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Further studies of the down-regulation by Factor I of the C3b feedback cycle using endotoxin as a soluble activator and red cells as a source of CR1 on sera of different complotype.
- Source :
-
Clinical and experimental immunology [Clin Exp Immunol] 2016 Jan; Vol. 183 (1), pp. 150-6. Date of Electronic Publication: 2015 Nov 05. - Publication Year :
- 2016
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Abstract
- In this paper we have extended our earlier studies of the action of increasing Factor I concentration on complement activation by using a soluble activator, lipopolysaccharide (LPS) endotoxin, and using human erythrocytes as a source of CR1 - the co-factor needed for the final clip of iC3b to C3dg by Factor I. Using this more physiological system, the results show that we can predict that a quite modest increase in Factor I concentration - 22 µg/ml of extra Factor I - will convert the activity of the highest risk sera to those of the lowest risk. Preliminary experiments have been performed with erythrocytes allotyped for CR1 number. While we have not been able to perform an adequate study of their co-factor activities in our assays, preliminary experiments suggest that when Factor I levels are increased the difference produced by different allotypes of red cells is largely overcome. This suggests that in patients with paroxysmal nocturnal haemoglobinuria (PNH) treated with eculizumab, additional treatment with Factor I may be very useful in reducing the need for blood transfusion. We have also explored the age-related allele frequency for the two polymorphisms of Factor H and the polymorphism of C3. In our population, unlike the 1975 study, we found no age variation in the allele frequency in these polymorphisms. This may, however, reflect that the Cambridge BioResource volunteers do not include many very young or very elderly patients, and in general comprise a population not greatly at risk of death from infectious disease.<br /> (© 2015 British Society for Immunology.)
- Subjects :
- Adolescent
Adult
Age Factors
Aged
Antibodies, Monoclonal, Humanized therapeutic use
Complement C3b genetics
Complement Factor I analysis
Down-Regulation
Gene Frequency
Hemoglobinuria, Paroxysmal therapy
Humans
Immune Sera metabolism
Lipopolysaccharides immunology
Middle Aged
Polymorphism, Genetic
Young Adult
Complement C3b metabolism
Complement Factor H genetics
Complement Factor I immunology
Erythrocytes immunology
Hemoglobinuria, Paroxysmal blood
Receptors, Complement 3b immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2249
- Volume :
- 183
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Clinical and experimental immunology
- Publication Type :
- Academic Journal
- Accession number :
- 26415566
- Full Text :
- https://doi.org/10.1111/cei.12714