High-dose intravenous immunoglobulin treatment activates complement in vivo.
Several complement modulating effects of high-dose intravenous immunoglobulins (IVIG) have been proposed from in vitro studies and experimental animal models. However, the in vivo effects of IVIG on plasma complement in humans are yet not known. We have investigated the in vivo effects of IVIG on complement in seven women with unexplained recurrent spontaneous abortion who were without evidence of autoimmune disease. Samples were obtained before and after the very first infusion of IVIG. There was a marked increase in immunoglobulin G (IgG) from (median and range) 12.4 (9.4-15.9) to 26.8 (22.4-30.0) g/l but no change in immunoglobulin A (IgA) or immunoglobulin M (IgM). A significantly increased complement activation was demonstrated using neoepitope-specific enzyme immunoassays to the activation products C3bc (median increased from 9.8 to 31.2 AU/ml), Bb (0.66-1.66 g/ml), C5a (10.5-12.7 ng/ml), and TCC (0.81-2.19 AU/ml) (P = 0.015 for all). There were no changes in antigenic concentrations of individual complement components or regulators (C1q, C4, C3, C1-inhibitor, C4b-binding protein) and no decrease in complement haemolytic activity (classical and alternative CH50), which were all within the normal range. The classical pathway activation products C1rs/C1-inhibitor complexes, C4bc and C4d were elevated in all patients before IVIG treatment and did not change significantly during treatment. In conclusion, IVIG induced a significant activation of complement in vivo.
Mollnes
T E
TE
Department of Immunology and Transfusion Medicine, Nordland Central Hospital, Bodø, Norway.
Høgåsen
K
K
De Carolis
C
C
Vaquero
E
E
Nielsen
E W
EW
Fontana
L
L
Perricone
R
R
D000026:Abortion, Habitual / Q000188:drug therapy / Q000517:prevention & control; D001798:Blood Proteins / Q000032:analysis / Q000187:drug effects; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology*; D003174:Complement C1 Inactivator Proteins / Q000032:analysis; D015922:Complement C1q / Q000032:analysis; D003176:Complement C3 / Q000032:analysis; D051561:Complement C3 Convertase, Alternative Pathway; D003179:Complement C3b / Q000032:analysis; D015932:Complement C3c / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D015936:Complement C5a / Q000032:analysis; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex / Q000032:analysis; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006023:Glycoproteins; D006801:Humans; D007136:Immunoglobulins / Q000097:blood / Q000187:drug effects; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000032:analysis; D011247:Pregnancy; D011256:Pregnancy Outcome; D011951:Receptors, Complement / Q000032:analysis; D012008:Recurrence; D012709:Serum Albumin / Q000032:analysis / Q000187:drug effects
D001798:Blood Proteins; D003174:Complement C1 Inactivator Proteins; D003176:Complement C3; D003181:Complement C4; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D010446:Peptide Fragments; D011951:Receptors, Complement; D012709:Serum Albumin; D015922:Complement C1q; D003179:Complement C3b; D015932:Complement C3c; D015936:Complement C5a; D051561:Complement C3 Convertase, Alternative Pathway