Email updates

Keep up to date with the latest news and content from BMC Immunology and BioMed Central.

Open Access Highly Accessed Research article

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

Paolo GV Martini1*, Lynette C Cook1, Scott Alderucci1, Angela W Norton1, Dianna M Lundberg1, Susan M Fish1, Knut Langsetmo1, Göran Jönsson2, Christian Lood3, Birgitta Gullstrand3, Kate J Zaleski4, Nancy Savioli4, Jason Lottherand4, Charles Bedard5, John Gill5, Michael F Concino1, Michael W Heartlein6, Lennart Truedsson3, Jan L Powell4 and Arthur O Tzianabos6

Author Affiliations

1 Department of Protein Expression and Purification Research, Shire Human Genetic Therapies Inc., 700 Main Street, Cambridge, MA 02139, USA

2 Department of Infectious Diseases, Lund University Hospital, Klinikgatan 3, Lund 221 85, Sweden

3 Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology, Lund University, Solvegatan 23, Lund 223 62, Sweden

4 Department of Physiology, Shire Human Genetic Therapies Inc., 700 Main Street, Cambridge, MA 02139, USA

5 Department of Cell Culture Process Development, Shire Human Genetic Therapies Inc., 700 Main Street, Cambridge, MA 02139, USA

6 Department of Discovery, Shire Human Genetic Therapies Inc., 700 Main Street, Cambridge, MA 02139, USA

For all author emails, please log on.

BMC Immunology 2010, 11:43  doi:10.1186/1471-2172-11-43

Published: 20 August 2010

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.