scholarly journals SP105ATYPICAL HEMOLYTIC UREMIC SYNDROME AND C3 GLOMERULOPATHY DUE TO MONOCLONAL ANTIBODY AGAINST COMPLEMENT CONTROL PROTEIN FACTOR H

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Paraskevi Eva Andronikidis ◽  
Papanikolaou Vasiliki ◽  
Plavoukou Styliani ◽  
Tsouka Glykeria ◽  
Delibasi Sosanna ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hemolytic Uremic Syndrome ◽  
Factor H ◽  
C3 Glomerulopathy ◽  
Complement Control Protein ◽  
Protein Factor ◽  
Uremic Syndrome ◽  
Control Protein

scholarly journals CFHR Gene Variations Provide Insights in the Pathogenesis of the Kidney Diseases Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy

2020 ◽  
Vol 31 (2) ◽  
pp. 241-256 ◽  
Author(s):  
Peter F. Zipfel ◽  
Thorsten Wiech ◽  
Emma D. Stea ◽  
Christine Skerka
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Kidney Diseases ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Human Kidney ◽  
Copy Number Variations ◽  
Factor H ◽  
C3 Glomerulopathy ◽  
Hybrid Proteins ◽  
Genetic Modifications ◽  
Uremic Syndrome

Sequence and copy number variations in the human CFHR–Factor H gene cluster comprising the complement genes CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, and Factor H are linked to the human kidney diseases atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy. Distinct genetic and chromosomal alterations, deletions, or duplications generate hybrid or mutant CFHR genes, as well as hybrid CFHR–Factor H genes, and alter the FHR and Factor H plasma repertoire. A clear association between the genetic modifications and the pathologic outcome is emerging: CFHR1, CFHR3, and Factor H gene alterations combined with intact CFHR2, CFHR4, and CFHR5 genes are reported in atypical hemolytic uremic syndrome. But alterations in each of the five CFHR genes in the context of an intact Factor H gene are described in C3 glomerulopathy. These genetic modifications influence complement function and the interplay of the five FHR proteins with each other and with Factor H. Understanding how mutant or hybrid FHR proteins, Factor H::FHR hybrid proteins, and altered Factor H, FHR plasma profiles cause pathology is of high interest for diagnosis and therapy.

Monoclonal antibodies against the complement control protein Factor H (β1 H)

1983 ◽  
Vol 3 (12) ◽  
pp. 1119-1131 ◽  
Author(s):  
E. Sim ◽  
M. S. Palmer ◽  
M. Puklavec ◽  
R. B. Sim
Keyword(s):  
Monoclonal Antibodies ◽  
Human Factor ◽  
Factor H ◽  
Single Chain ◽  
Chain Molecules ◽  
Complement Control Protein ◽  
Protein Factor ◽  
Green Monkey ◽  
Cofactor Activity ◽  
Control Protein

Two mouse monoclonal antibodies against the human complement control protein, Factor H (β1H), are described. The antibodies are both IgG − γ1 - subclasses and are directed against different epitopes on the human Factor H molecule. One of the antibodies, MRC OX 24, increases the cofactor activity of Factor H in Factor I-mediated cleavage of soluble C3b. The second antibody, MRC OX 23, which has no effect alone, reduces the increase in cofactor activity observed in the presence of the first antibody. However, MRC OX 24 inhibits the binding of 125I-labelled Factor H to surface-bound C3b (EAC3b). Again MRC OX 23 alone does not have any effect but decreases the inhibition in 125I-Labelled Factor H binding to EAC3b observed with MRC OX 24. These studies show clearly that the interaction of Factor H with soluble C3b is different to its interaction with surface-bound C3b. In an indirect immunoprecipitation system using these monoclonal antibodies, single-chain molecules of 150 000 mol. wt. are specifically precipitated from human serum and also from the sera of other primates - rhesus monkey, cynomolgus monkey, and African green monkey. There was no precipitation from sera of cow, pig, sheep, chick, or rabbit. Using a radioimmunoassay with radiolabelled monoclonal MRC OX 23, the concentration of Factor H in human plasma was determined.

scholarly journals C3 Glomerulopathy and Atypical Hemolytic Uremic Syndrome: Two Important Manifestations of Complement System Dysfunction

2018 ◽  
Vol 8 (1) ◽  
pp. 25-34 ◽  
Author(s):  
Ravneet Bajwa ◽  
John A. DePalma ◽  
Taimoor Khan ◽  
Anmol Cheema ◽  
Sheila A. Kalathil ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hemolytic Uremic Syndrome ◽  
Renal Dysfunction ◽  
Female Patient ◽  
Alternative Pathway ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Organ Injury ◽  
C3 Glomerulopathy ◽  
Kidney Involvement ◽  
Uremic Syndrome

