DOI: 10.5061/dryad.1zcrjdfqk
title: Association between IL-5 levels and the clinicopathological features of eosinophilic granulomatosis with polyangiitis

description: Objective: Eosinophilic granulomatosis with polyangiitis (EGPA)
 is one of the principal causes of vasculitic neuropathy. Recently,
 clinicopathological differences among patients with EGPA based on their
 anti-neutrophil cytoplasmic antibody (ANCA) status have been reported.
 Furthermore, the efficacy of mepolizumab (an anti-interleukin-5 (IL-5)
 antibody drug) for the treatment of patients with EGPA has been
 demonstrated. This study aimed to elucidate the significance of
 IL-5 on the clinicopathological features of EGPA. Methods: The clinical
 features and pathological findings of sural nerve biopsy specimens from 45
 patients with EGPA were examined.  Results: Of the 45 patients,
 26 (58%) exhibited elevated serum IL-5 levels, whereas 14 (31%)
 were positive for myeloperoxidase (MPO)-ANCA. MPO-ANCA
 positivity was observed more frequently in IL-5-negative patients than in
 IL-5-positive patients (27% vs. 37%, P = 0.5), although not statistically
 significant. Sural nerve biopsy revealed higher numbers of the
 following parameters in IL-5-positive patients compared with IL-5-negative
 patients: extravascular eosinophils in the epineurium (P &lt; 0.01),
 eosinophils in the lumen of epineurial vessels (P &lt; 0.001),
 eosinophils attached to epineurial vascular endothelial cells (P &lt;
 0.01), and epineurial vessels occluded by intraluminal eosinophils (P
 &lt; 0.05). In contrast, from the viewpoint of MPO-ANCA
 status, the destruction of vascular structures, suggestive of vasculitis,
 was more frequently observed in MPO-ANCA-positive than in
 MPO-ANCA-negative patients (P &lt; 0.05). Vessel walls that
 demonstrated fibrinoid necrosis were also more frequent in
 MPO-ANCA-positive patients (P &lt; 0.01). Conclusions: Our
 results suggest that in patients with EGPA, the pathogenesis of
 vasculitis was very closely related to their ANCA status, whereas
 eosinophil-associated tissue damage was provoked by IL-5.
description: <b>Supplementary figure e-1:</b> <b>A scatter diagram of serum IL-5 levels. </b> In this study, serum IL-5 was considered positive if IL-5 levels were not lower than the detection limit for the assay (3.9 pg/ml, Quantikine®, R&D Systems, Minneapolis, USA). We also examined serum IL-5 levels in 10 healthy control subjects and confirmed that IL-5 levels in all subjects were lower than the detection limit. Even if the cut off value is increased to 10.0 pg/ml, the result of this study were similar as shown in Supplementary table e-2. <b>Supplementary figure e-2:</b> <b>Pathologic findings in four groups in patients with EGPA.</b> Overall, classical findings suggestive of vasculitis were more likely to be found in MPO-ANCA-positive patients, irrespective of their IL-5 status, whereas eosinophil-associated vascular damage was more common in IL-5-positive patients, irrespective of their MPO-ANCA status. <b>Supplementary table e-1:</b> <b>Clinical features and pathological findings of sural nerve biopsy specimens from patients with EGPA with and without ANCA</b> <b>Supplementary table e-2:</b> <b>Clinical features and pathological findings of sural nerve biopsy specimens from patients with EGPA (The cut off value of IL-5 is 10.0 pg/ml)</b>