Immune defects in families and patients with xeroderma pigmentosum and trichothiodystrophy
Immune defects in families and patients with xeroderma pigmentosum and trichothiodystrophy
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色素性干皮病和毛发硫营养不良家族和患者的免疫缺陷
DOI：
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发表时间：
1992
影响因子：
4.6
通讯作者：
Miria Stefanini
中科院分区：
文献类型：
--
作者：
Erminia Mariani;A. Facchini;M. C. Honorati;Enzo Lalli;E. Berardesca;P. Ghetti;S. Marinoni;F. Nuzzo;G. C. B. A. Ricotti;Miria Stefanini
着色性干皮病(XP)是一种罕见的常染色体隐性遗传病，其特征是光敏，皮肤暴露部分癌症发生率高，修复紫外光的能力降低。--诱发DNA损伤。在毛发硫代营养不良(TTD)患者中也发现了XP突变之一(XP-D)，TTD是一种罕见的常染色体隐性遗传病，其特征是毛发脆弱、智力和身体发育迟缓、特殊的面部和鱼鳞病。然而，在这些患者中，没有证据表明皮肤肿瘤的发生率增加。由于细胞免疫功能受损被认为是XP患者癌症倾向的辅助因素，我们调查了5名XP患者、5名TTD患者及其父母和24名TTD亲属的免疫缺陷(S)的参与情况。检测外周血淋巴细胞表型、NK细胞杀伤活性、NK细胞与靶细胞的结合以及干扰素α和β对NK细胞活性的影响。XP患者外周血中CD3+和CD4+淋巴细胞的相对比例降低，而TTD患者无明显变化。XP患者及其母亲NK细胞裂解活性降低，但其父亲的NK细胞裂解活性正常。NK细胞活性在TTD家系中存在差异：5例患者及其亲属中有4例表现为低NK细胞活性，1个家系正常。在TTD家系成员中，经干扰素-α或干扰素-β孵育后，NK细胞活性升高，但始终未达到正常值。相比之下，在XP患者及其母亲中，在体外与干扰素-α或干扰素-β孵育后，缺陷几乎完全得到纠正。我们的研究表明，大多数TTD和XP患者的NK裂解活性受损，这种缺陷也存在于他们的家庭成员中。此外，XP患者的循环T细胞数量较少。这些多重异常，加上DNA修复缺陷，可能与XP患者癌症风险的增加有关。
Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by photosensitivity, a high incidence of cancer in sun‐exposed portions of the skin and a reduced capacity to repair the u.v. ‐induced DNA damage. One of the XP mutations (XP‐D) has also been identified in patients affected by trichothiodystrophy (TTD), a rare autosomal recessive disease characterized by brittle hair, mental and physical retardation, peculiar face and ichthyosis. However, in these patients there is no evidence of increased skin tumour incidence. Since an impairment of cell‐mediated immunity has been proposed as a co‐factor in the cancer proneness of XP patients, we investigated the involvement of immune defect(s) in five XP patients, five TTD patients, their parents, and 24 TTD relatives. We evaluated the phenotype of circulating lymphocytes, natural killer (NK) cell lytic activity, target cell binding of NK cells at single cell level and the effect of interferons (IFN)α and β on NK cell activity. The relative proportion of CD3+ and CD4+ circulating lymphocytes was reduced in XP but not in TTD patients. NK cell lytic activity was decreased in XP patients and their mothers, but their fathers showed normal lytic activity. NK activity varied among TTD families: four out of five patients and their relatives presented low NK cell activity, and one family was normal. In TTD family members, NK activity increased after incubation with IFN‐α or IFN‐β, but never reached normal values. In contrast, in XP patients and their mothers, the defect was almost completely corrected after in vitro incubation with IFN‐α or IFN‐β. Our study indicates impaired NK lytic activity in the majority of TTD and XP patients and that this defect is present also in members of their families. In addition, XP patients present a low number of circulating T cells. These multiple abnormalities, together with DNA repair defects, could be related to the increased cancer risk in XP patients.