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756 results on '"Complement C3b Inactivator Proteins"'

1. Beyond factor H: The impact of genetic-risk variants for age-related macular degeneration on circulating factor-H-like 1 and factor-H-related protein concentrations

Author

Cipriani, Valentina, Tierney, Anna, Griffiths, John R, Zuber, Verena, Sergouniotis, Panagiotis I, Yates, John RW, Moore, Anthony T, Bishop, Paul N, Clark, Simon J, and Unwin, Richard D

Subjects
Aging, Macular Degeneration, Neurodegenerative, Eye Disease and Disorders of Vision, Genetics, 2.1 Biological and endogenous factors, Aetiology, Aged, Case-Control Studies, Complement C3b Inactivator Proteins, Complement Factor H, Female, Genetic Predisposition to Disease, Humans, Male, Polymorphism, Single Nucleotide, Risk Factors, Mendelian randomization, age-related macular degeneration, complement factor H, factor H-related, mass spectrometry, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Age-related macular degeneration (AMD) is a leading cause of vision loss; there is strong genetic susceptibility at the complement factor H (CFH) locus. This locus encodes a series of complement regulators: factor H (FH), a splice variant factor-H-like 1 (FHL-1), and five factor-H-related proteins (FHR-1 to FHR-5), all involved in the regulation of complement factor C3b turnover. Little is known about how AMD-associated variants at this locus might influence FHL-1 and FHR protein concentrations. We have used a bespoke targeted mass-spectrometry assay to measure the circulating concentrations of all seven complement regulators and demonstrated elevated concentrations in 352 advanced AMD-affected individuals for all FHR proteins (FHR-1, p = 2.4 × 10-10; FHR-2, p = 6.0 × 10-10; FHR-3, p = 1.5 × 10-5; FHR-4, p = 1.3 × 10-3; FHR-5, p = 1.9 × 10-4) and FHL-1 (p = 4.9 × 10-4) when these individuals were compared to 252 controls, whereas no difference was seen for FH (p = 0.94). Genome-wide association analyses in controls revealed genome-wide-significant signals at the CFH locus for all five FHR proteins, and univariate Mendelian-randomization analyses strongly supported the association of FHR-1, FHR-2, FHR-4, and FHR-5 with AMD susceptibility. These findings provide a strong biochemical explanation for how genetically driven alterations in circulating FHR proteins could be major drivers of AMD and highlight the need for research into FHR protein modulation as a viable therapeutic avenue for AMD.

Published
2021

2. Ocular biomarker profiling after complement factor I gene therapy in geographic atrophy secondary to age-related macular degeneration (Updated November 4, 2024).

Abstract

The article discusses a study on ocular biomarker profiling after complement factor I gene therapy in geographic atrophy secondary to age-related macular degeneration. The study evaluated biomarker data from 28 subjects in a clinical trial to understand target pharmacokinetics/pharmacodynamics and investigate the therapeutic dose. Results showed an increase in FI protein post-treatment, but limited impact on complement activation, suggesting the therapy may not have provided sufficient FI protein to slow GA growth. The study highlights the importance of reviewing vitreous humor biomarkers for future clinical development. [Extracted from the article]

Published
2024

3. Patent Issued for Complement factor I-related compositions and methods (USPTO 12116606).

Subjects
COMPLEMENT (Immunology), BLOOD proteins, LOW density lipoprotein receptors, PEPTIDES, PROTEOLYTIC enzymes
Abstract

A patent has been issued for complement factor I-related compositions and methods by Vertex Pharmaceuticals Incorporated. The patent discusses the role of Complement Factor I (CFI) in regulating the complement system by cleaving C4b and C3b proteins. The invention provides variants of CFI capable of modulating the complement system with improved characteristics compared to wild type CFI, such as increased activity or substrate specificity. The patent also describes fusion constructs involving CFI and half-life extenders for pharmaceutical compositions. [Extracted from the article]

Published
2024

4. "C3b Inactivating Polypeptide" in Patent Application Approval Process (USPTO 20240336675).

Abstract

A patent application for a C3b inactivating polypeptide has been filed by inventors from London, GB, with a focus on age-related macular degeneration (AMD). The polypeptide aims to bind to and inactivate C3b, a key player in the complement system that contributes to the pathogenesis of AMD. The invention includes various aspects such as nucleic acid encoding, vectors, cells, pharmaceutical compositions, and methods for treating or preventing diseases involving C3b. This research offers potential therapeutic avenues for conditions like AMD and other complement-related diseases. [Extracted from the article]

Published
2024

5. Hospital Italiano de Buenos Aires Reports Findings in Hemolytic Uremic Syndrome (Eculizumab as first-line treatment for patients with severe presentation of complement factor H antibody-mediated hemolytic uremic syndrome).

Subjects
COMPLEMENT factor H, BLOOD platelet disorders, COMPLEMENT (Immunology), HEMOLYTIC-uremic syndrome, BLOOD protein disorders
Abstract

A study conducted at Hospital Italiano de Buenos Aires in Argentina focused on the use of eculizumab as a first-line treatment for children with complement factor H antibody-mediated hemolytic uremic syndrome (HUS). The research involved four children aged 6-11 years old who showed improvement in hematological signs and kidney function after receiving eculizumab. The study suggested that a short course of eculizumab, along with immunosuppressive agents, may be effective in reversing thrombotic microangiopathy symptoms and improving kidney function in patients with severe FH antibody-mediated HUS. [Extracted from the article]

Published
2024

6. Truncated Complement Factor H Y402 Gene Therapy Cures C3 Glomerulonephritis.

Abstract

A recent preprint abstract discusses the potential of gene therapy to treat both age-related macular degeneration (AMD) and C3 glomerulonephritis (C3G). The study focused on using adeno-associated virus (AAV) delivery of truncated complement factor H (tCFH) to restore inhibition of the alternative pathway of complement and reverse C3G in a mouse model. The findings suggest that AAV-mediated tCFH replacement therapy could be developed for patients with C3G, as well as a gene augmentation therapy for patients with AMD. However, it is important to note that this preprint has not yet undergone peer review. [Extracted from the article]

Published
2024

7. Uppsala University Reports Findings in Complement C3b Inactivator Proteins (Model-based Interspecies Scaling for Predicting Human Pharmacokinetics of Cb 4332, a Complement Factor I Protein).

Abstract

A study conducted by Uppsala University in Sweden examined the pharmacokinetics of CB 4332, a complement factor I protein, using traditional and model-based approaches. The study found species-specific differences in elimination and observed the formation of anti-drug antibodies in rats and nonhuman primates. The researchers concluded that a once-weekly subcutaneous dose of 5 mg/kg would reach the efficacy target range for CB 4332 in humans. This research has been peer-reviewed and published in the Journal of Pharmaceutical Sciences. [Extracted from the article]

Published
2024

8. Localization of complement factor H gene expression and protein distribution in the mouse outer retina.

Author

Smit-McBride, Zeljka, Oltjen, Sharon L, Radu, Roxana A, Estep, Jason, Nguyen, Anthony T, Gong, Qizhi, and Hjelmeland, Leonard M

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Eye Disease and Disorders of Vision, Biotechnology, Genetics, Neurosciences, Amino Acid Sequence, Animals, Complement C3b Inactivator Proteins, Complement Factor H, Epithelial Cells, Female, Gene Expression, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Molecular Sequence Data, Organ Specificity, Photoreceptor Cells, Vertebrate, RNA, Messenger, Retinal Pigment Epithelium, Sequence Alignment, Sequence Homology, Amino Acid, Opthalmology and Optometry, Ophthalmology & Optometry, Ophthalmology and optometry
Abstract

PurposeTo determine the localization of complement factor H (Cfh) mRNA and its protein in the mouse outer retina.MethodsQuantitative real-time PCR (qPCR) was used to determine the expression of Cfh and Cfh-related (Cfhr) transcripts in the RPE/choroid. In situ hybridization (ISH) was performed using the novel RNAscope 2.0 FFPE assay to localize the expression of Cfh mRNA in the mouse outer retina. Immunohistochemistry (IHC) was used to localize Cfh protein expression, and western blots were used to characterize CFH antibodies used for IHC.ResultsCfh and Cfhr2 transcripts were detected in the mouse RPE/choroid using qPCR, while Cfhr1, Cfhr3, and Cfhrc (Gm4788) were not detected. ISH showed abundant Cfh mRNA in the RPE of all mouse strains (C57BL/6, BALB/c, 129/Sv) tested, with the exception of the Cfh(-/-) eye. Surprisingly, the Cfh protein was detected by immunohistochemistry in photoreceptors rather than in RPE cells. The specificity of the CFH antibodies was tested by western blotting. Our CFH antibodies recognized purified mouse Cfh protein, serum Cfh protein in wild-type C57BL/6, BALB/c, and 129/Sv, and showed an absence of the Cfh protein in the serum of Cfh(-/-) mice. Greatly reduced Cfh protein immunohistological signals in the Cfh(-/-) eyes also supported the specificity of the Cfh protein distribution results.ConclusionsOnly Cfh and Cfhr2 genes are expressed in the mouse outer retina. Only Cfh mRNA was detected in the RPE, but no protein. We hypothesize that the steady-state concentration of Cfh protein is low in the cells due to secretion, and therefore is below the detection level for IHC.

