Severe FOXP3+ and naïve T lymphopenia in a non-IPEX form of autoimmune enteropathy combined with an immunodeficiency.
Severe FOXP3+ and naïve T lymphopenia in a non-IPEX form of autoimmune enteropathy combined with an immunodeficiency.
复制标题
非 IPEX 形式的自身免疫性肠病合并免疫缺陷，导致严重 FOXP3+ 和幼稚 T 淋巴细胞减少。
DOI：
10.1053/j.gastro.2007.02.034
复制
发表时间：
2007
期刊：
影响因子：
29.4
通讯作者：
A. Bandeira
中科院分区：
文献类型：
--
作者：
J. Zuber;M. Viguier;F. Lemaître;V. Senée;N. Patey;G. Elain;F. Geissmann;F. Fakhouri;L. Ferradini;C. Julier;A. Bandeira
背景与目的
BACKGROUND & AIMS
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is the best-characterized form of a rare entity called autoimmune enteropathy (AIE). IPEX syndrome is due to mutations in the FOXP3 gene, a transcription factor essential for the development and function of the natural regulatory CD25(+)CD4(+) T cells. We studied a female patient with a polyautoimmune AIE syndrome resembling a mild form of IPEX syndrome but associated with recurrent bacterial infections and mild hypogammaglobulinemia. We hypothesized that this syndrome combined a deficit of FOXP3(+) cells and other lymphocyte populations.
METHODS
We analyzed the major lymphocyte subsets and the FOXP3(+) regulatory system in blood samples obtained during the 2-year period that followed the last autoimmune manifestation.
RESULTS
The patient had severe naïve T lymphopenia and a major deficit of FOXP3(+)CD4(+) T cells, both in circulation and in the highly inflamed intestinal mucosa, but mutations in the FOXP3 locus were excluded. The blood FOXP3(+) pool was devoid of CD25(high) cells, but the few regulatory CD25(+) cells were functional. Intrinsic defects in the expression of CD25, FOXP3, and interleukin 2 were excluded. Upon activation, a small subset of cells, presumably committed to regulatory function, sustained expression of CD25 and FOXP3.
CONCLUSIONS
Peripheral T lymphopenia of both naïve and natural regulatory T cells might be the consequence of defective thymic production or the short life span of exported T cells. This case sheds new light in the etiology of autoimmune manifestations in T-cell immunodeficiencies and in the heterogeneity of AIE.