Combined administration of IgA and IgG anti-Thy-1 antibodies enhances renal inflammation in rats.
BACKGROUND
IgA nephropathy (IgAN) is the most common type of immunologically mediated glomerulonephritis (GN) and is characterized by deposition in the glomerular mesangium of IgA together with C3, C5b-9, and properdin. In patients, the codeposition of IgA together with IgG and/or IgM can lead to a more progressive course of disease. In Wistar rats, mesangial proliferative GN can be induced by the injection of mouse IgG anti-Thy-1 antibodies (ER4G). In contrast, the administration of mouse IgA anti-Thy-1 antibodies (ER4A) to rats results in isolated hematuria without detectable albuminuria and without detectable complement deposition.


METHODS
To investigate the effect of the combination of IgA and IgG on glomerular injury, Wistar rats were injected with a limiting dose of ER4G in the presence or absence of ER4A in a dose able to induce hematuria.


RESULTS
Although the limiting dose of ER4G or the dose of ER4A used did not induce significant albuminuria, the combination of ER4G and ER4A resulted in a synergistic increase in albuminuria. Microhematuria occurred in rats receiving either ER4A or ER4G alone or in combination. Although both ER4A or a limiting dose of ER4G induced minor increases in extracellular matrix expansion, the combination resulted in a pronounced, additive increased matrix expansion.


CONCLUSIONS
We conclude that in this model of IgA-mediated glomerulopathy, a selective complement-dependent synergistic renal injury is induced in Wistar rats by glomerular codeposition of mouse anti-Thy-1 monoclonal isotypes.
Van Dixhoorn
M G
MG
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. Dixhoorn@ch1.fgg.eur.nl
Sato
T
T
Muizert
Y
Y
Van Gijlswijk-Janssen
D J
DJ
de Heer
E
E
Daha
M R
MR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000378:metabolism; D004195:Disease Models, Animal; D005922:Glomerulonephritis, IGA / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007070:Immunoglobulin A / Q000008:administration & dosage* / Q000378:metabolism; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D051381:Rats; D017208:Rats, Wistar; D018800:Thy-1 Antigens
D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018800:Thy-1 Antigens