Published
2015

9. First Affiliated Hospital of Shandong First Medical University Researcher Releases New Data on Complement C3b Inactivator Proteins (Complement factor H in molecular regulation of angiogenesis).

Abstract

A new report discusses research on complement C3b inactivator proteins and their role in angiogenesis, the process of forming new capillaries from existing blood vessels. The study focuses on complement factor H (CFH), a plasma protein that inhibits the alternative pathway of the complement system. Dysfunction of CFH can lead to pro-angiogenic events and has been associated with age-related macular degeneration. The review summarizes the molecular mechanisms of CFH's anti-angiogenic effects and discusses the therapeutic potential of recombinant CFH protein in angiogenesis-related diseases. [Extracted from the article]

Published
2024

10. Flinders University Researcher Discusses Research in Dengue Hemorrhagic Fever (Dengue virus infection induces complement factor H but protein remains cell-associated, with changes intracellularly and in cell surface binding).

Subjects
COMPLEMENT factor H, DENGUE hemorrhagic fever, DENGUE viruses, VIRUS diseases, COMPLEMENT (Immunology), ECULIZUMAB
Abstract

A recent study conducted by researchers at Flinders University in Australia explored the mechanisms behind the decrease in the complement regulator, factor H (FH), during severe dengue infection. The researchers found that dengue virus (DENV) infection induces FH mRNA but not FH protein release. They also discovered that secreted molecules induce FH that remains intracellular and binds to cell surface heparan sulfate. This retention of FH in the local environment of infected cells may benefit the virus by preventing complement killing of cells and/or benefit the host by inhibiting heparan sulfate-mediated DENV infection. [Extracted from the article]

Published
2024

11. Researchers' Work from University of Gdansk Focuses on Lung Cancer (Elevated Expression of Complement Factor I In Lung Cancer Cells Associates With Shorter Survival-potentially Via Non-canonical Mechanism).

Abstract

A study conducted by researchers at the University of Gdansk in Poland focused on the expression of complement factor I (FI) in lung cancer cells and its association with patient outcomes. The researchers found that the intensity of FI expression did not correlate with various clinicopathological characteristics, but it was associated with progression-free survival, overall survival, and disease-specific survival. The study also revealed that FI may have a non-canonical role in lung cancer cells, influencing cellular physiology and contributing to poor prognosis. Further research is needed to understand the mechanisms behind this association. [Extracted from the article]

Published
2024

12. Ocular biomarker profiling after complement factor I gene therapy in geographic atrophy secondary to age-related macular degeneration (Updated June 15, 2024).

Abstract

A recent preprint abstract discusses the use of gene therapy in treating geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The study evaluated the effects of subretinal AAV2 complement factor I (CFI) gene therapy on complement biomarkers in ocular fluid samples from 28 subjects in a Phase I/II clinical trial. The results showed an increase in intact complement factor I (FI) levels post-treatment, but minimal changes in other complement proteins. The study suggests that the gene therapy may not have provided sufficient FI protein to effectively slow GA growth. Further research is needed to determine the optimal dose for future clinical development. [Extracted from the article]

Published
2024

13. CFHR1 involvement in bile duct carcinoma: Insights from a data mining study.

Author

Liu Y, Shen T, Liu J, Yu X, Li Q, Chen T, and Jiang T

Subjects
Humans, Biomarkers, Prognosis, Bile Ducts, Intrahepatic pathology, Tumor Microenvironment, Complement C3b Inactivator Proteins, Bile Duct Neoplasms genetics, Bile Duct Neoplasms diagnosis, Bile Duct Neoplasms pathology, Cholangiocarcinoma genetics
Abstract

The aim of this study is to investigate the role of CFHR1 in bile duct carcinoma (BDC) and its mechanism of action, and we hope that our analysis and research will contribute to a better understanding of cholangiocarcinoma (BDC) disease genesis, progression and the development of new therapeutic strategies. The prognostic receiver operating characteristic curve of CFHR1 was generated using survival ROC. The ROC curve for CFHR1 showed that there is a correlation between CFHR1 expression and clinicopathological parameters and has an impact on poor prognosis. STRING was used to predict the protein-protein interaction network of the identified genes, and the Microenvironment Cell Populations counter algorithm was used to analyze immune cell infiltration within the BDC. The combined analysis showed that CFHR1 was found to be upregulated in BDC tissues, along with a total of 20 related differentially expressed genes (DEGs) (8 downregulated and 12 upregulated genes). Also, the results showed that the expression of CFHR1 is correlated with immune cell infiltration in tumor and immune cell markers in BDC (P < 0.05). In addition, we have verified experimentally the biological function of CFHR1. These findings suggest that CFHR1 may be a prognostic marker and a potential therapeutic target for BDC. Information regarding the detailed roles of CFHR1 in BDC could be valuable for improving the diagnosis and treatment of this rare cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Published
2024
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14. Investigation of modifier genes within copy number variations in Rett syndrome

Author

Artuso, Rosangela, Papa, Filomena T, Grillo, Elisa, Mucciolo, Mafalda, Yasui, Dag H, Dunaway, Keith W, Disciglio, Vittoria, Mencarelli, Maria A, Pollazzon, Marzia, Zappella, Michele, Hayek, Giuseppe, Mari, Francesca, Renieri, Alessandra, LaSalle, Janine M, and Ariani, Francesca

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Pediatric, Neurosciences, Brain Disorders, Rare Diseases, Rett Syndrome, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, Blood Proteins, Chromatin Immunoprecipitation, Chromosomes, Human, Pair 1, Complement C3b Inactivator Proteins, Cytoskeletal Proteins, DNA Copy Number Variations, Female, Humans, Methyl-CpG-Binding Protein 2, Phenotype, copy number variants, modifier genes, Rett syndrome, Clinical Sciences, Genetics & Heredity, Clinical sciences
Abstract

MECP2 mutations are responsible for two different phenotypes in females, classical Rett syndrome and the milder Zappella variant (Z-RTT). We investigated whether copy number variants (CNVs) may modulate the phenotype by comparison of array-CGH data from two discordant pairs of sisters and four additional discordant pairs of unrelated girls matched by mutation type. We also searched for potential MeCP2 targets within CNVs by chromatin immunopreceipitation microarray (ChIP-chip) analysis. We did not identify one major common gene/region, suggesting that modifiers may be complex and variable between cases. However, we detected CNVs correlating with disease severity that contain candidate modifiers. CROCC (1p36.13) is a potential MeCP2 target, in which a duplication in a Z-RTT and a deletion in a classic patient were observed. CROCC encodes a structural component of ciliary motility that is required for correct brain development. CFHR1 and CFHR3, on 1q31.3, may be involved in the regulation of complement during synapse elimination, and were found to be deleted in a Z-RTT but duplicated in two classic patients. The duplication of 10q11.22, present in two Z-RTT patients, includes GPRIN2, a regulator of neurite outgrowth and PPYR1, involved in energy homeostasis. Functional analyses are necessary to confirm candidates and to define targets for future therapies.

Published
2011

15. Findings from Institute of Biomedical Research Yields New Findings on Age-Related Macular Degeneration (C-reactive Protein-complement Factor H Axis As a Biomarker of Activity In Early and Intermediate Age-related Macular Degeneration).

Abstract

A recent study conducted in Barcelona, Spain, investigated the serum levels of complement Factor H (FH), monomeric C-Reactive Protein (mCRP), and pentameric C-Reactive Protein (pCRP) in patients with age-related macular degeneration (AMD). The study found that patients with intermediate AMD had significantly lower FH levels compared to healthy controls, and FH levels below 200 μg/mL were associated with certain changes in the fundoscopy. While no differences were observed in pCRP and mCRP levels, women had a higher detection rate of mCRP than men. The study suggests that these serum biomarkers may indicate an underlying systemic inflammatory process in early/intermediate AMD patients. [Extracted from the article]

Published
2024

16. Researchers from Pirbright Institute Detail Findings in Influenza A Virus (Mapping the interaction sites of human and avian influenza A viruses and complement factor H).

Abstract

Researchers from the Pirbright Institute in the United Kingdom have conducted a study on the interaction between human and avian influenza A viruses and complement factor H (FH), a negative regulator of the complement alternative pathway. They found that FH can bind directly to both human and avian influenza A viruses, and this interaction is mediated by the surface glycoprotein haemagglutinin (HA) on the viruses. The study suggests that the interaction between FH and influenza A viruses may impede the initial entry of certain strains of the virus, but its impact on viral replication is strain-specific. Further research is needed to understand the significance of this interaction for the virus and the host. [Extracted from the article]

Published
2024

17. Patent Application Titled "Fluorescence Detection of Circulating Cell Free DNA Including Within Extracellular Vesicles in Biospecimens and Liquid Biopsies" Published Online (USPTO 20240102995).

