CHU de Montpellier, Service de Médecine Interne A, Hôpital Saint Eloi, Montpellier, France.
J Intern Med. 2013 Oct;274(4):351-62. doi: 10.1111/joim.12098. Epub 2013 Jul 4.
Hereditary haemorrhagic telangiectasia (HHT) is a genetic disorder related to mutations in one of the coreceptors to the transforming growth factor-β superfamily (ALK1 or endoglin). Besides the obvious vascular symptoms (epistaxis and arteriovenous malformations), patients have an unexplained high risk of severe bacterial infections. The aim of the study was to assess the main immunological functions of patients with HHT using the standard biological tests for primary immunodeficiencies.
DESIGN, SETTING AND SUBJECTS: A prospective single-centre study of 42 consecutive adult patients with an established diagnosis of HHT was conducted at the National French HHT Reference Center (Lyon). Lymphocyte subpopulations and proliferation capacity, immunoglobulin levels and neutrophil and monocyte phagocytosis, oxidative burst and chemotaxis were assessed.
Innate immunity was not altered in patients with HHT. With regard to adaptive immunity, significant changes were seen in immunological parameters: primarily, a lymphopenia in patients with HHT compared with healthy control subjects affecting mean CD4 (642 cells μL(-1) vs. 832 cells μL(-1) , P < 0.001), CD8 (295 cells μL(-1) vs. 501 cells μL(-1) , P < 0.0001) and natural killer (NK) cells (169 cells μL(-1) vs. 221 cells μL(-1) , P < 0.01), associated with increased levels of immunoglobulins G and A. This lymphopenia mainly concerned naïve T cells. Proliferation capacities of lymphocytes were normal. Lymphopenic patients had a higher frequency of iron supplementation but no increase in infection rate. Lower levels of immunoglobulin M and a higher rate of pulmonary arteriovenous malformations were found amongst patients with a history of severe infection.
Patients with HHT exhibit immunological abnormalities including T CD4, T CD8 and NK cell lymphopenia and increased levels of immunoglobulins G and A. The observed low level of immunoglobulin M requires further investigation to determine whether it is a specific risk factor for infection in HHT.
遗传性出血性毛细血管扩张症（HHT）是一种与转化生长因子-β超家族的一个核心受体（ALK1 或内皮糖蛋白）突变相关的遗传疾病。除了明显的血管症状（鼻出血和动静脉畸形）外，患者还存在不明原因的严重细菌感染风险增加。本研究的目的是使用原发性免疫缺陷症的标准生物学检测方法评估 HHT 患者的主要免疫功能。
设计、设置和对象：在法国国家 HHT 参考中心（里昂）进行了一项前瞻性、单中心研究，纳入了 42 例确诊为 HHT 的连续成年患者。评估了淋巴细胞亚群和增殖能力、免疫球蛋白水平以及中性粒细胞和单核细胞吞噬作用、氧化爆发和趋化性。
HHT 患者的固有免疫未改变。关于适应性免疫，免疫参数发生了显著变化：首先，与健康对照组相比，HHT 患者存在淋巴细胞减少，主要影响平均 CD4（642 个细胞/μL 对 832 个细胞/μL，P < 0.001）、CD8（295 个细胞/μL 对 501 个细胞/μL，P < 0.0001）和自然杀伤（NK）细胞（169 个细胞/μL 对 221 个细胞/μL，P < 0.01），同时免疫球蛋白 G 和 A 水平升高。这种淋巴细胞减少主要涉及幼稚 T 细胞。淋巴细胞的增殖能力正常。淋巴细胞减少的患者铁补充剂的频率更高，但感染率没有增加。在有严重感染史的患者中，发现免疫球蛋白 M 水平较低和肺动静脉畸形发生率较高。
HHT 患者存在免疫异常，包括 CD4、CD8 和 NK 细胞淋巴细胞减少和免疫球蛋白 G 和 A 水平升高。观察到的免疫球蛋白 M 水平较低需要进一步调查，以确定其是否是 HHT 感染的特定危险因素。
