Department of Paediatric Research, Oslo University Hospital, Oslo, Norway.
Department of Paediatric Medicine, Oslo University Hospital, Oslo, Norway.
J Clin Immunol. 2019 Jan;39(1):65-74. doi: 10.1007/s10875-018-0579-7. Epub 2018 Dec 19.
Immunodeficiency is one of the key features of 22q11.2 deletion syndrome (del), and it is seen in approximately 75% of the patients. The degree of immunodeficiency varies widely, from no circulating T cells to normal T cell counts. It has been hypothesized that the low number of T cells may at least in part be due to increased apoptosis of T cells. Increased spontaneous T cell apoptosis has been reported in one patient with 22q11.2del, but this has not been further investigated.
A national cohort of patients with a proven heterozygous deletion of chromosome 22q11.2 diagnosed by FISH or MLPA and a group of age and sex matched controls were studied. Spontaneous and activation-induced apoptosis, in addition to FAS expression on lymphocytes, were measured using flow cytometry. Serum levels of FASL were analyzed using ELISA.
There was no increased spontaneous apoptosis in patients with 22q11.2del. Upon activation, anti-FAS-induced apoptosis was significantly increased in patients compared to those in controls, while there was no difference in activation induced cell death or activated cell autonomous death. We also found a significant increase in expression of FAS on freshly isolated lymphocytes from patients, while there was no difference in serum levels of FASL. Patients with congenital heart defects (CHD) had significantly higher serum levels of FASL compared to non-CHD patients.
We have shown increased FAS expression on lymphocytes from patients with 22q11.2del as well as increased levels of FASL in patients with CHD. Those changes may contribute to the pathophysiology of the 22q11.2del.
免疫缺陷是 22q11.2 缺失综合征（del）的一个关键特征，约 75%的患者存在免疫缺陷。免疫缺陷的程度差异很大，从无循环 T 细胞到正常 T 细胞计数。有人假设，T 细胞数量减少至少部分是由于 T 细胞凋亡增加所致。已有报道称，一名 22q11.2del 患者的 T 细胞自发性凋亡增加，但尚未进一步研究。
我们研究了一组经 FISH 或 MLPA 证实存在染色体 22q11.2 杂合性缺失的患者（n=11），并与一组年龄和性别匹配的对照组进行了比较。使用流式细胞术测量了淋巴细胞的自发性和激活诱导凋亡，以及 FAS 表达。使用 ELISA 分析了血清中 FASL 的水平。
22q11.2del 患者的自发性凋亡没有增加。与对照组相比，抗 FAS 诱导的凋亡在患者中显著增加，而激活诱导的细胞死亡或激活的细胞自主死亡无差异。我们还发现，与对照组相比，患者新鲜分离的淋巴细胞上 FAS 的表达显著增加，而血清中 FASL 的水平无差异。患有先天性心脏病（CHD）的患者的血清 FASL 水平明显高于非 CHD 患者。
我们发现 22q11.2del 患者的淋巴细胞上 FAS 表达增加，以及 CHD 患者的 FASL 水平升高。这些变化可能导致 22q11.2del 的病理生理变化。
