Tsurikisawa Naomi, Oshikata Chiyako, Tsuburai Takahiro, Sugano Satoshi, Nakamura Yoko, Shimoda Takuya, Tamama Shunpei, Adachi Ken, Horita Ayako, Saito Ikuo, Saito Hiroshi
Departments of Allergy and Respirology, Sagamihara, Kanagawa, Japan.
Department of Medical Gastroenterology, Sagamihara, Kanagawa, Japan.
BMC Immunol. 2015 Dec 29;16:75. doi: 10.1186/s12865-015-0138-4.
Chronic 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.
We 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.
Nine 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.
Eosinophilia 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.
在所有嗜酸性肉芽肿性多血管炎(EGPA)患者中,半数患者在EGPA发病前会出现慢性嗜酸性粒细胞性肺炎(CEP)或嗜酸性粒细胞性胃肠炎(EG),或两者兼有并伴有哮喘。目前尚不清楚是什么因素决定了哮喘后患有CEP或EG的患者是否会发展为EGPA。
我们研究了17例EGPA患者和12例患有CEP但未患EGPA的患者。我们在发病期和缓解期检测了血清细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)和血管内皮生长因子(VEGF),以及产生白细胞介素-17的外周血CD4(+) T细胞(Th17细胞)的百分比。我们还检查了黏膜下嗜酸性粒细胞的数量以及基底膜到隐窝和隐窝到隐窝的距离,以评估EGPA发病期和缓解期以及CEP发病期结肠黏膜下层的水肿情况。
12例(75.0%)CEP患者出现症状或内镜检查异常。EGPA发病期结肠黏膜下嗜酸性粒细胞计数和水肿程度高于缓解期或CEP发病期。EGPA发病期的Th17细胞(%)和血清ICAM-1水平高于CEP。在EGPA中,外周血Th17细胞(%)与血清ICAM-1水平、结肠黏膜下嗜酸性粒细胞计数和水肿变化程度显著相关;与血清VEGF水平呈负相关;但与VCAM-1水平无关。
EGPA中的嗜酸性粒细胞增多和结肠黏膜下水肿变化比CEP更明显。EGPA中血管炎的机制似乎与血清Th17细胞数量增加、ICAM-1水平升高和VEGF水平降低有关。