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Expression of properdin in complete and incomplete deficiency: normal in vitro synthesis by monocytes in two cases with properdin deficiency type II due to distinct mutations

Nordin Fredrikson, Gunilla LU ; Gullstrand, Birgitta LU ; Westberg, J; Sjöholm, Anders LU ; Uhlen, M and Truedsson, Lennart LU (1998) In Journal of Clinical Immunology 18(4). p.272-282
Abstract
Three properdin deficiency phenotypes have been reported--complete deficiency (type I), incomplete deficiency (type II), and dysfunction of properdin protein (type III)--all associated with increased susceptibility to meningococcal disease. Expression of properdin by monocytes was examined in type I deficiency and in two unrelated cases with type II deficiency, one from a Swedish and one from a Danish family. The properdin gene in the Danish family contained a point mutation in exon 8 causing a Gln316-->Arg substitution, distinct from a point mutation in exon 4 previously found in the Swedish family. Both genes coded for physicochemically abnormal properdin molecules with changed hydrophilicity. Monocytes from all the... (More)
Three properdin deficiency phenotypes have been reported--complete deficiency (type I), incomplete deficiency (type II), and dysfunction of properdin protein (type III)--all associated with increased susceptibility to meningococcal disease. Expression of properdin by monocytes was examined in type I deficiency and in two unrelated cases with type II deficiency, one from a Swedish and one from a Danish family. The properdin gene in the Danish family contained a point mutation in exon 8 causing a Gln316-->Arg substitution, distinct from a point mutation in exon 4 previously found in the Swedish family. Both genes coded for physicochemically abnormal properdin molecules with changed hydrophilicity. Monocytes from all the properdin-deficient individuals produced properdin mRNA in a normal fashion. In type I deficiency no intracellular or secreted properdin was found, indicating rapid intracellular degradation. Monocytes from the males with type II deficiency expressed and secreted properdin normally. Properdin in sera with type II deficiency showed abnormal oligomerization with a relative decrease in properdin trimers and tetramers. Our findings suggest that the low concentration of circulating properdin in type II deficiency is caused by increased extracellular catabolism. Analysis of properdin expression by monocytes in a female carrier in the family with properdin deficiency type I provided direct evidence of lyonization at the cellular level. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Complement, human, lyonization, oligomerization, X chromosome
in
Journal of Clinical Immunology
volume
18
issue
4
pages
272 - 282
publisher
Springer
external identifiers
  • pmid:9710744
  • scopus:0031829197
ISSN
0271-9142
DOI
10.1023/A:1027385806871
language
English
LU publication?
yes
id
fd6fd1ac-a325-41c1-90af-4c2e6e6b0b98 (old id 1113304)
date added to LUP
2008-07-14 16:15:30
date last changed
2017-07-23 04:45:49
@article{fd6fd1ac-a325-41c1-90af-4c2e6e6b0b98,
  abstract     = {Three properdin deficiency phenotypes have been reported--complete deficiency (type I), incomplete deficiency (type II), and dysfunction of properdin protein (type III)--all associated with increased susceptibility to meningococcal disease. Expression of properdin by monocytes was examined in type I deficiency and in two unrelated cases with type II deficiency, one from a Swedish and one from a Danish family. The properdin gene in the Danish family contained a point mutation in exon 8 causing a Gln316-->Arg substitution, distinct from a point mutation in exon 4 previously found in the Swedish family. Both genes coded for physicochemically abnormal properdin molecules with changed hydrophilicity. Monocytes from all the properdin-deficient individuals produced properdin mRNA in a normal fashion. In type I deficiency no intracellular or secreted properdin was found, indicating rapid intracellular degradation. Monocytes from the males with type II deficiency expressed and secreted properdin normally. Properdin in sera with type II deficiency showed abnormal oligomerization with a relative decrease in properdin trimers and tetramers. Our findings suggest that the low concentration of circulating properdin in type II deficiency is caused by increased extracellular catabolism. Analysis of properdin expression by monocytes in a female carrier in the family with properdin deficiency type I provided direct evidence of lyonization at the cellular level.},
  author       = {Nordin Fredrikson, Gunilla and Gullstrand, Birgitta and Westberg, J and Sjöholm, Anders and Uhlen, M and Truedsson, Lennart},
  issn         = {0271-9142},
  keyword      = {Complement,human,lyonization,oligomerization,X chromosome},
  language     = {eng},
  number       = {4},
  pages        = {272--282},
  publisher    = {Springer},
  series       = {Journal of Clinical Immunology},
  title        = {Expression of properdin in complete and incomplete deficiency: normal in vitro synthesis by monocytes in two cases with properdin deficiency type II due to distinct mutations},
  url          = {http://dx.doi.org/10.1023/A:1027385806871},
  volume       = {18},
  year         = {1998},
}