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.
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.
Martini
Paolo G V
PG
Department of Protein Expression and Purification Research, Shire Human Genetic Therapies Inc, 700 Main Street, Cambridge, MA 02139, USA. pmartini@shire.com
Cook
Lynette C
LC
Alderucci
Scott
S
Norton
Angela W
AW
Lundberg
Dianna M
DM
Fish
Susan M
SM
Langsetmo
Knut
K
Jönsson
Göran
G
Lood
Christian
C
Gullstrand
Birgitta
B
Zaleski
Kate J
KJ
Savioli
Nancy
N
Lottherand
Jason
J
Bedard
Charles
C
Gill
John
J
Concino
Michael F
MF
Heartlein
Michael W
MW
Truedsson
Lennart
L
Powell
Jan L
JL
Tzianabos
Arthur O
AO
D000328:Adult; D002461:Cell Line, Transformed; D002648:Child; D003172:Complement C1 / Q000276:immunology / Q000378:metabolism; D003175:Complement C2 / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000187:drug effects; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D011485:Protein Binding / Q000187:drug effects; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D012008:Recurrence; D013290:Streptococcal Infections / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D013296:Streptococcus pneumoniae / Q000276:immunology*
D003172:Complement C1; D003175:Complement C2; D003176:Complement C3; D011994:Recombinant Proteins