Abstract

The patent application titled "Fluorescence Detection of Circulating Cell Free DNA Including Within Extracellular Vesicles in Biospecimens and Liquid Biopsies" outlines a method for detecting circulating cell-free DNA (ccf-DNA) in liquid biopsies. By staining extracellular vesicles (EVs) in a biological sample with a DNA staining dye, the presence of DNA, including mitochondrial DNA (mtDNA), can be detected. This method has potential applications in assessing tissue/organ injury severity, monitoring disease progression, and evaluating the response to therapeutic interventions. It can be used in various settings, such as emergency rooms, critical care settings, or at home, and has the potential to diagnose lung adenocarcinoma, traumatic brain injury, brain trauma, concussion, diseases of oxidative stress, and viral infections. The patent application provides a comprehensive list of proteins that can be measured and used in an algorithm to determine the presence and severity of traumatic brain injury. [Extracted from the article]

Published
2024

19. Cooch Behar Panchanan Barma University Researchers Publish New Data on Complement C3b Inactivator Proteins (Protective role of complement factor H against the development of preeclampsia).

Abstract

Researchers from Cooch Behar Panchanan Barma University in West Bengal, India have published a study on complement C3b inactivator proteins and their role in pregnancy, specifically in relation to preeclampsia. The study found that complement factor H (FH), a negative regulator of complement activation, is expressed differently in placental tissues of preeclampsia patients compared to normal placental tissue. FH appears to play a homeostatic role during pregnancy and may have a protective effect against the development of preeclampsia. The study suggests that complement inhibitors at the feto-maternal interface could prevent inappropriate complement activation and protect the fetus. [Extracted from the article]

Published
2024

20. Gene deletions in complement factor H related protein gene locus and kidney transplantation.

Abstract

A recent study found that a homozygous deletion in the complement factor H related (CFHR) protein gene locus may predispose kidney transplant patients to allograft rejection. The researchers confirmed that patients with this deletion had various sizes of deletions that included the entire CFHR1 gene. The lack of CFHR1 protein in patient plasma samples was also observed. Proteomics analysis showed that the deletion-tagging allele was associated with altered expression of CFH/CFHR proteins. Further studies are needed to understand the role of these proteins in transplantation outcomes. [Extracted from the article]

Published
2024

21. De novo systemic atypical hemolytic uremic syndrome in an ABO-incompatible living kidney transplant recipient with a novel pathogenic CFHR1 gene mutation successfully treated with eculizumab: a case report

Author

Dawei, Li, Wei, Wang, Ruoyang, Chen, Jiqiu, Wen, and Ming, Zhang

Subjects
Male, Nephrology, Mutation, Complement C3b Inactivator Proteins, Humans, Middle Aged, Antibodies, Monoclonal, Humanized, Kidney Transplantation, Atypical Hemolytic Uremic Syndrome
Abstract

De novo systemic atypical hemolytic uremic syndrome (aHUS) post-kidney transplant is an uncommon entity associated with unfavorable outcome. We herein report a case of systemic and fulminant de novo aHUS accompanied by heart and respiratory failure in a 48-year-old male receiving ABO-incompatible living-related kidney transplant who was successfully treated with the anti-C5 monoclonal antibody eculizumab with complete recovery of allograft function. Genetic testing demonstrated a novel pathogenic heterozygous complement factor H-related 1 gene mutation in both the donor and the recipient. Our study highlights the high risks of post-transplant aHUS due to the complement gene mutations in both donor and recipient in living-related transplantation. Early intervention with eculizumab may be effective for reversing systemic aHUS in kidney transplant recipients.

Published
2022
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22. Duke University School of Medicine Researchers Publish New Data on Cancer (Complement factor H: a novel innate immune checkpoint in cancer immunotherapy).

Abstract

Duke University School of Medicine researchers have published a new report on cancer, focusing on the role of complement factor H (CFH) as an innate immune checkpoint in cancer immunotherapy. The researchers explain that CFH, which is primarily known for inhibiting the alternative pathway of the complement system, has been identified as an important factor in cancer's ability to evade immune recognition and create an immunosuppressive tumor microenvironment. The report explores the molecular mechanisms, interactions with immune cells, clinical implications, and potential therapeutic applications of CFH in cancer control. The researchers also discuss the challenges and opportunities of targeting CFH in cancer immunotherapy. [Extracted from the article]

Published
2024

23. Researchers Submit Patent Application, "Methods For Treating Inflammatory Ocular Diseases With Complement Factor H", for Approval (USPTO 20240024416).

Subjects
COMPLEMENT factor H, PATENT applications, PATENTS, INVENTORS, RESEARCH personnel, MACULAR degeneration, INTANGIBLE property, COMPLEMENT (Immunology)
Abstract

A patent application has been submitted for a method of treating inflammatory ocular diseases, specifically age-related macular degeneration (AMD), using complement factor H (CFH) protein. The application provides specific dosage regimens for administering CFH protein to patients with AMD and other inflammatory ocular diseases. The treatment aims to slow disease progression and reduce severity, and can be assessed using visual acuity scores and imaging techniques. The application also acknowledges the need for new treatments for AMD, which is a leading cause of legal blindness in Western societies. For more information, please refer to the full patent application. [Extracted from the article]

Published
2024

24. University of Utah Researchers Publish New Study Findings on Age-Related Macular Degeneration (Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression).

Abstract

A recent study conducted by researchers at the University of Utah found that levels of complement factor H-related 4 protein (FHR-4) do not influence susceptibility to age-related macular degeneration (AMD) or its progression. The researchers analyzed two cohorts consisting of over 14,000 controls and 20,000 cases and determined that FHR-4 variation is not independently associated with AMD. Therefore, modulating FHR-4 is unlikely to be an effective therapeutic strategy for AMD. This study provides valuable insights into the understanding of AMD and potential treatment options. [Extracted from the article]

Published
2024

25. An Infant Case of Streptococcus Pneumoniae-Associated Thrombotic Microangiopathy with Heterozygous CFI Mutation and CFHR3-CFHR1 Deletion

Author

Yuji, Matsumoto, Yohei, Ikezumi, Tomomi, Kondoh, Katsuyuki, Yokoi, Yoko, Nakajima, Naonori, Kumagai, Takema, Kato, Hiroki, Kurahashi, and Tetsuya, Ito

Subjects
Male, Streptococcus pneumoniae, Complement Factor I, Thrombotic Microangiopathies, Mutation, Complement C3b Inactivator Proteins, Infant, Humans, Antibodies, Monoclonal, Blood Proteins, Atypical Hemolytic Uremic Syndrome
Abstract

Thrombotic microangiopathy (TMA) is a disease that causes organ damage due to microvascular hemolytic anemia, thrombocytopenia, and microvascular platelet thrombosis. Streptococcus pneumoniae-associated TMA (spTMA) is a rare complication of invasive pneumococcal infection. In addition, atypical hemolytic uremic syndrome (aHUS) is TMA associated with congenital or acquired dysregulation of complement activation. We report the case of a nine-month-old boy with refractory nephrotic syndrome complicated by spTMA in the setting of heterozygous complement factor-I (CFI) gene mutation and CFHR3-CFHR1 deletion. He repeatedly developed thrombocytopenia, anemia with schistocytes, hypocomplementemia, and abnormal coagulation triggered by infection, which manifested clinically with convulsions and an intraperitoneal hematoma. Eculizumab (a monoclonal humanized anti-C5 antibody) provided transient symptomatic benefit including improvement in thrombocytopenia; however, he developed unexplained cardiac arrest and was declared brain dead a few days later. In this report, we highlight the diagnostic challenges of this case and the causal relationship between spTMA and complement abnormalities and consider the contribution of heterozygous mutation of CFI and CFHR3-CFHR1 deletion.

