We investigated whether serum aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP1) could predict severe cases of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) based on the Birmingham vasculitis activity score (BVAS). Sixty-one patients with AAV were selected for inclusion from our prospective AAV cohort. AAV-specific indices and clinical manifestations were assessed, and laboratory tests were performed on the day of blood sampling. Patients with severe AAV were defined as those with a BVAS higher than the lower limit of the highest tertile of BVAS (BVAS ≥ 12). We measured serum AIMP1 levels of the stored serum samples. A total of 20 (32.8%) and 41 (67.2%) patients were classified as having severe and nonsevere AAV according to the cut-off of BVAS ≥ 12. Patients with severe AAV showed higher frequencies of general and renal manifestations, along with ANCA positivity, and exhibited a higher mean neutrophil count, erythrocyte sedimentation rate, and C-reactive protein levels, but lower mean haemoglobin and serum albumin levels than those with nonsevere AAV. The mean serum AIMP1 level in patients with severe AAV was significantly higher than that of patients with nonsevere AIMP1 (351.1 vs. 98.4 pg/mL, p = 0.006). Multivariate logistic regression analysis including variables showing significance in univariate analyses revealed that only serum AIMP1 exhibited a significant association with severe AAV (odds ratio 1.004, p = 0.031). When we set the optimal cut-off of serum AIMP1 for severe AAV to 50.28 pg/mL, patients with severe AAV more frequently had AIMP1 levels above the cut-off than those with nonsevere AAV (80.0% vs. 31.7%, relative risk 8.615, p < 0.001). The results from our study suggest that serum AIMP1 can be used to estimate the cross-sectional severe AAV population based on the BVAS.

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Stem cell factor (SCF) and its receptor, cKIT, are novel regulators of pathological neovascularization in the eye, which suggests that inhibition of SCF/cKIT signaling may be a novel pharmacological strategy for treating neovascular age-related macular degeneration (AMD). This study evaluated the therapeutic potential of a newly developed fully human monoclonal antibody targeting cKIT, NN2101, in a murine model of neovascular AMD. In hypoxic human endothelial cells, NN2101 substantially inhibited the SCF-induced increase in angiogenesis and activation of the cKIT signaling pathway. In a murine model of neovascular AMD, intravitreal injection of NN2101 substantially inhibited the SCF/cKIT-mediated choroidal neovascularization (CNV), with efficacy comparable to aflibercept, a vascular endothelial growth factor inhibitor. A combined intravitreal injection of NN2101 and aflibercept resulted in an additive therapeutic effect on CNV. NN2101 neither caused ocular toxicity nor interfered with the early retinal vascular development in mice. Ocular pharmacokinetic analysis in rabbits indicated that NN2101 demonstrated a pharmacokinetic profile suitable for intravitreal injection. These findings provide the first evidence of the potential use of the anti-cKIT blocking antibody, NN2101, as an alternative or additive therapeutic for the treatment of neovascular AMD.