Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease
Zöller, Bengt LU
; Garcia de Frutos, P.
LU
and Dahlbäck, Björn
LU
(1995)
In Blood
85(12).
p.3524-3531
- Abstract
- Type III protein S deficiency is characterized by a low plasma level of free protein S, whereas the total concentration of protein S is normal. In contrast, both free and total protein S levels are low in type I deficiency. To elucidate the molecular mechanism behind the selective deficiency of free protein S in type III deficiency, the relationship between the plasma concentrations of β-chain containing isoforms of C4b-binding protein (C4BPβ+) and different forms of protein S (free, bound, and total) was evaluated in 327 members of 18 protein S-deficient families. In normal relatives (n = 190), protein S correlated well with C4BPβ+ with free protein S (96 ± 23 nmol/L) being equal to the molar excess of protein S (355 ± 65 nmol/L) over... (More)
- Type III protein S deficiency is characterized by a low plasma level of free protein S, whereas the total concentration of protein S is normal. In contrast, both free and total protein S levels are low in type I deficiency. To elucidate the molecular mechanism behind the selective deficiency of free protein S in type III deficiency, the relationship between the plasma concentrations of β-chain containing isoforms of C4b-binding protein (C4BPβ+) and different forms of protein S (free, bound, and total) was evaluated in 327 members of 18 protein S-deficient families. In normal relatives (n = 190), protein S correlated well with C4BPβ+ with free protein S (96 ± 23 nmol/L) being equal to the molar excess of protein S (355 ± 65 nmol/L) over C4BPβ+ (275 ± 47 nmol/L). In protein S-deficient family members (n = 117), the equimolar relationship between protein S (215 ± 50 nmol/L) and C4BPβ+ (228 ± 51 nmol/L), together with the high affinity of the interaction, resulted in low levels of free protein S (16 ± 10 nmol/L). Free protein S levels were distinctly low in proteinS-deficient members, whereas in 47 of the protein S-deficient individuals, the concentration of total protein S was within the normal range, which fulfills the criteria for type III deficiency. The remaining 70 had low levels of both total and free protein S and, accordingly, would be type I deficient. Coexistence of type I and type III deficiency was found in 14 families, suggesting the two types of protein S deficiency to be phenotypic variants of the same genetic disease. Interestingly, not only protein S but also C4BPβ+ levels were decreased in orally anticoagulated controls and even more so in anticoagulated protein S- deficient members, suggesting that the concentration of C4BPβ+ is influenced by that of protein S. In conclusion, our results indicate that type I and type III deficiencies are phenotypic variants of the same genetic disease and that the low plasma concentrations of free protein S in both types are the result of an equimolar relationship between protein S and C4BPβ+. (Less)
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https://lup.lub.lu.se/record/47893182-6508-49f9-a59c-431367abd97f
- author
- Zöller, Bengt
LU
; Garcia de Frutos, P.
LU
and Dahlbäck, Björn
LU
- organization
- publishing date
- 1995-11-02
- type
- Contribution to journal
- publication status
- published
- keywords
- CD4 antigen, protein S, warfarin, adolescent, adult, aged, anticoagulation, article, binding affinity, child, clinical article, controlled study, female, genetic risk, human, human cell, human tissue, male, phenotype, priority journal, protein binding, protein blood level, protein defect, protein deficiency, protein S deficiency
- in
- Blood
- volume
- 85
- issue
- 12
- pages
- 8 pages
- publisher
- American Society of Hematology
- external identifiers
-
- pmid:7780139
- scopus:0029017118
- ISSN
- 0006-4971
- language
- English
- LU publication?
- yes
- id
- 47893182-6508-49f9-a59c-431367abd97f
- date added to LUP
- 2017-10-19 16:29:10
- date last changed
- 2024-02-13 09:28:21
@article{47893182-6508-49f9-a59c-431367abd97f,
abstract = {{Type III protein S deficiency is characterized by a low plasma level of free protein S, whereas the total concentration of protein S is normal. In contrast, both free and total protein S levels are low in type I deficiency. To elucidate the molecular mechanism behind the selective deficiency of free protein S in type III deficiency, the relationship between the plasma concentrations of β-chain containing isoforms of C4b-binding protein (C4BPβ+) and different forms of protein S (free, bound, and total) was evaluated in 327 members of 18 protein S-deficient families. In normal relatives (n = 190), protein S correlated well with C4BPβ+ with free protein S (96 ± 23 nmol/L) being equal to the molar excess of protein S (355 ± 65 nmol/L) over C4BPβ+ (275 ± 47 nmol/L). In protein S-deficient family members (n = 117), the equimolar relationship between protein S (215 ± 50 nmol/L) and C4BPβ+ (228 ± 51 nmol/L), together with the high affinity of the interaction, resulted in low levels of free protein S (16 ± 10 nmol/L). Free protein S levels were distinctly low in proteinS-deficient members, whereas in 47 of the protein S-deficient individuals, the concentration of total protein S was within the normal range, which fulfills the criteria for type III deficiency. The remaining 70 had low levels of both total and free protein S and, accordingly, would be type I deficient. Coexistence of type I and type III deficiency was found in 14 families, suggesting the two types of protein S deficiency to be phenotypic variants of the same genetic disease. Interestingly, not only protein S but also C4BPβ+ levels were decreased in orally anticoagulated controls and even more so in anticoagulated protein S- deficient members, suggesting that the concentration of C4BPβ+ is influenced by that of protein S. In conclusion, our results indicate that type I and type III deficiencies are phenotypic variants of the same genetic disease and that the low plasma concentrations of free protein S in both types are the result of an equimolar relationship between protein S and C4BPβ+.}},
author = {{Zöller, Bengt and Garcia de Frutos, P. and Dahlbäck, Björn}},
issn = {{0006-4971}},
keywords = {{CD4 antigen; protein S; warfarin; adolescent; adult; aged; anticoagulation; article; binding affinity; child; clinical article; controlled study; female; genetic risk; human; human cell; human tissue; male; phenotype; priority journal; protein binding; protein blood level; protein defect; protein deficiency; protein S deficiency}},
language = {{eng}},
month = {{11}},
number = {{12}},
pages = {{3524--3531}},
publisher = {{American Society of Hematology}},
series = {{Blood}},
title = {{Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease}},
volume = {{85}},
year = {{1995}},
}