SILVIA YUMI BANDO TAKAHARA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Pediatria, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
2 resultados
Resultados de Busca
Agora exibindo 1 - 2 de 2
- Intrauterine IPEX(2020) CARNEIRO-SAMPAIO, Magda; MOREIRA-FILHO, Carlos Alberto; BANDO, Silvia Yumi; DEMENGEOT, Jocelyne; COUTINHO, AntonioIPEX is one of the few Inborn Errors of Immunity that may manifest in the fetal period, and its intrauterine forms certainly represent the earliest human autoimmune diseases. Here, we review the clinical, histopathologic, and genetic findings from 21 individuals in 11 unrelated families, with nine different mutations, described as cases of intrauterine IPEX. Recurrent male fetal death (multigenerational in five families) due to hydrops in the midsemester of pregnancy was the commonest presentation (13/21). Noteworthy, in the affected families, there were only fetal- or perinatal-onset cases, with no affected individuals presenting milder forms with later-life manifestation. Most alive births were preterm (5/6). Skin desquamation and intrauterine growth restriction were observed in part of the cases. Fetal ultrasonography showed hyperechoic bowel or dilated bowel loops in the five cases with available imaging data. Histopathology showed multi-visceral infiltrates with T lymphocytes and other cells, including eosinophils, the pancreas being affected in most of the cases (11/21) and as early as at 18 weeks of gestational age. Regarding the nine FOXP3 mutations found in these cases, six determine protein truncation and three predictably impair protein function. Having found distinct presentations for the same FOXP3 mutation in different families, we resorted to the mouse system and showed that the scurfy mutation also shows divergent severity of phenotype and age of death in C57BL/6 and BALB/c backgrounds. We also reviewed age-of-onset data from other monogenic Tregopathies leading to IPEX-like phenotypes. In monogenic IPEX-like syndromes, the intrauterine onset was only observed in two kindreds with IL2RB mutations, with two stillbirths and two premature neonates who did not survive. In conclusion, intrauterine IPEX cases seem to constitute a particular IPEX subgroup, certainly with the most severe clinical presentation, although no strict mutation-phenotype correlations could be drawn for these cases.
- Inborn Errors of Immunity With Fetal or Perinatal Clinical Manifestations(2022) CARNEIRO-SAMPAIO, Magda; JESUS, Adriana Almeida de; BANDO, Silvia Yumi; MOREIRA-FILHO, Carlos AlbertoIn this article we revised the literature on Inborn Errors of Immunity (IEI) keeping our focus on those diseases presenting with intrauterine or perinatal clinical manifestations. We opted to describe our findings according to the IEI categories established by the International Union of Immunological Societies, predominantly addressing the immunological features of each condition or group of diseases. The main finding is that such precocious manifestations are largely concentrated in the group of primary immune regulatory disorders (PIRDs) and not in the group of classical immunodeficiencies. The IEI categories with higher number of immunological manifestations in utero or in perinatal period are: (i) diseases of immune dysregulation (HLH, IPEX and other Tregopathies, autosomal recessive ALPS with complete lack of FAS protein expression) and (ii) autoinflammatory diseases (NOMID/CINCA, DIRA and some interferonopathies, such as Aicardi-Goutieres syndrome, AGS, and USP18 deficiency). Regarding the other IEI categories, some patients with Omenn syndrome (an atypical form of SCID), and a few X-linked CGD patients present with clinical manifestations at birth associated to immune dysregulation. The most frequent clinical features were hydrops fetalis, intrauterine growth retardation leading to fetal loss, stillbirths, and prematurity, as in HLH and IPEX. Additionally, pseudo-TORCH syndrome was observed in AGS and in USP18 deficiency. The main goal of our review was to contribute to increasing the medical awareness of IEI with intrauterine and perinatal onset, which has obvious implications for diagnosis, treatment, and genetic counseling.