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Recombinant human complement component C2 produced in a human cell line restores the classical complement pathway activity in-vitro: an alternative treatment for C2 deficiency diseases

Martini, Paolo G. V.; Cook, Lynette C.; Alderucci, Scott; Norton, Angela W.; Lundberg, Dianna M.; Fish, Susan M.; Langsetmo, Knut; Jönsson, Göran LU ; Lood, Christian LU and Gullstrand, Birgitta LU , et al. (2010) In BMC Immunology 11.
Abstract
Background: Complement C2 deficiency is the most common genetically determined complete complement deficiency and is associated with a number of diseases. Most prominent are the associations with recurrent serious infections in young children and the development of systemic lupus erythematosus (SLE) in adults. The links with these diseases reflect the important role complement C2 plays in both innate immunity and immune tolerance. Infusions with normal fresh frozen plasma for the treatment of associated disease have demonstrated therapeutic effects but so far protein replacement therapy has not been evaluated. Results: Human complement C2 was cloned and expressed in a mammalian cell line. The purity of recombinant human C2 (rhC2) was... (More)
Background: Complement C2 deficiency is the most common genetically determined complete complement deficiency and is associated with a number of diseases. Most prominent are the associations with recurrent serious infections in young children and the development of systemic lupus erythematosus (SLE) in adults. The links with these diseases reflect the important role complement C2 plays in both innate immunity and immune tolerance. Infusions with normal fresh frozen plasma for the treatment of associated disease have demonstrated therapeutic effects but so far protein replacement therapy has not been evaluated. Results: Human complement C2 was cloned and expressed in a mammalian cell line. The purity of recombinant human C2 (rhC2) was greater than 95% and it was characterized for stability and activity. It was sensitive to C1s cleavage and restored classical complement pathway activity in C2-deficient serum both in a complement activation ELISA and a hemolytic assay. Furthermore, rhC2 could increase C3 fragment deposition on the human pathogen Streptococcus pneumoniae in C2-deficient serum to levels equal to those with normal serum. Conclusions: Taken together these data suggest that recombinant human C2 can restore classical complement pathway activity and may serve as a potential therapeutic for recurring bacterial infections or SLE in C2-deficient patients. (Less)
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published
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BMC Immunology
volume
11
publisher
BioMed Central
external identifiers
  • wos:000283128400001
  • scopus:77955677450
ISSN
1471-2172
DOI
10.1186/1471-2172-11-43
language
English
LU publication?
yes
id
4be81c8b-fba3-4cb1-88ef-7fd8d2389207 (old id 1721088)
date added to LUP
2010-12-03 12:36:20
date last changed
2018-05-29 09:20:10
@article{4be81c8b-fba3-4cb1-88ef-7fd8d2389207,
  abstract     = {Background: Complement C2 deficiency is the most common genetically determined complete complement deficiency and is associated with a number of diseases. Most prominent are the associations with recurrent serious infections in young children and the development of systemic lupus erythematosus (SLE) in adults. The links with these diseases reflect the important role complement C2 plays in both innate immunity and immune tolerance. Infusions with normal fresh frozen plasma for the treatment of associated disease have demonstrated therapeutic effects but so far protein replacement therapy has not been evaluated. Results: Human complement C2 was cloned and expressed in a mammalian cell line. The purity of recombinant human C2 (rhC2) was greater than 95% and it was characterized for stability and activity. It was sensitive to C1s cleavage and restored classical complement pathway activity in C2-deficient serum both in a complement activation ELISA and a hemolytic assay. Furthermore, rhC2 could increase C3 fragment deposition on the human pathogen Streptococcus pneumoniae in C2-deficient serum to levels equal to those with normal serum. Conclusions: Taken together these data suggest that recombinant human C2 can restore classical complement pathway activity and may serve as a potential therapeutic for recurring bacterial infections or SLE in C2-deficient patients.},
  author       = {Martini, Paolo G. V. and Cook, Lynette C. and Alderucci, Scott and Norton, Angela W. and Lundberg, Dianna M. and Fish, Susan M. and Langsetmo, Knut and Jönsson, Göran and Lood, Christian and Gullstrand, Birgitta and Zaleski, Kate J. and Savioli, Nancy and Lottherand, Jason and Bedard, Charles and Gill, John and Concino, Michael F. and Heartlein, Michael W. and Truedsson, Lennart and Powell, Jan L. and Tzianabos, Arthur O.},
  issn         = {1471-2172},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {BMC Immunology},
  title        = {Recombinant human complement component C2 produced in a human cell line restores the classical complement pathway activity in-vitro: an alternative treatment for C2 deficiency diseases},
  url          = {http://dx.doi.org/10.1186/1471-2172-11-43},
  volume       = {11},
  year         = {2010},
}