Increased Prevalence of Inflammatory Bowel Disease in Patients with Mutations in Genes Encoding the Receptor Subunits for TGFβ.
Increased Prevalence of Inflammatory Bowel Disease in Patients with Mutations in Genes Encoding the Receptor Subunits for TGFβ.
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DOI：
10.1097/mib.0000000000000872
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发表时间：
2016-09
影响因子：
4.9
通讯作者：
Dietz HC
中科院分区：
文献类型：
--
作者：
Guerrerio AL;Frischmeyer-Guerrerio PA;Huang C;Wu Y;Haritunians T;McGovern DPB;MacCarrick GL;Brant SR;Dietz HC
TGFβ是一种多功能细胞因子，在调节粘膜免疫中起关键作用。小鼠研究表明，典型TGFβ信号的破坏可导致包括结肠炎在内的全身性炎症。Loeys-Dietz综合征（LDS）是由编码TGFβ受体亚基的基因杂合突变引起的，所有在约翰霍普金斯结缔组织疾病诊所发现的TGFBR1或TGFBR2基因突变的患者都被要求参加这项研究。连续入组93例患者，包括4例IBD患者。使用Illumina免疫芯片阵列，我们进行了一项探索性分析，以评估可以预测哪些LDS患者会发展为IBD的潜在遗传风险因素。我们报告I型和II型Loeys-Dietz综合征患者IBD患病率增加。我们描述几个病人的病程。在这个小样本中，三名患有IBD的白种人的遗传风险评分（GRS）在评估的患者中排名前六。我们报告，与一般人群相比，LDS患者的IBD患病率增加了10倍。4名患者中有3名发病时间不到18年，其中2名的临床病程严重，对传统药物的反应不佳。需要对GRS进行进一步评估，以确定它是否可以预测哪些LDS患者最有可能发展为IBD。这一系列LDS合并IBD的病例表明，TGFβ信号缺陷可能对IBD风险有影响。
TGFβ is a multifunctional cytokine that is critical in regulating mucosal immunity. Murine studies have revealed that disruption of canonical TGFβ signaling leads to systemic inflammation including colitis. Loeys-Dietz syndrome (LDS) results from heterozygous mutations in the genes encoding the subunits of the TGFβ receptor All patients with confirmed mutations in TGFBR1 or TGFBR2, seen in the Johns Hopkins Connective Tissue Disorders clinic were asked to participate in the study. Ninety-three consecutive patients were enrolled, including 4 with IBD. Using the Illumina Immunochip array, we undertook an exploratory analysis to evaluate the potential genetic risk factors that could predict which LDS patients would develop IBD. We report an increased prevalence of IBD in patients with Loeys-Dietz syndrome types I and II. We describe the course of several patients. In this small sample, the three Caucasians with IBD had a genetic risk score (GRS) in the top six highest scores of patients evaluated. We report a 10-fold increase in the prevalence of IBD in LDS patients compared to the general population. Onset of disease in three of the four patients was at less than 18 years and the clinical course in two of the four was severe with a poor response to traditional medications. Further evaluation of the GRS is needed to determine if it can predict which LDS patients are most likely to develop IBD. This case series of LDS patients with IBD suggests that defective TGFβ signaling may have an influence on IBD risk.