Published
2022

26. Benefits of genetic and immunohistochemical markers in understanding abnormalities in aging retina

Author

Delia Maria, Ormenişan and Angela, Borda

Subjects
Aging, Genotype, Complement C3b Inactivator Proteins, Humans, DNA, Biomarkers, Retina, Aged
Abstract

The aim of the study was to better understand the interplay between genetic factors and the aging process in the human retina through mapping complement factor H (CFH) and related proteins. Two human eyes, from 92- and 64-year-old donors, were genotyped for the expression of CFH-related 1 (CFHR1) and CFH-related 3 (CFHR3) genes. Deoxyribonucleic acid (DNA) was extracted and analyzed for concentration and purity with a spectrophotometer, at 260 nm. The results showed a DNA concentration of 469.17 ng∕μL in the aged retina and of 399.20 ng∕μL in the younger one. Through polymerase chain reaction (PCR) genotyping, the DNA CFHR1 and CFHR3 were visible as bands of 175 bp and 181 bp. Immunohistochemistry by immunofluorescence method was used with a panel of specific antibodies for CFH, CFHR1, CFHR3 and GFAP, a marker for Müller cells. All the samples were examined, and images captured using confocal microscopy. In the younger retina, CFH was localized in the inner plexiform layer and below the outer nuclear layer, while in the aged retina, it was found in the photoreceptors. CFH was also detected in the choriocapillaris and within the end-feet of the Müller cells. Our controls showed autofluorescence of the retinal pigment epithelium shedding light on a false positive CFH immunostaining of this layer. GFAP immunoreactivity highlighted an increased gliosis within the aged retina. CFHR3 signal was found in the microglia, while CFHR1 was detected in the choriocapillaris. In summary, underpinning the expression of these components can show the potential involvement of these modulators in implementing new treatment strategies.

Published
2022

27. Researchers at Zealand University Hospital Publish New Data on Age-Related Macular Degeneration (Complement factor H Y402H polymorphism results in diminishing CD4+ T cells and increasing C-reactive protein in plasma).

Subjects
COMPLEMENT factor H, MACULAR degeneration, BLOOD proteins, C-reactive protein, T cells, ECULIZUMAB
Abstract

A new report from Zealand University Hospital discusses research findings on age-related macular degeneration (AMD), a common cause of visual loss among the elderly. The study focuses on the genetic variants in the gene encoding complement factor H (CFH) and their link to low-grade inflammation. The research found that individuals with the CFH Y402H at-risk polymorphism had higher levels of C-reactive protein (CRP) and lower proportions of CD4+ T cells. These findings suggest that decreased complement regulation leads to changes in the immune system that precede the development of AMD. [Extracted from the article]

Published
2023

28. Fibrinogen and complement factor H: The two crucial markers of Parkinson's disease with cognitive impairment.

Abstract

A recent study investigated the potential biomarkers for Parkinson's disease with cognitive impairment (PDCI) by analyzing cerebrospinal fluid (CSF) samples from PD patients. The study found elevated levels of fibrinogen and complement factor H (CFAH) in the CSF of PDCI patients. To further understand the role of these proteins, the researchers injected native fibrinogen and recombinant CFAH into mice and observed motor and cognitive deficits, as well as neuroanatomical changes similar to PD pathology. The study suggests that fibrinogen and CFAH may serve as potential biomarkers for PDCI. However, it is important to note that this study has not yet undergone peer review. [Extracted from the article]

Published
2023

29. Research from Linnaeus University Provides New Data on Complement C3b Inactivator Proteins (Functional evaluation of complement factor I variants by immunoassays and SDS-PAGE).

Abstract

A recent study conducted at Linnaeus University in Kalmar, Sweden, focused on complement C3b inactivator proteins, which play a crucial role in regulating the complement system. The researchers evaluated eight genetic variants of complement factor I (FI) found in patients and assessed their co-factor activity using various analytical assays. The study found that mutations in certain domains of FI led to reduced protease activity, while others did not significantly affect its function. The results highlight the importance of using multiple methods and co-factors to accurately assess the impact of mutations in FI and provide new insights for diagnostic tools in evaluating these mutations. [Extracted from the article]

Published
2023

30. Researchers at Newcastle University Release New Data on Age-Related Macular Degeneration (Rare Complement Factor I Variants Associated With Reduced Macular Thickness and Age-related Macular Degeneration In the Uk Biobank).

Abstract

Newcastle upon Tyne, United Kingdom, Europe, Age-Related Macular Degeneration, Biological Factors, Biological Pigments, Blood Proteins, Complement Factor I, Complement C3b Inactivator Proteins, Enzymes and Coenzymes, Eye Diseases and Conditions, Genetics, Health and Medicine, Immunology, Immunoproteins, Macular Degeneration, Peptide Hydrolases, Retinal Degeneration, Retinal Diseases and Conditions, Retinal Pigments, Risk and Prevention, Serine Endopeptidases, Complement System Proteins Keywords: Newcastle upon Tyne; United Kingdom; Europe; Age-Related Macular Degeneration; Biological Factors; Biological Pigments; Blood Proteins; Complement C3b Inactivator Proteins; Complement Factor I; Complement System Proteins; Enzymes and Coenzymes; Eye Diseases and Conditions; Genetics; Health and Medicine; Immunology; Immunoproteins; Macular Degeneration; Peptide Hydrolases; Retinal Degeneration; Retinal Diseases and Conditions; Retinal Pigments; Risk and Prevention; Serine Endopeptidases EN Newcastle upon Tyne United Kingdom Europe Age-Related Macular Degeneration Biological Factors Biological Pigments Blood Proteins Complement C3b Inactivator Proteins Complement Factor I Complement System Proteins Enzymes and Coenzymes Eye Diseases and Conditions Genetics Health and Medicine Immunology Immunoproteins Macular Degeneration Peptide Hydrolases Retinal Degeneration Retinal Diseases and Conditions Retinal Pigments Risk and Prevention Serine Endopeptidases 1823 1823 1 10/30/23 20231103 NES 231103 2023 NOV 3 (NewsRx) -- By a News Reporter-Staff News Editor at Genomics & Genetics Weekly -- Investigators publish new report on Eye Diseases and Conditions - Age-Related Macular Degeneration. [Extracted from the article]

Published
2023

32. Study Results from Chulalongkorn University in the Area of Hemolytic Uremic Syndrome Reported (Complement Factor I Gene Variant In an Atypical Hemolytic Uremic Syndrome Triggered By Hypereosinophilia Syndrome).

Subjects
HEMOLYTIC-uremic syndrome, GENETIC variation, BLOOD platelet disorders, COMPLEMENT (Immunology), THROMBOTIC thrombocytopenic purpura, BLOOD protein disorders
Abstract

Bangkok, Thailand, Asia, Blood Platelet Disorders, Blood Proteins, Complement C3b Inactivator Proteins, Complement Factor I, Complement System Proteins, Enzymes and Coenzymes, Genetics, Health and Medicine, Hematologic Diseases and Conditions, Hematology, Hemic and Lymphatic Diseases and Conditions, Hemolytic, Hemolytic Uremic Syndrome, Immunology, Immunoproteins, Kidney Diseases and Conditions, Peptide Hydrolases, Serine Endopeptidases, Thrombocytopenia, Thrombotic Microangiopathies, Hemolytic Anemia Keywords: Bangkok; Thailand; Asia; Blood Platelet Disorders; Blood Proteins; Complement C3b Inactivator Proteins; Complement Factor I; Complement System Proteins; Enzymes and Coenzymes; Genetics; Health and Medicine; Hematologic Diseases and Conditions; Hematology; Hemic and Lymphatic Diseases and Conditions; Hemolytic; Hemolytic Anemia; Hemolytic Uremic Syndrome; Immunology; Immunoproteins; Kidney Diseases and Conditions; Peptide Hydrolases; Serine Endopeptidases; Thrombocytopenia; Thrombotic Microangiopathies EN Bangkok Thailand Asia Blood Platelet Disorders Blood Proteins Complement C3b Inactivator Proteins Complement Factor I Complement System Proteins Enzymes and Coenzymes Genetics Health and Medicine Hematologic Diseases and Conditions Hematology Hemic and Lymphatic Diseases and Conditions Hemolytic Hemolytic Anemia Hemolytic Uremic Syndrome Immunology Immunoproteins Kidney Diseases and Conditions Peptide Hydrolases Serine Endopeptidases Thrombocytopenia Thrombotic Microangiopathies 728 728 1 10/03/23 20231003 NES 231003 2023 OCT 2 (NewsRx) -- By a News Reporter-Staff News Editor at Hematology Week -- Research findings on Kidney Diseases and Conditions - Hemolytic Uremic Syndrome are discussed in a new report. [Extracted from the article]

Published
2023

33. New Findings Reported from Shandong University Describe Advances in Complement C3b Inactivator Proteins (Complement Factor H Inhibits Endothelial Cell Migration Through Suppression of Stat3 Signaling).

