Table 1.
Pathogenicity and epitope specificity of human monoclonal anti-α3(IV)NC1 Ab after administration to XenoMouse II®
| mAb | n | BUN (SD) creatinine for F1.1∗ |
Albuminuria/proteinuria∗ |
GN |
C2 | C6 | |||
|---|---|---|---|---|---|---|---|---|---|
| pre |
post |
pre |
post |
H&E |
IF |
||||
| F2.1 | 4 | NA | 32 (7) | 31 (23) | 37 (10) | 1–2+ | 2+ | + | +++ |
| F3.1 | 8 | 32 (8) | 43 (10)∗ | 41 (22) | 47 (28) | 2–3+1 | 3+ | + | ++ |
| F1.1 | 8 | 0.007 | 0.424 | 1.6∗ | 340 (314)∗ | 2+ | 2+ | + | ++ |
| Polyclonal human | 2 | ND | ND | ND | ND | 2+ | 2+ | ND | ND |
In some short-tem experiments (5 days), normal mice were used, because of the limited availability of XenoMouse II. Grading of histopathologic findings: 0–1+ = normal or mild increase in cellularity; 2+ = glomerular enlargement and focal hypercellu-larity (increased matrix may be present in some); 3+ = focal hy-percellularity/proliferation in >50% of glomeruli with <30% diffuse proliferative changes and/or crescents; 4+ = diffuse prolif-erative changes with crescents/sclerosis in >50% of glomeruli. Epitope specificity was defined by competitive inhibition, using cyclic peptides corresponding to the C2 and C6 regions of α3(IV)NC1 (1 μg/well for mAb and 10 μg/well for serum-derived polyclonal anti-GBM Ab): + = 10–25%; ++ = 25–50%; +++ = >50%.
p < 0.05.
Early crescents present.