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

• Published in: BMC immunology 2010-08, Vol.11 (1), p.43-43, Article 43
• Main Authors: Martini, Paolo G V, Cook, Lynette C, Alderucci, Scott, Norton, Angela W, Lundberg, Dianna M, Fish, Susan M, Langsetmo, Knut, Jönsson, Göran, Lood, Christian, Gullstrand, Birgitta, Zaleski, Kate J, Savioli, Nancy, Lottherand, Jason, Bedard, Charles, Gill, John, Concino, Michael F, Heartlein, Michael W, Truedsson, Lennart, Powell, Jan L, Tzianabos, Arthur O
• Format: Article
• Language: English
• Subjects: Adult; Autoimmune diseases; Bacteria; Bacterial infections; Basic Medicine; Care and treatment; Cell Line, Transformed; Child; Complement (Immunology); Complement C1 - immunology; Complement C1 - metabolism; Complement C2 - genetics; Complement C2 - metabolism; Complement C2 - therapeutic use; Complement C3 - immunology; Complement C3 - metabolism; Complement deficiency (Immunology); Complement Pathway, Classical - drug effects; Development and progression; Disease; Genetic aspects; Humans; Immune response; Immunologi inom det medicinska området; Immunologic Deficiency Syndromes - complications; Immunologic Deficiency Syndromes - drug therapy; Immunologic Deficiency Syndromes - genetics; Immunology in the medical area; Lupus; Lupus Erythematosus, Systemic - complications; Lupus Erythematosus, Systemic - drug therapy; Lupus Erythematosus, Systemic - genetics; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Physiological aspects; Protein Binding - drug effects; Proteins; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Recombinant Proteins - therapeutic use; Recurrence; Streptococcal Infections - complications; Streptococcal Infections - drug therapy; Streptococcal Infections - genetics; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - immunology
• ISSN: 1471-2172; 1471-2172
• DOI: 10.1186/1471-2172-11-43

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. 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. 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.