Abstract

Keywords for this news article include: Shandong, People's Republic of China, Asia, Angiogenesis, Beta-Globulins, Blood Proteins, Complement C3b Inactivator Proteins, Complement Factor H, Complement System Proteins, Drugs and Therapies, Endothelial Cells, Immunology, Immunoproteins, Proteins, Shandong University. Keywords: Shandong; People's Republic of China; Asia; Angiogenesis; Beta-Globulins; Blood Proteins; Complement C3b Inactivator Proteins; Complement Factor H; Complement System Proteins; Drugs and Therapies; Endothelial Cells; Immunology; Immunoproteins; Proteins EN Shandong People's Republic of China Asia Angiogenesis Beta-Globulins Blood Proteins Complement C3b Inactivator Proteins Complement Factor H Complement System Proteins Drugs and Therapies Endothelial Cells Immunology Immunoproteins Proteins 1330 1330 1 08/28/23 20230901 NES 230901 2023 SEP 1 (NewsRx) -- By a News Reporter-Staff News Editor at Gene Therapy Weekly -- Research findings on Proteins - Complement C3b Inactivator Proteins are discussed in a new report. [Extracted from the article]

Published
2023

34. Anti-factor H antibody and its role in atypical hemolytic uremic syndrome

Author

Rupesh Raina, Guneive Mangat, Gordon Hong, Raghav Shah, Nikhil Nair, Brian Abboud, Sumedha Bagga, and Sidharth Kumar Sethi

Subjects
Plasma Exchange, Complement Factor H, Immunology, Complement C3b Inactivator Proteins, Humans, Immunology and Allergy, Blood Proteins, Complement System Proteins, Acute Kidney Injury, Antibodies, Atypical Hemolytic Uremic Syndrome
Abstract

Atypical hemolytic uremic syndrome (aHUS) an important form of a thrombotic microangiopathy (TMA) that can frequently lead to acute kidney injury (AKI). An important subset of aHUS is the anti-factor H associated aHUS. This variant of aHUS can occur due to deletion of the complement factor H genes, CFHR1 and CFHR3, along with the presence of anti-factor H antibodies. However, it is a point of interest to note that not all patients with anti-factor H associated aHUS have a CFHR1/R3 deletion. Factor-H has a vital role in the regulation of the complement system, specifically the alternate pathway. Therefore, dysregulation of the complement system can lead to inflammatory or autoimmune diseases. Patients with this disease respond well to treatment with plasma exchange therapy along with Eculizumab and immunosuppressant therapy. Anti-factor H antibody associated aHUS has a certain genetic predilection therefore there is focus on further advancements in the diagnosis and management of this disease. In this article we discuss the baseline characteristics of patients with anti-factor H associated aHUS, their triggers, various treatment modalities and future perspectives.

Published
2022
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35. Unraveling structural rearrangements of the CFH gene cluster in atypical hemolytic uremic syndrome patients using molecular combing and long-fragment targeted sequencing

Author

Nikolai Tschernoster, Florian Erger, Patrick R. Walsh, Bairbre McNicholas, Margareta Fistrek, Sandra Habbig, Anna-Lena Schumacher, Kat Folz-Donahue, Christian Kukat, Mohammad R. Toliat, Christian Becker, Holger Thiele, David Kavanagh, Peter Nürnberg, Bodo B. Beck, and Janine Altmüller

Subjects
Haplotypes, Complement Factor H, Multigene Family, Complement C3b Inactivator Proteins, Humans, Molecular Medicine, Pilot Projects, Technology Platforms, eye diseases, Atypical Hemolytic Uremic Syndrome, Pathology and Forensic Medicine
Abstract

Complement factor H (CFH) and its related proteins have an essential role in regulating the alternative pathway of the complement system. Mutations and structural variants (SVs) of the CFH gene cluster, consisting of CFH and its five related genes (CFHR1-5), have been reported in renal pathologies as well as in complex immune diseases like age-related macular degeneration and systemic lupus erythematosus. SV analysis of this cluster is challenging because of its high degree of sequence homology. Following first-line next-generation sequencing gene panel sequencing, we applied Genomic Vision's Molecular Combing Technology to detect and visualize SVs within the CFH gene cluster and resolve its structural haplotypes completely. This approach was tested in three patients with atypical hemolytic uremic syndrome and known SVs and 18 patients with atypical hemolytic uremic syndrome or complement factor 3 glomerulopathy with unknown CFH gene cluster haplotypes. Three SVs, a CFH/CFHR1 hybrid gene in two patients and a rare heterozygous CFHR4/CFHR1 deletion in trans with the common CFHR3/CFHR1 deletion in a third patient, were newly identified. For the latter, the breakpoints were determined using a targeted enrichment approach for long DNA fragments (Samplix Xdrop) in combination with Oxford Nanopore sequencing. Molecular combing in addition to next-generation sequencing was able to improve the molecular genetic yield in this pilot study. This (cost-)effective approach warrants validation in larger cohorts with CFH/CFHR-associated disease.

Published
2022

36. Factor H–Related Protein 1 Drives Disease Susceptibility and Prognosis in C3 Glomerulopathy

Author

Márquez-Tirado, Bárbara, Gutiérrez-Tenorio, Josué, Tortajada, Agustín, Lucientes Continente, Laura, Caravaca-Fontán, Fernando, Malik, Talat H., Roldán Montero, Raquel, Elías, Sandra, Saiz Gonzalez, Ana, Fernández-Juarez, Gema, Sánchez-Corral, Pilar, Pickering, Matthew C., Praga, Manuel, Rodríguez de Córdoba, Santiago, Goicoechea de Jorge, Elena, Ministerio de Ciencia e Innovación (España), European Commission, Comunidad de Madrid, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Gutiérrez-Tenorio, Josué [0000-0001-8590-5455], Tortajada, Agustín [0000-0002-2131-2594], Lucientes, Laura [0000-0001-5596-370X], Caravaca-Fontán, Fernando [0000-0002-5830-9663], Saiz Gonzalez, Ana [0000-0001-7110-450X], Fernández-Juárez, Gema [0000-0001-6641-7763], Sánchez-Corral, Pilar [0000-0003-4212-1233], Pickering, Matthew C. [0000-0002-1153-0192], Praga, Manuel [0000-0001-9270-1071], Rodríguez de Córdoba, Santiago [0000-0001-6401-1874], Goicoechea de Jorge, Elena [0000-0002-4978-2483], Gutiérrez-Tenorio, Josué, Tortajada, Agustín, Lucientes, Laura, Caravaca-Fontán, Fernando, Saiz Gonzalez, Ana, Fernández-Juárez, Gema, Sánchez-Corral, Pilar, Pickering, Matthew C., Praga, Manuel, Rodríguez de Córdoba, Santiago, and Goicoechea de Jorge, Elena

Subjects
Glomerular disease, Disease susceptibility, DNA Copy Number Variations, Factor H-related protein 1, Complement, Genetic renal disease, Glomerulonephritis, IGA, General Medicine, Blood Proteins, Complement C3, Prognosis, Basic Research, Nephrology, Complement Factor H, Complement C3b Inactivator Proteins, Humans, C3 glomerulopathy, Disease Susceptibility
Abstract

17 p.-8 fig., Background: C3 glomerulopathy (C3G) is a heterogeneous group of chronic renal diseases characterized predominantly by glomerular C3 deposition and complement dysregulation. Mutations in factor H-related (FHR) proteins resulting in duplicated dimerization domains are prototypical of C3G, although the underlying pathogenic mechanism is unclear., Methods: Using in vitro and in vivo assays, we performed extensive characterization of an FHR-1 mutant with a duplicated dimerization domain. To assess the FHR-1 mutant's association with disease susceptibility and renal prognosis, we also analyzed CFHR1 copy number variations and FHR-1 plasma levels in two Spanish C3G cohorts and in a control population., Results: Duplication of the dimerization domain conferred FHR-1 with an increased capacity to interact with C3-opsonized surfaces, which resulted in an excessive activation of the alternative pathway. This activation does not involve C3b binding competition with factor H. These findings support a scenario in which mutant FHR-1 binds to C3-activated fragments and recruits native C3 and C3b; this leads to formation of alternative pathway C3 convertases, which increases deposition of C3b molecules, overcoming FH regulation. This suggests that a balanced FHR-1/FH ratio is crucial to control complement amplification on opsonized surfaces. Consistent with this conceptual framework, we show that the genetic deficiency of FHR-1 or decreased FHR-1 in plasma confers protection against developing C3G and associates with better renal outcome., Conclusions: Our findings explain how FHR-1 mutants with duplicated dimerization domains result in predisposition to C3G. They also provide a pathogenic mechanism that may be shared by other diseases, such as IgA nephropathy or age-related macular degeneration, and identify FHR-1 as a potential novel therapeutic target in C3G., E. Goicoechea de Jorge is supported by Ministerio de Ciencia e Innovación grant RTI2018-095955-B-100 and the European Union’s Horizon 2020 Framework Programme grant 899163. J. Gutiérrez-Tenorio is supported by Ministerio de Ciencia e Innovación grant BES-2015-073833. L. Lucientes Continente is supported by the Autonomous Region of Madrid grant S2017/BMD-3673. G. Fernández-Juarez, P. Sánchez-Corral, B. Márquez-Tirado, and M. Praga are supported by the Instituto de Salud Carlos III and the European Union’s European Regional Development Fund grants PI19/01695, PI19/00970, and PI19/01624, respectively. M.C. Pickering is a Wellcome Trust Senior Fellow in Clinical Science (212252/Z/18/Z). S. Rodríguez de Córdoba is supported by the Ministerio de Economía y Competitividad grant PID2019-104912RB-100 and Autonomous Region of Madrid grant S2017/BMD-3673.

