Association between IL-5 levels and the clinicopathological features of eosinophilic granulomatosis with polyangiitis

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 < 0.01),
eosinophils in the lumen of epineurial vessels (P < 0.001),
eosinophils attached to epineurial vascular endothelial cells (P <
0.01), and epineurial vessels occluded by intraluminal eosinophils (P
< 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 < 0.05). Vessel walls that
demonstrated fibrinoid necrosis were also more frequent in
MPO-ANCA-positive patients (P < 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.