The advances in our understanding of the alternative pathway have emphasized that uncontrolled hyperactivity of this pathway causes 2 distinct disorders that adversely impact the kidney. In the so-called atypical hemolytic uremic syndrome (aHUS), renal dysfunction occurs along with thrombocytopenia, anemia, and target organ injury to multiple organs, most commonly the kidney. On the other hand, in the so-termed C3 glomerulopathy, kidney involvement is not associated with thrombocytopenia, anemia, or other system involvement. In this report, we present 2 cases of alternative pathway dysfunction. The 60-year-old female patient had biopsy-proven C3 glomerulopathy, while the 32-year-old female patient was diagnosed with aHUS based on renal dysfunction, thrombocytopenia, anemia, and normal ADAMTS-13 level. The aHUS patient was successfully treated with the monoclonal antibody (eculizumab) for complement blockade. The patient with C3 glomerulopathy did not receive the monoclonal antibody. In this patient, management focused on blood pressure and proteinuria control with an angiotensin-converting enzyme inhibitor. This article focuses on the clinical differences, pathophysiology, and treatment of aHUS and C3 glomerulopathy.

scholarly journals Human complement factor H deficiency associated with hemolytic uremic syndrome.

1998 ◽  
Vol 9 (12) ◽  
pp. 2318-2326
Author(s):  
N Rougier ◽  
M D Kazatchkine ◽  
J P Rougier ◽  
V Fremeaux-Bacchi ◽  
J Blouin ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Regulatory Protein ◽  
Large Deletion ◽  
Factor H ◽  
Pcr Analysis ◽  
Complement Factor ◽  
Human Complement ◽  
Protein Factor ◽  
Factor H Deficiency ◽  
Uremic Syndrome

This study reports on six cases of deficiency in the human complement regulatory protein Factor H (FH) in the context of an acute renal disease. Five of the cases were observed in children presenting with idiopathic hemolytic uremic syndrome (HUS). Two of the children exhibited a homozygous deficiency characterized by the absence of the 150-kD form of Factor H and the presence, upon immunoblotting, of the 42-kD Factor H-like protein 1 (FHL-1) and other FH-related protein (FHR) bands. Southern blot and PCR analysis of DNA of one patient with homozygous deficiency ruled out the presence of a large deletion of the FH gene as the underlying defect for the deficiency. The other four children presented with heterozygous deficiency and exhibited a normal immunoblotting pattern of proteins of the FH family. Factor H deficiency is the only complement deficiency associated with HUS. These observations suggest a role for FH and/or FH receptors in the pathogenesis of idiopathic HUS.

scholarly journals Complement control protein factor H: The good, the bad, and the inadequate

2010 ◽  
Vol 47 (13) ◽  
pp. 2187-2197 ◽  
Author(s):  
Viviana P. Ferreira ◽  
Michael K. Pangburn ◽  
Claudio Cortés
Keyword(s):  
Factor H ◽  
Complement Control Protein ◽  
Protein Factor ◽  
Control Protein

scholarly journals Blocking Properdin Prevents Complement-Mediated Hemolytic Uremic Syndrome and Systemic Thrombophilia

2018 ◽  
Vol 29 (7) ◽  
pp. 1928-1937 ◽  
Author(s):  
Yoshiyasu Ueda ◽  
Takashi Miwa ◽  
Damodar Gullipalli ◽  
Sayaka Sato ◽  
Daisuke Ito ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Murine Model ◽  
Alternative Pathway ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Factor H ◽  
C3 Glomerulopathy ◽  
P Deficiency ◽  
Renal Histology ◽  
Uremic Syndrome ◽  
Alternative Pathway Of Complement

Background Properdin (P) is a positive regulator of the alternative pathway of complement activation. Although P inhibition is expected and has been shown to ameliorate the alternative pathway of complement-mediated tissue injury in several disease models, it unexpectedly exacerbated renal injury in a murine model of C3 glomerulopathy. The role of P in atypical hemolytic uremic syndrome (aHUS) is uncertain.Methods We blocked P function by genetic deletion or mAb-mediated inhibition in mice carrying a factor H (FH) point mutation, W1206R (FHR/R), that causes aHUS and systemic thrombophilia with high mortality.Results P deficiency completely rescued FHR/R mice from premature death and prevented thrombocytopenia, hemolytic anemia, and renal disease. It also eliminated macrovessel thrombi that were prevalent in FHR/R mice. All mice that received a function-blocking anti-P mAb for 8 weeks survived the experimental period and appeared grossly healthy. Platelet counts and hemoglobin levels were significantly improved in FHR/R mice after 4 weeks of anti-P mAb treatment. One half of the FHR/R mice treated with an isotype control mAb but none of the anti-P mAb-treated mice developed stroke-related neurologic disease. Anti-P mAb-treated FHR/R mice showed largely normal renal histology, and residual liver thrombi were detected in only three of 15 treated mice.Conclusions These results contrast with the detrimental effect of P inhibition observed in a murine model of C3 glomerulopathy and suggest that P contributes critically to aHUS pathogenesis. Inhibition of P in aHUS may be of therapeutic benefit.

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