Published
2022

37. Copy number variation analysis using next-generation sequencing identifies the

Author

Joonhong, Park, Ho-Young, Yhim, Kyung Pyo, Kang, Tae Won, Bae, and Yong Gon, Cho

Subjects
DNA Copy Number Variations, Complement Factor H, Complement C3b Inactivator Proteins, High-Throughput Nucleotide Sequencing, Humans, Female, Genetic Predisposition to Disease, Blood Proteins, Middle Aged, Atypical Hemolytic Uremic Syndrome
Abstract

Atypical hemolytic uremic syndrome (aHUS) is characterized by a triad of thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure resulting from platelet thrombi in the microcirculation of the kidney and other organs, in the absence of a preceding diarrheal illness. This report describes a case in which copy number variation (CNV) analysis using next-generation sequencing (NGS) identified theA 49-year-old Korean female was diagnosed with aHUS based on clinical findings, including schistocytes in peripheral blood and marked thrombocytopenia, suggesting the presence of thrombotic microangiopathy, elevated serum lactate dehydrogenase, and acute kidney injury. Sequence variants and CNV generated from NGS data were estimated to determine if there was a potential genetic cause. Multiplex ligation-dependent probe amplification (MLPA) was conducted to confirm theNo known or novel pathogenic single nucleotide variant or small insertion/deletion that would be predicted to have damaging effects that could lead to aHUS were identified. However, CNV analysis of NGS data identified the heterozygousWe genetically diagnosed a Korean woman harboring a heterozygous

Published
2022

38. Complement Factor H-Related Proteins FHR1 and FHR5 Interact With Extracellular Matrix Ligands, Reduce Factor H Regulatory Activity and Enhance Complement Activation

Author

Alexandra Papp, Krisztián Papp, Barbara Uzonyi, Marcell Cserhalmi, Ádám I. Csincsi, Zsóka Szabó, Zsófia Bánlaki, David Ermert, Zoltán Prohászka, Anna Erdei, Viviana P. Ferreira, Anna M. Blom, and Mihály Józsi

Subjects
Inflammation, Complement Factor H, Immunology, Complement C3b Inactivator Proteins, Humans, Immunology and Allergy, Complement System Proteins, Ligands, Complement Activation, Extracellular Matrix
Abstract

Components of the extracellular matrix (ECM), when exposed to body fluids may promote local complement activation and inflammation. Pathologic complement activation at the glomerular basement membrane and at the Bruch’s membrane is implicated in renal and eye diseases, respectively. Binding of soluble complement inhibitors to the ECM, including factor H (FH), is important to prevent excessive complement activation. Since the FH-related (FHR) proteins FHR1 and FHR5 are also implicated in these diseases, our aim was to study whether these FHRs can also bind to ECM components and affect local FH activity and complement activation. Both FH and the FHRs showed variable binding to ECM components. We identified laminin, fibromodulin, osteoadherin and PRELP as ligands of FHR1 and FHR5, and found that FHR1 bound to these ECM components through its C-terminal complement control protein (CCP) domains 4-5, whereas FHR5 boundviaits middle region, CCPs 3-7. Aggrecan, biglycan and decorin did not bind FH, FHR1 and FHR5. FHR5 also bound to immobilized C3b, a model of surface-deposited C3b,viaCCPs 3-7. By contrast, soluble C3, C3(H2O), and the C3 fragments C3b, iC3b and C3d bound to CCPs 8-9 of FHR5. Properdin, which was previously described to bindviaCCPs 1-2 to FHR5, did not bind in its physiologically occurring serum forms in our assays. FHR1 and FHR5 inhibited the binding of FH to the identified ECM proteins in a dose-dependent manner, which resulted in reduced FH cofactor activity. Moreover, both FHR1 and FHR5 enhanced alternative complement pathway activation on immobilized ECM proteins when exposed to human serum, resulting in the increased deposition of C3-fragments, factor B and C5b-9. Thus, our results identify novel ECM ligands of FH family proteins and indicate that FHR1 and FHR5 are competitive inhibitors of FH on ECM and, when bound to these ligands, they may enhance local complement activation and promote inflammation under pathological conditions.

Published
2022
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39. [Untitled]

Author

Paulo Ornellas, Antonio Augusto Ornellas, Clizia Chinello, Erica Gianazza, Veronica Mainini, Marta Cazzaniga, Denise Abreu Pereira, Vanessa Sandim, Ana Sheila Cypriano, Leandro Koifman, Paulo Cesar Barbosa da Silva, Gilda Alves, and Fulvio Magni

Subjects
Penis, Penis Cancer, Carcinoma, Squamous Cell, Plasma, Proteomics, Complement C3b Inactivator Proteins, Diseases of the genitourinary system. Urology, RC870-923
Abstract

PurposeTo investigate the use of ClinProt technique to identify cancer markers in plasma of patients suffering from squamous cell carcinoma of the penis (SCCP).Materials and MethodsPlasma of 36 healthy subjects and 25 patients with penile carcinoma who underwent surgical treatment between June 2010 and June 2011 was collected and analyzed by the ClinProt/MALDI/ToF technique. Then the peptides were identified from the C8 MB eluted fraction of patients' and control subjects' plasma by LIFT MS/MS.ResultsA cluster of 2 peptides (A=m/z 1897.22 ± 9 Da and B=m/z 2021.99 ± 9 Da) was able to discriminate patients from control subjects. Cross validation analysis using the whole casuistic showed 62.5% and 86.76% sensitivity and specificity, respectively. The cluster also showed very high sensitivity (100%) and specificity (97%) for SCCP patients that died due to the disease. Furthermore, patients with lymph node involvement presented sensitivity and specificity of 80% and 97%, respectively. These two peptides were identified by the proteomic approach based on a MALDI-TOF/TOF as fragments of C3 (m/z 1896.17) and C4a/b (m/z 2021.26) complement proteins.ConclusionsThe results showed that as the disease progresses, the fragments C3 and C4 A/B are less expressed in comparison with healthy subjects. These results may be useful as prognostic tools.

Published
2012

40. Downregulation of C3 and C4A/B complement factor fragments in plasma from patients with squamous cell carcinoma of the penis

Author

Paulo Ornellas, Antonio Augusto Ornellas, Clizia Chinello, Erica Gianazza, Veronica Mainini, Marta Cazzaniga, Denise Abreu Pereira, Vanessa Sandim, Ana Sheila Cypriano, Leandro Koifman, Paulo Cesar Barbosa da Silva, Gilda Alves, and Fulvio Magni

Subjects
Penis, Penis Cancer, Carcinoma, Squamous Cell, Plasma, Proteomics, Complement C3b Inactivator Proteins, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Purpose To investigate the use of ClinProt technique to identify cancer markers in plasma of patients suffering from squamous cell carcinoma of the penis (SCCP). Materials and Methods Plasma of 36 healthy subjects and 25 patients with penile carcinoma who underwent surgical treatment between June 2010 and June 2011 was collected and analyzed by the ClinProt/MALDI/ToF technique. Then the peptides were identified from the C8 MB eluted fraction of patients' and control subjects' plasma by LIFT MS/MS. Results A cluster of 2 peptides (A=m/z 1897.22 ± 9 Da and B=m/z 2021.99 ± 9 Da) was able to discriminate patients from control subjects. Cross validation analysis using the whole casuistic showed 62.5% and 86.76% sensitivity and specificity, respectively. The cluster also showed very high sensitivity (100%) and specificity (97%) for SCCP patients that died due to the disease. Furthermore, patients with lymph node involvement presented sensitivity and specificity of 80% and 97%, respectively. These two peptides were identified by the proteomic approach based on a MALDI-TOF/TOF as fragments of C3 (m/z 1896.17) and C4a/b (m/z 2021.26) complement proteins. Conclusions The results showed that as the disease progresses, the fragments C3 and C4 A/B are less expressed in comparison with healthy subjects. These results may be useful as prognostic tools.

