基因中的突变与白塞病肠道表型及治疗难治性之间可能存在的关联。

Possible Association of Mutations in the Gene with the Intestinal Phenotype of Behçet's Disease and Refractoriness to Treatment.

作者信息

Furuta Yoki, Gushima Ryosuke, Naoe Hideaki, Honda Munenori, Tsuruta Yuiko, Nagaoka Katsuya, Watanabe Takehisa, Tateyama Masakuni, Fujimoto Nahoko, Hirata Shinya, Miyagawa Eiko, Sakata Komei, Mizuhashi Yumiko, Iwakura Mikako, Murai Masayuki, Matsuoka Masao, Komohara Yoshihiro, Tanaka Yasuhito

机构信息

Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.

Department of Hematology, Rheumatology and Infectious Diseases, School of Medicine, Kumamoto University, Kumamoto 860-8556, Japan.

出版信息

J Clin Med. 2023 Apr 26;12(9):3131. doi: 10.3390/jcm12093131.

DOI:10.3390/jcm12093131

PMID:37176572

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10179346/

Abstract

BACKGROUND

Mediterranean fever () gene mutations are responsible for familial Mediterranean fever (FMF) and associated with other inflammatory diseases. However, the effects of gene mutations on intestinal Behçet's disease (BD) are unknown. In this study, we investigated these mutations and clinical features in patients with intestinal BD.

METHODS

gene analysis was performed in 16 patients with intestinal BD, 10 with BD without intestinal lesions, and 50 healthy controls. Clinical features of patients with intestinal BD were retrospectively assessed.

RESULTS

The rates of gene mutations in patients with intestinal BD, BD without intestinal lesions, and healthy controls were 75%, 50%, and 38%, respectively. Only 2 of 12 patients with intestinal BD harboring gene mutations (17%) were controlled without immunosuppressive treatment, while 8 patients (67%) required therapy with tumor necrosis factor (TNF) inhibitors. Among patients with intestinal BD without gene mutations (four patients), three (75%) were controlled by the administration of 5-aminosalicylic acid with or without colchicine, and one (25%) required TNF inhibitors. All patients who underwent intestinal resection had gene mutations. Immunohistochemical analysis and in situ hybridization with interleukin-1β (IL-1β) showed a high expression of IL-1β only in injured areas, suggesting that IL-1β may be involved in the formation of ulcers in patients with intestinal BD carrying gene mutations.

CONCLUSION

Mutations in the gene may be associated with intestinal lesions of BD and refractoriness to treatment.

摘要

背景

地中海热（）基因突变是家族性地中海热（FMF）的病因，并与其他炎症性疾病相关。然而，该基因突变对肠道白塞病（BD）的影响尚不清楚。在本研究中，我们调查了肠道BD患者的这些突变及临床特征。

方法

对16例肠道BD患者、10例无肠道病变的BD患者及50例健康对照者进行基因分析。对肠道BD患者的临床特征进行回顾性评估。

结果

肠道BD患者、无肠道病变的BD患者及健康对照者的基因突变率分别为75%、50%和38%。12例携带基因突变的肠道BD患者中，仅2例（17%）在未接受免疫抑制治疗的情况下病情得到控制，而8例（67%）需要使用肿瘤坏死因子（TNF）抑制剂进行治疗。在无基因突变的肠道BD患者（4例）中，3例（75%）通过使用5-氨基水杨酸加或不加秋水仙碱得到控制，1例（25%）需要使用TNF抑制剂。所有接受肠道切除术的患者均有基因突变。白细胞介素-1β（IL-1β）的免疫组织化学分析和原位杂交显示，IL-1β仅在损伤区域高表达，提示IL-1β可能参与携带基因突变的肠道BD患者溃疡的形成。