Costa-Carvalho B T, de Moraes-Pinto M I, de Almeida L C, de Seixas Alves M T, Maia R P, de Souza R L, Barreto M, Lourenço L, Vicente A M, Coutinho A, Carneiro-Sampaio M
Disciplina de Imunologia Rua dos Otonis, São Paulo, SP, Brazil.
Scand J Immunol. 2008 Jul;68(1):85-91. doi: 10.1111/j.1365-3083.2008.02055.x. Epub 2008 May 15.
IPEX is a rare X-linked syndrome, with immune dysfunction, polyendocrinopathy and enteropathy. We describe an infant who died at the age of 11 months after developing eczema, severe diarrhoea, diabetes, hypothyroidism, thrombocytopenia and four episodes of septicaemia. Immunophenotyping of peripheral blood at 8 months revealed normal CD3+ T, CD4+ T and CD8+ T cell numbers, with low NK and B cells. CD4+ and CD8+ T lymphocytes showed remarkably low numbers and percentages of naïve cells and high numbers of memory CD4 and CD8 cells. At autopsy, an intense depletion of immune cells in thymus, spleen and lymph nodes was observed. No Hassall's corpuscles were found in thymus. Lymphocytic pancreatitis and intense villous atrophy with mucosal lymphocytic infiltration in small bowel were also seen. FOXP3 gene studies revealed a: C-->G substitution 3 bp upstream of exon 10, which prevents splicing between exons 9 and 10, likely resulting in a functionally altered or deficient protein. Florid clinical findings are usually observed in association of forkhead DNA-binding domain mutations. The intense depletion of naïve T cells we report suggest that depletion of immune cells might take place due to uncontrolled activation due to the absence of regulatory T cells.
免疫失调、多内分泌腺病、肠病、X连锁综合征（IPEX）是一种罕见的X连锁综合征。我们描述了一名11个月大的婴儿，在出现湿疹、严重腹泻、糖尿病、甲状腺功能减退、血小板减少和4次败血症发作后死亡。8个月时外周血免疫表型分析显示CD3 + T、CD4 + T和CD8 + T细胞数量正常，NK和B细胞数量低。CD4 +和CD8 + T淋巴细胞显示幼稚细胞数量和百分比极低，记忆性CD4和CD8细胞数量高。尸检时，观察到胸腺、脾脏和淋巴结中免疫细胞严重耗竭。胸腺中未发现哈氏小体。还可见淋巴细胞性胰腺炎以及小肠中伴有黏膜淋巴细胞浸润的严重绒毛萎缩。FOXP3基因研究显示，在第10外显子上游3 bp处有一个a：C→G替换，这阻止了第9和第10外显子之间的剪接，可能导致功能改变或缺陷的蛋白质。在叉头DNA结合域突变的情况下通常会观察到明显的临床症状。我们报告的幼稚T细胞严重耗竭表明，由于缺乏调节性T细胞导致的不受控制的激活，可能会发生免疫细胞的耗竭。
