Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: A systematic review

Park, Jae Hyon; Lee, Keum Hwa; Jeon, Bokyoung; Ochs, Hans D.; Lee, Joon Suk; Gee, Heon Yung; Seo, Seeun; Geum, Dongil; Piccirillo, Ciriaco A.; Eisenhut, Michael; Vliet, Hans J. van der; Lee, Jiwon M.; Kronbichler, Andreas; Ko, Yun Woong; Smıth, Lee

doi:10.1016/j.autrev.2020.102526

Cited by 64 publications

(58 citation statements)

References 84 publications

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“…Exon stratification showed the majority of the mutations lying in the functional domains, particularly in the exons coding for the FHK, leucine zipper, and repressor N-terminal domains. These data were confirmed by a recently published study on exon stratification of FOXP3 mutations (14). Finally, a revision of 70 different FOXP3 mutations accomplished by Bachetta et al (23) concluded for a lack of genotype-phenotype correlation in IPEX, although drawing attention to specific mutations, such as c.1189 C > T, associated to fetal or neonatal death in several patients.…”

Section: Foxp3 Mutations and Genotype-phenotype Correlations In Ipexmentioning

confidence: 73%

“…Regarding unusual manifestations, there were three fetuses with dysmorphic features (clubfeet, clinodactyly, equinovarus, and micrognathia) among the individuals here analyzed, but they also presented pathogenic variants of other autosomal genes (7,10). Dysmorphisms and malformations have not been described in the IPEX babies (3,14). Akinesia was another rare manifestation described in one fetus at 18 weeks of gestational age, whose necropsy showed a near absent skeletal muscle, that was replaced by fibrosis tissue and macrophages (9).…”

Section: Clinical Imaging and Histopathologic Features Of Intrautermentioning

confidence: 74%

“…Regarding the organ and tissue targets in intrauterine IPEX, the most frequent observations have been: (i) the pancreas was infiltrated by T-lymphocytes in most fetuses examined as early as 18 weeks of gestational age, (ii) the gut was affected in all fetal and stillbirth cases with available ultrasound data, (iii) cutaneous manifestations were described in five out of 21 individuals with clinical data available ( Table 1), and (iv) hemolytic anemia as the possible origin of fetal hydrops and death of most individuals represent the most intriguing feature since its frequency would be high in this particular IPEX group. A recent review of 195 IPEX patients revealed that 191 (97.9%) presented enteropathy, 121 (62.1%) had skin manifestations, 104 (53.3%) manifested endocrinopathies, and in only 75 (38.5%) hematologic abnormalities were detected (14), reinforcing the classic IPEX clinical triad. In other words, the characteristic targets of IPEX polyautoimmunity are similar, while the respective frequencies are quite different, comparing intrauterine-onset cases with the post-natal "conventional" IPEX, for reasons not fully understood yet.…”

Section: Discussionmentioning

confidence: 94%

“…Progressive CNS2 demethylation occurs along thymic Treg cell development (26). Considering that alternative splicing and epigenetic regulation depend on the integrity of FOXP3 intronic regions, it explains why some patients with intronic mutations have reduced FOXP3 expression and mild to severe forms of IPEX (14,27,28).…”

Section: Foxp3 and Ipexmentioning

confidence: 99%

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Intrauterine IPEX

et al. 2020

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IPEX 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.

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Section: Foxp3 Mutations and Genotype-phenotype Correlations In Ipexmentioning

confidence: 73%

Section: Clinical Imaging and Histopathologic Features Of Intrautermentioning

confidence: 74%

Section: Discussionmentioning

confidence: 94%

Section: Foxp3 and Ipexmentioning

confidence: 99%

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Intrauterine IPEX

et al. 2020

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“…Part of the reason for the Chinese scholars focus on TCM when publishing in Chinese medical journals is the difficulty Chinese scholars have to disseminate their findings using modern scientific terminology/theory, compared to rather ancient theory of TCM, e.g., balance of Ying and Yang. Actually, we believe that balance of Ying and Yang is equivalent to the modern theory of anti-vs. pro-inflammatory responses in the micro-environment, i.e., imbalance of anti-vs. pro-inflammatory responses contributes to autoimmune diseases (54). Thus, from the point of view of the management of COVID-19, the efforts should be focused on the suppression of the SARS-CoV-2 virus, disregarding the backgrounds, theories, and approaches of modern vs. traditional scientific ideology.…”

Section: Discussionmentioning

confidence: 99%

Bibliometric Analysis on COVID-19: A Comparison of Research Between English and Chinese Studies

Fan

Gao

Zhao

et al. 2020

Front. Public Health

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Background: As an emerging infectious disease, COVID-19 has garnered great research interest. We aimed to explore the differences between English language and Chinese language Medical/Scientific journals publications, particularly aiming to explore the efficacy/contents of the literature published in English and Chinese in relation to the outcomes of management and characterization of COVID-19 during the early stage of COVID-19 pandemic. Methods: Publications on COVID-19 research were retrieved from both English and Chinese databases. Bibliometric analyses were performed using VOSviewer 1.6.14, and CiteSpace V software. Network maps were generated to evaluate the collaborations between different authors, countries/provinces, and institutions. Results: A total of 143 English and 721 Chinese original research articles and reviews on COVID-19 were included in our study. Most of the authors and institutions of the papers were from China before March 1st, 2020, however, the distribution of authors and institutions were mainly in developed countries or more wealthy areas of China. The range of the keywords in English publications was more extensive than those in Chinese. Traditional Chinese Medicine was seen more frequently in Chinese papers than in English. Of the 143 articles published in English, 54 articles were published by Chinese authors only and 21 articles were published jointly by Chinese and other overseas authors. Conclusions: The publications in English have enabled medical practitioners and scientists to share/exchange information, while on the other hand, the publications in the Chinese language have provided complementary educational approaches for the local medical practitioners to understand the essential and key information to manage COVID-19 in the relatively remote regions of China, for the general population with a general level of education.

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Prenatal Diagnosis of Primary Immunodeficiency Diseases

Puck

2021

Genetic Disorders and the Fetus

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Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: A systematic review

Cited by 64 publications

References 84 publications

Intrauterine IPEX

Intrauterine IPEX

Bibliometric Analysis on COVID-19: A Comparison of Research Between English and Chinese Studies

Prenatal Diagnosis of Primary Immunodeficiency Diseases

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