TY - CHAP
T1 - Targeting classical complement pathway to treat complement mediated autoimmune diseases
AU - Tüzün, Erdem
AU - Li, Jing
AU - Saini, Shamsher S.
AU - Yang, Huan
AU - Christadoss, Premkumar
PY - 2008
Y1 - 2008
N2 - Mice deficient for classical complement pathway (CCP) factor C4 are resistant to antibody and complement mediated experimental autoimmune myasthenia gravis (EAMG). Anti-C1q antibody administration before or following acetylcholine receptor immunization suppresses EAMG development by reducing lymph node cell IL-6 production and neuromuscular junction IgG, C3 and C5b-C9 deposition. This effect is achieved by treating mice with 10 μg of anti-C1q antibody, twice weekly for 4 weeks. Treatment with a higher amount of anti-C1q antibody gives rise to increased serum anti-acetylcholine receptor antibody, immune complex and C3 levels, facilitates kidney C3 and IgG deposits and thus reduces the treatment efficacy. C4 KO and anti-C1q antibody treated mice display normal immune system functions and intact antibody production capacity. Furthermore, CCP inhibition preserves alternative complement pathway activation, which is required for host defense against microorganisms. Therefore, CCP inhibition might constitute a specific treatment approach for not only myasthenia gravis but also other complement mediated autoimmune diseases.
AB - Mice deficient for classical complement pathway (CCP) factor C4 are resistant to antibody and complement mediated experimental autoimmune myasthenia gravis (EAMG). Anti-C1q antibody administration before or following acetylcholine receptor immunization suppresses EAMG development by reducing lymph node cell IL-6 production and neuromuscular junction IgG, C3 and C5b-C9 deposition. This effect is achieved by treating mice with 10 μg of anti-C1q antibody, twice weekly for 4 weeks. Treatment with a higher amount of anti-C1q antibody gives rise to increased serum anti-acetylcholine receptor antibody, immune complex and C3 levels, facilitates kidney C3 and IgG deposits and thus reduces the treatment efficacy. C4 KO and anti-C1q antibody treated mice display normal immune system functions and intact antibody production capacity. Furthermore, CCP inhibition preserves alternative complement pathway activation, which is required for host defense against microorganisms. Therefore, CCP inhibition might constitute a specific treatment approach for not only myasthenia gravis but also other complement mediated autoimmune diseases.
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U2 - 10.1007/978-0-387-78952-1_19
DO - 10.1007/978-0-387-78952-1_19
M3 - Chapter
C2 - 19025128
AN - SCOPUS:58149349890
SN - 9780387789514
T3 - Advances in Experimental Medicine and Biology
SP - 265
EP - 272
BT - Current Topics in Complement II
PB - Springer New York
ER -