Published
2012
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41. Ockham’s razor defeated: about two atypical cases of hemolytic uremic syndrome

Author

Alice Brehon, Patricia Senet, Yosu Luque, Inna Mohamadou, Chloe Schwarz, Lara Zafrani, Cyril Mousseaux, Véronique Frémeaux-Bacchi, Patricia Mariani, David Buob, Cédric Rafat, and Eric Rondeau

Subjects
Male, 0301 basic medicine, Physiopathology, 030232 urology & nephrology, Disease, Parvovirus B19, urologic and male genital diseases, lcsh:RC870-923, 0302 clinical medicine, Recurrence, hemic and lymphatic diseases, Escherichia coli Infections, Atypical Hemolytic Uremic Syndrome, Shiga-Toxigenic Escherichia coli, biology, Eculizumab, female genital diseases and pregnancy complications, Diarrhea, STEC, Nephrology, Complement Factor H, Vomiting, medicine.symptom, medicine.drug, Adult, Heterozygote, medicine.medical_specialty, Erythema Infectiosum, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, aHUS, Internal medicine, Case report, Complement C3b Inactivator Proteins, medicine, Genetic predisposition, Humans, HUS, Genetic Testing, Pathological, Parvovirus, business.industry, biology.organism_classification, lcsh:Diseases of the genitourinary system. Urology, 030104 developmental biology, Hemolytic-Uremic Syndrome, Immunology, Etiology, business
Abstract

Background Medical investigation is a favorite application of Ockham’s razor, in virtue of which when presented with competing hypotheses, the solution with the fewest assumptions should be privileged. Hemolytic uremic syndrome (HUS) encompasses diseases with distinct pathological mechanisms, such as HUS due to shiga-like toxin-producing bacteria (STEC-HUS) and atypical HUS, linked to defects in the alternate complement pathway. Other etiologies such as Parvovirus B19 infection are exceptional. All these causes are rare to such extent that we usually consider them mutually exclusive. We report here two cases of HUS that could be traced to multiple causes. Cases presentation Case 1 presented as vomiting and diarrhea. All biological characteristics of HUS were present. STEC was found in stool (by PCR and culture). After initial remission, a recurrence occurred and patient was started on Eculizumab. Genetic analysis revealed the heterozygous presence of a CFHR1/CFH hybrid gene. The issue was favorable under treatment. In case 2, HUS presented as fever, vomiting and purpura of the lower limbs. Skin lesions and erythroblastopenia led to suspect Parvovirus B19 primo-infection, which was confirmed by peripheral blood and medullar PCR. Concurrently, stool culture and PCR revealed the presence of STEC. Evolution showed spontaneous recovery. Conclusions Both cases defy Ockham’s razor in the sense that multiple causes could be traced to a single outcome; furthermore, they invite us to reflect on the physiopathology of HUS as they question the classical distinction between STEC-HUS and atypical HUS. We propose a two-hit mechanism model leading to HUS. Indeed, in case 1, HUS unfolded as a result of the synergistic interaction between an infectious trigger and a genetic predisposition. In case 2 however, it is the simultaneous occurrence of two infectious triggers that led to HUS. In dissent from Ockham’s razor, an exceptional disease such as HUS may stem from the sequential occurrence or co-occurrence of several rare conditions.

Published
2020
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42. A genome-wide association study identifies key modulators of complement factor H binding to malondialdehyde-epitopes

Author

Christoph J. Binder, Maria Ozsvar-Kozma, Nikolina Papac-Milicevic, Elisabeth B. Binder, Gregor Hoermann, Darina Czamara, Christine Skerka, Lejla Alic, Stefanie Haslinger-Hutter, Andrea Hartmann, Ramona B. Rudnick, Michael Gurbisz, and Peter F. Zipfel

Subjects
0301 basic medicine, malondialdehyde, Male, Genome-wide association study, Polymorphism, Single Nucleotide, Epitope, 03 medical and health sciences, Epitopes, Macular Degeneration, 0302 clinical medicine, Immunology and Inflammation, complement factor H-related protein 3, complement factor H-related protein 1, Complement C3b Inactivator Proteins, Humans, Genetic Predisposition to Disease, Tissue homeostasis, Aged, Genetics, Multidisciplinary, genome-wide association study, biology, Chemistry, Alternative splicing, complement factor H, Blood Proteins, Biological Sciences, Middle Aged, eye diseases, Complement system, 030104 developmental biology, 030220 oncology & carcinogenesis, Factor H, biology.protein, Alternative complement pathway, Female, sense organs, Antibody, Protein Binding
Abstract

Significance Dysregulation of the alternative complement pathway due to impaired binding of complement factor H (CFH) to self-ligands or altered self-ligands (e.g. malondialdehyde [MDA]-modified molecules) involved in homeostasis can promote the development of complement-related diseases, such as age-related macular degeneration (AMD). We identified, in an unbiased GWAS approach, that common genetic variants within the CFH gene family (rs1061170 and the deletion of the complement factor H-related protein 1 and 3 genes [CFHR3 and CFHR1]) act as major modulators of CFH recruitment and its ability to regulate complement on MDA-epitopes. These findings demonstrate the importance of the genetic status within the CFH/CFHR3/CFHR1 locus in tissue homeostasis and provide a mechanistic explanation as to why deletion of CFHR3/CFHR1 is protective in AMD development., Genetic variants within complement factor H (CFH), a major alternative complement pathway regulator, are associated with the development of age-related macular degeneration (AMD) and other complementopathies. This is explained with the reduced binding of CFH or its splice variant factor H-like protein 1 (FHL-1) to self-ligands or altered self-ligands (e.g., malondialdehyde [MDA]-modified molecules) involved in homeostasis, thereby causing impaired complement regulation. Considering the critical role of CFH in inhibiting alternative pathway activation on MDA-modified surfaces, we performed an unbiased genome-wide search for genetic variants that modify the ability of plasma CFH to bind MDA in 1,830 individuals and characterized the mechanistic basis and the functional consequences of this. In a cohort of healthy individuals, we identified rs1061170 in CFH and the deletion of CFHR3 and CFHR1 as dominant genetic variants that modify CFH/FHL-1 binding to MDA. We further demonstrated that FHR1 and FHR3 compete with CFH for binding to MDA-epitopes and that FHR1 displays the highest affinity toward MDA-epitopes compared to CFH and FHR3. Moreover, FHR1 bound to MDA-rich areas on necrotic cells and prevented CFH from mediating its cofactor activity on MDA-modified surfaces, resulting in enhanced complement activation. These findings provide a mechanistic explanation as to why the deletion of CFHR3 and CFHR1 is protective in AMD and highlight the importance of genetic variants within the CFH/CFHR3/CFHR1 locus in the recognition of altered-self in tissue homeostasis.

Published
2020

43. Researchers from Yale University Describe Findings in Vasculitis (Pearls & Oy-sters: Homozygous Complement Factor I Deficiency Presenting As Fulminant Relapsing Complement-mediated Cns Vasculitis).

Subjects
COMPLEMENT (Immunology), VASCULITIS, PROTEOLYTIC enzymes, BLOOD proteins, COMPLEMENT inhibition, BEHCET'S disease
Abstract

Keywords for this news article include: New Haven, Connecticut, United States, North and Central America, Blood Proteins, Cardiovascular Diseases and Conditions, Complement C3b Inactivator Proteins, Complement Factor I, Complement System Proteins, Enzymes and Coenzymes, Genetics, Health and Medicine, Immunology, Immunoproteins, Peptide Hydrolases, Serine Endopeptidases, Vasculitis, Yale University. Keywords: New Haven; State:Connecticut; United States; North and Central America; Blood Proteins; Cardiovascular Diseases and Conditions; Complement C3b Inactivator Proteins; Complement Factor I; Complement System Proteins; Enzymes and Coenzymes; Genetics; Health and Medicine; Immunology; Immunoproteins; Peptide Hydrolases; Serine Endopeptidases; Vasculitis EN New Haven State:Connecticut United States North and Central America Blood Proteins Cardiovascular Diseases and Conditions Complement C3b Inactivator Proteins Complement Factor I Complement System Proteins Enzymes and Coenzymes Genetics Health and Medicine Immunology Immunoproteins Peptide Hydrolases Serine Endopeptidases Vasculitis 828 828 1 08/28/23 20230828 NES 230828 2023 AUG 28 (NewsRx) -- By a News Reporter-Staff News Editor at Cardiovascular Week -- Investigators discuss new findings in Cardiovascular Diseases and Conditions - Vasculitis. [Extracted from the article]

Published
2023

44. Shanghai Jiao Tong University School of Medicine Researchers Have Published New Data on Schizophrenia (Effects of olanzapine on anhedonia in schizophrenia: mediated by complement factor H).

Subjects
COMPLEMENT factor H, ANHEDONIA, COMPLEMENT (Immunology), OLANZAPINE, SCHIZOPHRENIA
Abstract

According to the news reporters, the research concluded: "Our results implied that plasma CFH levels may be a biomarker for anhedonia in schizophrenia, and the effect of olanzapine on treating anhedonia is through decreasing plasma CFH levels." Keywords: Beta-Globulins; Biomarkers; Blood Proteins; Complement C3b Inactivator Proteins; Complement Factor H; Complement System Proteins; Diagnostics and Screening; Health and Medicine; Immunology; Immunoproteins; Mental Health Diseases and Conditions; Proteins; Psychiatry; Risk and Prevention; Schizophrenia EN Beta-Globulins Biomarkers Blood Proteins Complement C3b Inactivator Proteins Complement Factor H Complement System Proteins Diagnostics and Screening Health and Medicine Immunology Immunoproteins Mental Health Diseases and Conditions Proteins Psychiatry Risk and Prevention Schizophrenia 523 523 1 07/31/23 20230804 NES 230804 2023 JUL 31 (NewsRx) -- By a News Reporter-Staff News Editor at Mental Health Weekly Digest -- Researchers detail new data in schizophrenia. [Extracted from the article]

Published
2023

45. Studies from Singapore National Eye Centre Further Understanding of Complement C3b Inactivator Proteins (Genetic Variability of Complement Factor H Has Ethnicity-specific Associations With Choroidal Thickness).

