Anti-mouse properdin TSR 5/6 monoclonal antibodies block complement alternative pathway-dependent pathogenesis.

In this report we use a portion of the mouse properdin protein, expressed in a bacterial system, to raise rabbit polyclonal and hamster monoclonal antibodies that block properdin-dependent pathogenesis. These antibodies, when employed with AP-dependent mouse disease models, can help evaluate the feasibility of properdin-directed therapy. PMID: 25723276 [PubMed - indexed for MEDLINE]
Source: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy - Category: Microbiology Tags: Monoclon Antib Immunodiagn Immunother Source Type: research

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Publication date: October 2019Source: Molecular Immunology, Volume 114Author(s): Jutta Schröder-Braunstein, Michael KirschfinkAbstractComplement defects are associated with an enhanced risk of a broad spectrum of infectious as well as systemic or local inflammatory and thrombotic disorders. Inherited complement deficiencies have been described for virtually all complement components but can be mimicked by autoantibodies, interfering with the activity of specific complement components, convertases or regulators. While being rare, diseases related to complement deficiencies are often severe with a frequent but not exclu...
Source: Molecular Immunology - Category: Allergy & Immunology Source Type: research
In conclusion, we have confirmed in our cohort of patients, the strong association between FHR1 deficiency and aHUS with anti-FH autoantibodies. Through an innovative approach based on the comparison with “supercontrols” carrying the homozygous CFHR1 deletion, identified by screening a large number of healthy adult subjects, we have documented that patients with anti-FHs aHUS are enriched in complement gene LPVs. This observation indicates that the pathogenesis of anti-FHs aHUS is complex and multiple “hits” are required for its clinical manifestation. We also document that the CFH H3 and the CD46GG...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Abstract Single nucleotide polymorphisms and rare mutations in Factor H (FH; official name CFH) are associated with age-related macular degeneration and atypical hemolytic uremic syndrome, a form of thrombotic microangiopathy. Mice with the FH W1206R mutation (FHR/R) share features with human atypical hemolytic uremic syndrome. Here, we report that FHR/R mice exhibited retinal vascular occlusion and ischemia. Retinal fluorescein angiography demonstrated delayed perfusion and vascular leakage in FHR/R mice. Optical coherence tomography imaging of FHR/R mice showed retinal degeneration, edema, and detachment. Histol...
Source: Am J Pathol - Category: Pathology Authors: Tags: Am J Pathol Source Type: research
Single nucleotide polymorphisms and rare mutations in Factor H (FH; official name CFH) are associated with age-related macular degeneration and atypical hemolytic uremic syndrome, a form of thrombotic microangiopathy. Mice with the FH W1206R mutation (FHR/R) share features with human atypical hemolytic uremic syndrome. Here, we report that FHR/R mice exhibited retinal vascular occlusion and ischemia. Retinal fluorescein angiography demonstrated delayed perfusion and vascular leakage in FHR/R mice.
Source: American Journal of Pathology - Category: Pathology Authors: Tags: Regular article Source Type: research
In conclusion, we observed a substantial overlap of variants between aHUS/C3G and AMD, however, there is a distinct clustering of variants within specific domains. This article is protected by copyright. All rights reserved. PMID: 29888403 [PubMed - as supplied by publisher]
Source: Clinical Genetics - Category: Genetics & Stem Cells Authors: Tags: Clin Genet Source Type: research
Structural variation and single-nucleotide variation of the complement factor H (CFH) gene family underlie several complex genetic diseases, including age-related macular degeneration (AMD) and atypical hemolytic uremic syndrome (AHUS). To understand its diversity and evolution, we performed high-quality sequencing of this ∼360-kbp locus in six primate lineages, including multiple human...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: PNAS Plus Source Type: research
Spontaneous activation enables the complement system to respond very rapidly to diverse threats. This activation is efficiently suppressed by complement factor H (CFH) on self-surfaces but not on foreign surfaces. The surface selectivity of CFH, a soluble protein containing 20 complement-control protein modules (CCPs 1–20), may be compromised by disease-linked mutations. However, which of the several functions of CFH drives this self-surface selectivity remains unknown. To address this, we expressed human CFH mutants in Pichia pastoris. We found that recombinant I62-CFH (protective against age-related macular degener...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Immunology Source Type: research
Genetic defects in complement regulatory proteins can lead to severe renal diseases, including atypical hemolytic uremic syndrome and C3 glomerulopathies, and age-related macular degeneration. The majority of the mutations found in patients with these diseases affect the glycoprotein complement factor H, the main regulator of the alternative pathway of complement activation. Therapeutic options are limited, and novel treatments, specifically those targeting alternative pathway activation, are highly desirable. Substitution with biologically active factor H could potentially treat a variety of diseases that involve increase...
Source: Journal of the American Society of Nephrology : JASN - Category: Urology & Nephrology Authors: Tags: Basic Research Source Type: research
Publication date: Available online 16 February 2017 Source:Molecular Immunology Author(s): Janez Ferluga, Lubna Kouser, Valarmathy Murugaiah, Robert B. Sim, Uday Kishore Complement system homeostasis is important for host self-protection and anti-microbial immune surveillance, and recent research indicates roles in tissue development and remodelling. Complement also appears to have several points of interaction with the blood coagulation system. Deficiency and altered function due to gene mutations and polymorphisms in complement effectors and regulators, including Factor H, have been associated with familial and sporadic...
Source: Molecular Immunology - Category: Allergy & Immunology Source Type: research
Abstract Complement, a part of the humoral innate immune system, is divided into three pathways. The classical and mannose-binding lectin pathways are triggered by specific recognition of foreign targets. Conversely, the alternative pathway (AP) is actively down-regulated on host tissue. Glycosaminoglycans (GAGs) and sialylated glycans mediate host recognition of the AP as self-associated molecular patterns (SAMPs) to the regulatory protein factor H (FH). This review summarizes the more recent years of research on SAMP recognition by FH from a structural biology point of view and discusses implications for two com...
Source: Current Opinion in Structural Biology - Category: Biology Authors: Tags: Curr Opin Struct Biol Source Type: research
More News: Age-Related Macular Degeneration (AMD) | Hemolytic Uremic Syndrome (HUS) | Immunotherapy | Microbiology