Universidade Estadual de Londrina (UEL), Londrina, PR, Brazil.
Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil.
Clin Immunol. 2015 Feb;156(2):131-40. doi: 10.1016/j.clim.2014.12.007. Epub 2014 Dec 27.
Early-life autoimmunity is an IPEX characteristic, however intrauterine forms had not yet been described. Here, two unrelated families with clear evidence of fetal-onset IPEX are reported. One had 5 miscarriages of males in two generations, and a newborn presenting type-1 diabetes mellitus immediately after birth, diarrhea, thrombocytopenia, eczematous dermatitis, eosinophilia, high IgE levels and autoantibodies to pancreatic islet antigens at 4-days-old. Maternal serology was negative. He presented a FOXP3 mutation, c.1189C>T, p.Arg397Trp, previously described only in another family with IPEX at birth. The second family had several miscarriages of males in three consecutive generations and a novel FOXP3 c.319_320delTC mutation was observed in two miscarried monochorionic twin male fetuses. These twins died at 21weeks of gestation due to hydrops, and CD3+ infiltrating lymphocytes were found in their pancreas. We demonstrate that: i) IPEX may develop in fetal life; and ii) c.1189C>T and c.319_320delTC mutations are associated with early-onset phenotype.
早发性自身免疫是 IPEX 的特征，但尚未描述宫内形式。在这里，报告了两个具有明确胎儿发作 IPEX 证据的无关家族。一个家族在两代中有 5 例男性流产，一个新生儿在出生后立即出现 1 型糖尿病、腹泻、血小板减少症、特应性皮炎、嗜酸性粒细胞增多症、高 IgE 水平和胰岛自身抗体。母亲的血清学检测为阴性。他携带了一个以前仅在另一个出生时就患有 IPEX 的家族中描述过的 FOXP3 突变，c.1189C>T，p.Arg397Trp。第二个家族在三代中有几次男性流产，在两个流产的单绒毛膜双胎男性胎儿中观察到了新的 FOXP3 c.319_320delTC 突变。这些双胞胎因水肿在 21 周的妊娠期死亡，其胰腺中发现了 CD3+浸润淋巴细胞。我们证明：i）IPEX 可能在胎儿期发展；ii）c.1189C>T 和 c.319_320delTC 突变与早发性表型相关。
