RESTRICTED HETEROGENEITY OF LYMPHOCYTES-T IN COMBINED IMMUNODEFICIENCY WITH HYPEREOSINOPHILIA (OMENNS SYNDROME)
RESTRICTED HETEROGENEITY OF LYMPHOCYTES-T IN COMBINED IMMUNODEFICIENCY WITH HYPEREOSINOPHILIA (OMENNS SYNDROME)
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DOI：
10.1172/jci115139
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发表时间：
1991-04-01
影响因子：
15.9
通讯作者：
FISCHER, A
中科院分区：
文献类型：
--
作者：
DESAINTBASILE, G;LEDEIST, F;FISCHER, A
我们报告了5例Omenn综合征患者的免疫学特征，Omenn综合征是一种罕见的遗传性免疫缺陷，也称为联合免疫缺陷伴嗜酸性粒细胞增多症。 该综合征的特征在于皮肤、肠道、肝脏和脾脏的T细胞浸润，导致弥漫性红皮病、长期腹泻、发育不良和肝脾肿大。 发现血液T细胞以及浸润皮肤和肠道的T细胞表达活化标记物，并且被有丝分裂原部分活化，但不被抗原活化。 尽管这些病变与移植物抗宿主病中的病变相似，但使用探针进行DNA单倍型分析显示血液T细胞，揭示了属于患者的可变数量的串联重复序列以及一名患者中浸润肠道和皮肤的T细胞。 给定的T细胞亚群（TCR-α-β +、CD 4 +/CD 8+或TCR-γ-δ +）在每例患者中占主导地位，在皮肤病变中具有特异性分布。 此外，在4名患者中进行的T细胞受体β、γ和δ基因重排研究揭示了涉及C-β-1、C-β-2或不同V-γ-J-γ或V-δ-J-δ基因的寡克隆性。 这表明先前在一例病例中报道的T细胞谱系的有限异质性是该综合征的主要特征。 其中一名患者的兄弟发生淋巴细胞增多症型严重联合免疫缺陷，这表明Omenn综合征中T细胞受体基因使用的有限异质性可能源于遗传决定的T细胞分化缺陷背景下的泄漏。
We report the immunological characteristics of five patients with Omenn's syndrome, a rare inherited immunodeficiency also known as combined immunodeficiency with hypereosinophilia. The syndrome is characterized by T cell infiltration of skin, gut, liver, and spleen leading to diffuse erythroderma, protracted diarrhea, failure to thrive, and hepatosplenomegaly. Blood T cells as well as those infiltrating the skin and gut were found to express activation markers and were partially activated by mitogens but not by antigens. Although the lesions resembled those in graft-versus-host disease, the blood T cells were shown by DNA haplotype analysis using probes revealing variable number of tandem repeats to belong to the patients as well as the T cells infiltrating the gut and skin in one patient. A given T cell subset (TCR-alpha-beta+, CD4+/CD8+, or TCR-gamma-delta+) was predominant in each patient, with a specific distribution in the skin lesions. Moreover, the study of T cell receptor-beta, gamma, and delta-gene rearrangements in four patients revealed oligoclonality involving C-beta-1, C-beta-2, or different V-gamma-J-gamma or V-delta-J-delta genes. This indicates that restricted heterogeneity of the T cell repertoire, previously reported in one case, is a major feature of this syndrome. The occurrence of alymphocytosis-type severe combined immunodeficiency in the brother of one of the patients suggests that the restricted heterogeneity of T cell receptor gene usage in Omenn's syndrome may arise from leakiness, within the context of a genetically determined faulty T cell differentiation.