Intravenous immunoglobulin protects against experimental thrombotic microangiopathy.
BACKGROUND
Intravenous immunoglobulin (IVIG) has been utilized in several forms of vasculitis and has many potential mechanisms of action, including the inhibition of C3 activation. We have previously demonstrated that IVIG can reduce glomerular injury in a model of membranous nephropathy mediated by C5b-9 [1]. C5b-9 has also been shown to mediate the thrombotic microangiopathy (TMA) induced by antibody to glomerular endothelial cells leading to a hemolytic uremic syndrome-type lesion [2].


METHODS
To test the hypothesis that IVIG might be effective in treating antibody-induced TMA, male uninephrectomized rats underwent right renal artery perfusion with goat anti-rat glomerular endothelial cell (GEN) antibody (20 mg/kg). Sheep IgG (200 mg/kg) was administered either 30 minutes before the renal artery perfusion (group I, N = 6) or 30 minutes postperfusion (group II, N = 9). A third control group received phosphate-buffered saline (PBS; group III, N = 12). A survival biopsy was performed at 15 minutes, and the animals were sacrificed on day 2.


RESULTS
There were no significant differences in proteinuria or hematocrit between the groups. Animals pretreated with IVIG had significantly improved survival and renal function, which was associated with a decrease in glomerular C3 deposition. The protective effect of IVIG was abolished if the administration was delayed 30 minutes after perfusion.


CONCLUSIONS
IVIG is effective in reducing injury in experimental TMA only if given prophylactically. The effect is mediated by inhibition of local intraglomerular complement activation.
Jefferson
J A
JA
Division of Nephrology, University of Washington, Seattle, Washington, USA. ashley.jefferson@bch.n-i.nhs.uk
Suga
S I
SI
Kim
Y G
YG
Pippin
J
J
Gordon
K L
KL
Johnson
R J
RJ
Couser
W G
WG
D000818:Animals; D000936:Antigen-Antibody Complex; D003167:Complement Activation / Q000187:drug effects; D003176:Complement C3 / Q000032:analysis; D007105:Immune Complex Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D010477:Perfusion; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery
D000936:Antigen-Antibody Complex; D003176:Complement C3; D016756:Immunoglobulins, Intravenous