ICPi accelerates autoantibody production and lupus erythematosus onset in young NZB mice. NZB mice (6-week-old females) were treated with ICPi (red) or PBS (blue) for 28 days. (A) Autoantibodies bound to peripheral CD41⁺ platelets, CD45⁺ white blood cells, and Ter119⁺ RBCs were assessed before and during ICPi treatment with a direct antiglobulin test by staining with anti-mouse Igs APC. (B) Hematocrit was evaluated before, during (at 14 days), and at the cessation of ICPi treatment (at 28 days). (C-D) Serum was collected to quantify double-stranded DNA (dsDNA) autoantibodies by enzyme-linked immunosorbent assay (ELISA) at ICPi treatment cessation (C) and blood urea nitrogen (BUN) and creatinine at the time of euthanasia (ie, 3 months after treatment cessation) (D). Kidneys from ICPi- and PBS-treated NZB mice were collected, formalin fixed, and paraffin embedded. Histologic findings in periodic acid–Schiff (PAS)-stained coronal kidney sections were analyzed. (E-F) Percent of total cortical parenchyma with interstitial inflammation, interstitial fibrosis/tubular atrophy (IFTA) (E), and the number of arteritis lesions per tissue section (F) was calculated. (G) Glomerular features including mesangial hypercellularity, mesangial deposits, endocapillary hypercellularity, leukocyte infiltration, subendoethlial and intracapillary deposits, crescents, and glomerulosclerosis were graded semiquantitatively on a scale of 0 to 3+ (0, absent; 1+, involving 1%-25% glomeruli; 2+, involving 26%-50% glomeruli; 3+, involving >50% glomeruli per coronal section of kidney containing >150 glomeruli per mouse). (H) Representative histologic PAS-stained kidney sections are shown. Data are cumulative from 2 independent experiments with 10 mice per group. Statistical significance was determined by Mann-Whitney test or repeated measures 2-way ANOVA with Sidak multiple comparisons test: ∗P < .05; ∗∗P < .01; ∗∗∗∗P < .0001. IgG, immunoglobulin G.