a dual relatio...
Article
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The most frequent form of hemolytic-uremic syndrome (HUS) is associated with infections caused by Shiga-like toxin-producing Enterohaemorrhagic Escherichia coli (STEC). In rarer cases HUS can be triggered by Streptococcus pneumoniae. While production of Shiga-like toxins explains STEC-HUS, the mechanisms of pneumococcal HUS are less well-known. S....
Article
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Background Incidence of epidermal keratinocyte‐derived cutaneous squamous cell carcinoma (cSCC) is increasing worldwide. Objectives To study the role of complement classical pathway components C1q, C1r and C1s in the progression of cSCC. Methods The mRNA levels of C1Q subunits, C1R and C1S in cSCC cell lines, normal human epidermal keratinocytes...
Article
Full-text available
Membrane-bound pyrophosphatases are homodimeric integral membrane proteins that hydrolyze pyrophosphate into orthophosphates, coupled to the active transport of protons or sodium ions across membranes. They are important in the life cycle of bacteria, archaea, plants, and parasitic protists, but no homologous proteins exist in vertebrates, making t...
Preprint
Full-text available
It is essential for early human life that immunological responses to developing embryos are tightly regulated. An imbalance in the activation and regulation of the human complement system occurs in pregnancy complications, such as pre-eclampsia and recurrent miscarriage. We hereby present the first full analysis of the expression and deposition of...
Preprint
Full-text available
Membrane-bound pyrophosphatases are homodimeric integral membrane proteins that hydrolyse pyrophosphate into orthophosphates, coupled to the active transport of protons or sodium ions across membranes. They are important in the life cycle of bacteria, archaea, plants, and protist parasites, but no homologous proteins exist in vertebrates, making th...
Article
Full-text available
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired syndrome characterized by intravascular hemolysis, thrombosis, and bone marrow failure. The disease is caused by a mutation in the PIG-A gene that leads to the lack of glycosylphosphatidylinositol-anchored complement regulatory molecules CD55 and CD59 on affected blood cell surfaces. In previ...
Article
The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing worldwide. We have analyzed the role of complement components C1r and C1s in the progression of cSCC. Analysis of cSCC cell lines (n=8) and normal human epidermal keratinocytes (NHEK)(n=11) with oligonucleotide arrays, RNA-seq and quantitative RT-PCR revealed significantly elev...
Article
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Factor H is an important regulator of complement activation in plasma and on cell surfaces in both humans and mice. If FH function is compromised, inappropriate complement activation on self‐surfaces can have disastrous effects as seen in the kidney diseases atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy. Since FH constructs have b...
Article
It has become increasingly apparent that the complement system, being an ancient defense mechanism, is not operative only in the extracellular milieu but also intracellularly. In addition to the known synthetic machinery in the liver and by macrophages, many other cell types, including lymphocytes, adipocytes and epithelial cells produce selected c...
Article
Background: Matrix metalloproteinase 8 (MMP-8) is a proinflammatory enzyme expressed mainly by neutrophils. Elevated serum and plasma concentrations of MMP-8 are associated with the risk for and outcome of cardiovascular diseases (CVDs). The origin of circulating MMP-8 is not completely clear. Methods and results: We performed a genome-wide asso...
Article
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The case-fatality rate of hantavirus disease depends strongly on the causative hantavirus, ranging from 0.1% to 40%. However, the pathogenesis is not fully understood and at present no licensed therapies exist. We describe fatal cases caused by Puumala hantavirus indicating involvement of complement activation and vascular leakage.
Article
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Background: Immune system involvement is suggested as an underlying cause for Doberman hepatitis (DH) based on female predisposition, lymphocyte infiltration, abnormal hepatocyte expression of major histocompatibility complex class II antigens, and homozygosity for dog leukocyte antigen DRB1*00601. Objective: To measure serum antinuclear antibod...
Article
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Background Mosquitoes are vectors for many diseases such as malaria. Insecticide-treated bed nets and indoor residual spraying of insecticides are the principal malaria vector control tools used to prevent malaria in the tropics. Other interventions aim at reducing man-vector contact. For example, house screening provides additive or synergistic ef...
Article
Complement C4 genes are linked to pediatric inflammatory bowel disease (PIBD), but the mechanisms have remained unclear. We examined the influence of C4B gene number on intestinal microbiota and in vitro serum complement activation by intestinal microbes in PIBD patients. Complement C4A and C4B gene numbers were determined by genomic RT-PCR from 64...
Article
Preeclampsia is a common pregnancy-specific vascular disorder characterized by new-onset hypertension and proteinuria during the second half of pregnancy. Predisposition to preeclampsia is in part heritable. It is associated with an increased risk of cardiovascular disease later in life. We have sequenced 124 candidate genes implicated in preeclamp...
Article
An autoimmune background is suspected for Doberman hepatitis (DH). It is based on the finding of mononuclear cell infiltrates in the liver, strong female bias, association to the homozygous risk factor dog leukocyte antigen (DLA) allele DRB1*00601 and aberrant major histocompatibility complex (MHC) class II expression on hepatocytes that correlates...
Article
It is becoming increasingly clear that the connections between our immune system and the microbiota colonizing us have a tremendous impact on human health. A number of innate molecular defence mechanisms cooperate to selectively target unwanted microorganisms at the mucosal surfaces. Amongst others these include the complement system, IgA and the S...