Abstract

Keywords: Singapore; Asia; Beta-Globulins; Blood Proteins; Complement C3b Inactivator Proteins; Complement Factor H; Complement System Proteins; Genetics; Immunology; Immunoproteins; Proteins EN Singapore Asia Beta-Globulins Blood Proteins Complement C3b Inactivator Proteins Complement Factor H Complement System Proteins Genetics Immunology Immunoproteins Proteins 1524 1524 1 07/31/23 20230731 NES 230731 2023 AUG 4 (NewsRx) -- By a News Reporter-Staff News Editor at Genomics & Genetics Weekly -- Current study results on Proteins - Complement C3b Inactivator Proteins have been published. Singapore, Asia, Beta-Globulins, Blood Proteins, Complement C3b Inactivator Proteins, Complement System Proteins, Complement Factor H, Genetics, Immunology, Immunoproteins, Proteins. [Extracted from the article]

Published
2023

46. Researchers Submit Patent Application, "Methods Of Producing Recombinant Complement Proteins, Vectors And Therapeutic Uses Thereof", for Approval (USPTO 20230212635).

Abstract

"In certain embodiments, the nucleic acid molecule encoding the internal ribosome entry site is positioned between the nucleic acid molecule encoding the precursor Complement Factor I protein or variant thereof and the nucleic acid molecule encoding the furin protein. In certain embodiments, the nucleic acid molecule encoding precursor Complement Factor I is downstream of the nucleic acid molecule encoding furin protein, wherein the nucleic acid molecule encoding the self-cleaving peptide is positioned between the nucleic acid molecules encoding precursor Complement Factor I and furin protein. "In certain embodiments, the promoter element is upstream of the nucleic acid molecule encoding a precursor complement Factor I protein or variant thereof and nucleic acid molecule encoding a furin protein or variant thereof. "Preferably the nucleic acid molecule encoding the self-cleaving peptide is positioned between the nucleic acid molecule encoding the furin protein and the nucleic acid molecule encoding the precursor Complement Factor I protein. [Extracted from the article]

Published
2023

47. New Findings on Lung Cancer from Duke University Summarized (Antitumor Immune Mechanisms of the Anti-complement Factor H Gt103).

Abstract

Keywords: Durham; State:North Carolina; United States; North and Central America; Antibodies; Beta-Globulins; Blood Proteins; Cancer; Complement C3b Inactivator Proteins; Complement Factor H; Complement System Proteins; Drugs and Therapies; Health and Medicine; Immunoglobulins; Immunology; Immunoproteins; Lung Cancer; Lung Diseases and Conditions; Lung Neoplasms; Oncology; Pharmaceuticals; Proteins EN Durham State:North Carolina United States North and Central America Antibodies Beta-Globulins Blood Proteins Cancer Complement C3b Inactivator Proteins Complement Factor H Complement System Proteins Drugs and Therapies Health and Medicine Immunoglobulins Immunology Immunoproteins Lung Cancer Lung Diseases and Conditions Lung Neoplasms Oncology Pharmaceuticals Proteins 510 510 1 07/10/23 20230711 NES 230711 2023 JUL 11 (NewsRx) -- By a News Reporter-Staff News Editor at Cancer Weekly -- Data detailed on Oncology - Lung Cancer have been presented. GT103 causes complement C3 split product deposition on tumor cells in vitro and in vivo, triggers antibody-dependent cellular phagocytosis, and increases translocation of the danger-associated molecular pattern molecule calreticulin to the plasma membrane. The news correspondents obtained a quote from the research from Duke University, "The human mAb GT103, produced from a single CFH autoantibody-expressing B cell of a patient with lung cancer, recognizes a conformationally distinct epitope on tumor cells, kills tumor cells, and inhibits tumor growth in animal studies. [Extracted from the article]

Published
2023

48. Data on Preeclampsia Discussed by Researchers at University of Helsinki (Identification of Complement Factor H Variants That Predispose To Pre-eclampsia: a Genetic and Functional Study).

Abstract

Keywords for this news article include: Helsinki, Finland, Europe, Beta-Globulins, Blood Proteins, Complement C3b Inactivator Proteins, Complement Factor H, Complement System Proteins, Eclampsia, Genetics, Health and Medicine, Immunology, Immunoproteins, Obstetrics, Preeclampsia, Pregnancy Complications, Pregnancy-Induced Hypertension, Proteins, Women's Health, University of Helsinki. Keywords: Helsinki; Finland; Europe; Beta-Globulins; Blood Proteins; Complement C3b Inactivator Proteins; Complement Factor H; Complement System Proteins; Eclampsia; Genetics; Health and Medicine; Immunology; Immunoproteins; Obstetrics; Preeclampsia; Pregnancy Complications; Pregnancy-Induced Hypertension; Proteins; Women's Health EN Helsinki Finland Europe Beta-Globulins Blood Proteins Complement C3b Inactivator Proteins Complement Factor H Complement System Proteins Eclampsia Genetics Health and Medicine Immunology Immunoproteins Obstetrics Preeclampsia Pregnancy Complications Pregnancy-Induced Hypertension Proteins Women's Health 88 88 1 06/19/23 20230620 NES 230620 2023 JUN 22 (NewsRx) -- By a News Reporter-Staff News Editor at Women's Health Weekly -- Investigators discuss new findings in Pregnancy Complications - Preeclampsia. [Extracted from the article]

Published
2023

49. Duke University Researcher Adds New Data to Research in Non-Small Cell Lung Cancer [Results from a first-in-human phase 1B study of a complement factor H inhibitor (GT103) in patients with non-small cell lung cancer (NSCLC)].

Subjects
COMPLEMENT factor H, NON-small-cell lung carcinoma, COMPLEMENT (Immunology), ECULIZUMAB
Abstract

Keywords: Beta-Globulins; Blood Proteins; Cancer; Clinical Research; Clinical Trials and Studies; Complement C3b Inactivator Proteins; Complement Factor H; Complement System Proteins; Health and Medicine; Immunology; Immunoproteins; Lung Cancer; Lung Diseases and Conditions; Lung Neoplasms; Non-Small Cell Lung Cancer; Oncology; Proteins EN Beta-Globulins Blood Proteins Cancer Clinical Research Clinical Trials and Studies Complement C3b Inactivator Proteins Complement Factor H Complement System Proteins Health and Medicine Immunology Immunoproteins Lung Cancer Lung Diseases and Conditions Lung Neoplasms Non-Small Cell Lung Cancer Oncology Proteins 260 260 1 06/19/23 20230620 NES 230620 2023 JUN 20 (NewsRx) -- By a News Reporter-Staff News Editor at Clinical Oncology Week -- A new study on non-small cell lung cancer is now available. The news correspondents obtained a quote from the research from Duke University: "Monoclonal antibody inhibition of CFH facilitates complement-dependent tumor cell lysis, modulates the adaptive immune response, and inhibits tumor growth. [Extracted from the article]

Published
2023

50. Findings in Alzheimer Disease Reported from University of Helsinki (Reduced Binding of Apoe4 To Complement Factor H Promotes Amyloid-beta Oligomerization and Neuroinflammation).

Abstract

Keywords: Helsinki; Finland; Europe; Alzheimer Disease; Amyloid; Beta-Globulins; Blood Proteins; Complement C3b Inactivator Proteins; Complement Factor H; Complement System Proteins; Health and Medicine; Immunology; Immunoproteins; Neurodegenerative Diseases and Conditions; Neuroinflammation; Peptides and Proteins; Proteins; Risk and Prevention EN Helsinki Finland Europe Alzheimer Disease Amyloid Beta-Globulins Blood Proteins Complement C3b Inactivator Proteins Complement Factor H Complement System Proteins Health and Medicine Immunology Immunoproteins Neurodegenerative Diseases and Conditions Neuroinflammation Peptides and Proteins Proteins Risk and Prevention 571 571 1 06/12/23 20230616 NES 230616 2023 JUN 16 (NewsRx) -- By a News Reporter-Staff News Editor at Genomics & Genetics Weekly -- Research findings on Neurodegenerative Diseases and Conditions - Alzheimer Disease are discussed in a new report. Keywords for this news article include: Helsinki, Finland, Europe, Alzheimer Disease, Amyloid, Beta-Globulins, Blood Proteins, Complement C3b Inactivator Proteins, Complement Factor H, Complement System Proteins, Health and Medicine, Immunology, Immunoproteins, Neurodegenerative Diseases and Conditions, Neuroinflammation, Peptides and Proteins, Proteins, Risk and Prevention, University of Helsinki. [Extracted from the article]

Published
2023

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