Th17 cells reflect colon submucosal pathologic changes in active eosinophilic granulomatosis with polyangiitis

Abstract

BackgroundChronic eosinophilic pneumonia (CEP) or eosinophilic gastroenteritis (EG), or both, with asthma precede the onset of eosinophilic granulomatosis with polyangiitis (EGPA) in half of all EGPA patients. It is not known what determines whether patients with CEP or with EG following asthma will develop EGPA.MethodsWe studied 17 EGPA patients and 12 patients with CEP but without EGPA. We assayed serum ICAM-1, VCAM-1, and VEGF, and the percentage of peripheral blood CD4+ T cells producing IL-17 (Th17 cells), at both onset and remission. We also examined the numbers of submucosal eosinophils and the basement membrane-to-crypt and crypt-to-crypt distance to evaluate edema in the colon submucosa at onset and remission in EGPA and at onset in CEP.ResultsNine of 12 (75.0 %) CEP patients had symptoms or endoscopic findings. Colonic submucosal eosinophil counts and edema in EGPA at onset were greater than at remission or in CEP at onset. Th17 cells (%) and serum ICAM-1 levels at onset were greater in EGPA than in CEP. In EGPA, peripheral blood Th17 cells (%) were significantly correlated with serum ICAM-1 level, colonic submucosal eosinophil count, and degree of edematous change; inversely correlated with serum VEGF level; but not correlated with VCAM-1 level.ConclusionsEosinophilia and colonic submucosal edematous change were greater in EGPA than in CEP. The mechanism of vasculitis in EGPA appears related to increases in serum Th17 cell numbers and ICAM-1 levels and decreases in VEGF levels.

Innate immune response reflects disease activity in eosinophilic granulomatosis with polyangiitis

“…Previously, we reported that the number of inducible T reg cells (CD4 + T cells producing IL-10) in peripheral blood was comparable in patients with active CEP or EGPA at onset 6 and that the number of T helper 17 cells (CD4 + T cells producing IL-17) was comparable in patients with active or inactive CEP or EGPA at onset or relapse. 43 We have also reported that the percentage of CD4 + CD25 + T cells (T reg cells) was correlated with the number of inducible T reg cells (IL-10-producing cells) or naturally occurring T reg cells (FOXP3 + CD4 + ) in patients with EGPA. 51 In addition, we have reported that the percentage of CD83 + dendritic cells, which are mature dendritic cells, was significantly correlated with the number of naturally occurring or inducible T reg cells (CD4 + CD25 + T cells producing IL-10) or the number of TGF-β cells, but not the number of eosinophils in patients with EGPA.…”

“…7 Previously, we reported a higher serum vascular cell adhesion protein 1 concentration and lower serum vascular endothelial growth factor concentration in patients with EGPA at onset. 43 We hypothesized that angiogenesis and vascular permeability is promoted by endothelial cells activated by IL-33. 22 We also hypothesize that serum IL-33 concentration might be reflected in the disease activity or severity of EGPA.…”

“…Gastrointestinal involvement was defined as symptoms of epigastralgia, abdominal pain, diarrhea, or constipation, or as positive endoscopic signs and gastrointestinal eosinophil infiltration or colonic submucosal edematous change, 43 as detected by biopsy. Skin involvement was defined as purpura, erythema, livedo, ulceration, acrocyanosis, nodule formation, or eosinophil infiltration, as detected by biopsy.…”

Developmental endothelial locus‐1 (Del‐1) antagonizes Interleukin‐17‐mediated allergic asthma

“…9,10 In addition, IL-17 enhances eosinophilic recruitment during airway inflammation in allergic asthma. 11,12 Hence, there might be clinical benefit by inhibiting IL-17 immunity.…”

The significance of cutaneous manifestations in EGPA (eosinophilic granulomatosis with polyangiitis)

“…A szöveti károsodásban fontos szerepet játszik a kóros ANCA jelenléte és a következményes neutrophil aktiváció (8). Az újabb irodalmi adatok a fokozott IL-17A termelődésre is felhívják a figyelmet, ami a granuloma képződésében szerepet játszhat (9).…”