Phenotypic Characterization of Very Early-Onset Inflammatory Bowel Disease with Interleukin-10 Signaling Deficiency: Based on a Large Cohort Study

Zheng, Cuifang; Huang, Ying; Hu, Wenhui; Shi, Junjun; Qian, Xiaowen; Huang, Zhiheng; Xue, Aijuan; Wang, Yuhuan; Lu, Jincheng; Tang, Zifei; Wu, Jie; Wang, Lin; Peng, Kaiyue; Zhou, Ying; Miao, Shijian; Sun, Huaiqiang

doi:10.1093/ibd/izy289

Cited by 37 publications

(54 citation statements)

References 40 publications

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“…Since the initial report patients with IL10R signaling defects in 2009 by Glocker et al [8], more than 130 VEO-IBD patients with IL-10 or IL-10R gene mutations have been reported [10,11]. Most patients were from Europe and Asian, where IL-10R mutations were more frequent than IL-10 mutations.…”

Section: Discussionmentioning

confidence: 99%

“…In general, VEO-IBD patients with IL-10RA mutations suffered from even more complicated, severe, and intractable disease. They were characterized by very early onset symptoms, common perianal diseases (abscess, stulas, ssure, skin tag) and extra-intestinal manifestations, such as skin rash and oral ulcers, respond poorly to traditional treatment, and high surgery rate and mortality [11].…”

Section: Discussionmentioning

confidence: 99%

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Phenotype of Very-Early-Onset Inflammatory Bowel Disease with Interleukin-10 Receptor A Mutations in 22 Chinese Children

Guan¹,

Zhang²,

Guo³

et al. 2020

Preprint

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Backgroud: Very-early-onset inflammatory bowel disease (VEO-IBD) with onset in infancy may be caused by genetic mutation. We collected the VEO-IBD patients with interleukin-10 receptor A (IL-10RA) gene mutations to investigate the clinical phenotype and genetic characteristics.Methods: The data of 22 patients with VEO-IBD with IL-10RA gene mutations were retrospectively analyzed, and high-throughput sequencing was used to identify IL-10RA gene mutations.Results: All 22 patients in this study had IL-10RA gene mutations, including 4 (18.2%) homozygous mutations and 18 (81.8%) compound heterozygous mutations. Among these mutations, 10 mutations had been previously described and 1 novel mutation was identified. In these patients, c.C301T (p.R101W) (86.4%, 19/22) and c.G537A (p.T179T) (36.4%, 8/22) mutations were the most common mutations. This study showed that the patients had extremely early onset of symptoms, about 81.8% (18/22) of the patients had onset within 1 month after birth, and the onset time was 8.5 (IQR: 3.0–24.0) days. In addition, 77.3% (17/22) of patients had recurrent perianal lesions. Oral ulcers and skin rash were common extra-intestinal manifestations, accounting for 72.7% (16/22) and 63.6% (14/22), respectively. In this study, 3 patients underwent enterostomy and 1 patient experienced intestinal perforation repair. Umbilical cord blood transplantation (UCBT) and thalidomide proved efficacious. Follow-up showed the mortality rate was as high as 45% (9/20).Conclusions: We should consider the genetic defects in the IL-10 signaling pathway in VEO-IBD patients, particularly when they had early onset of symptoms, perianal lesions and severe colitis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Phenotype of Very-Early-Onset Inflammatory Bowel Disease with Interleukin-10 Receptor A Mutations in 22 Chinese Children

Guan¹,

Zhang²,

Guo³

et al. 2020

Preprint

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“…Pathologically, their colonic tissues are affected, accompanied by multiple perianal diseases. These, together with resistant to standard medical therapies, lead to a high mortality in China ( Huang et al, 2017 ; Zheng et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…Umbilical cord blood is a rich source of hematopoietic stem cells, and umbilical cord blood transplantation (UCBT) has been used for treatment of malignant and nonmalignant diseases to re-establishment of the hematopoietic system and correct immunodeficiency ( Frassoni et al, 2003 ; Munoz et al, 2014 )._ENREF_5 Previous studies have shown that UCBT with reduced-intensity conditioning has represented a curable treatment for patients with IL10RA -associated immune deficiency, making it a potential treatment for IBD ( Uhlig and Muise, 2017 ; Ye et al, 2017 ; Peng et al, 2018 ; Zheng et al, 2019 ). Unfortunately, some IBD patients with IL10RA deficiency fail to achieve successful engraftment after the UCBT,_ENREF_3 limiting the application of UCBT in IBD patients ( Zheng et al, 2019 ). However, the impact of defective IL10 signaling on human intestinal inflammation has not been clarified ( Glocker et al, 2009 ; Zheng et al, 2019 ) and little is known on risk factors associated with engraftment failure after the UCBT in IBD patients with IL10RA deficiency.…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, some IBD patients with IL10RA deficiency fail to achieve successful engraftment after the UCBT,_ENREF_3 limiting the application of UCBT in IBD patients ( Zheng et al, 2019 ). However, the impact of defective IL10 signaling on human intestinal inflammation has not been clarified ( Glocker et al, 2009 ; Zheng et al, 2019 ) and little is known on risk factors associated with engraftment failure after the UCBT in IBD patients with IL10RA deficiency.…”

Section: Introductionmentioning

confidence: 99%

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Fecal Microbial Signatures Are Associated With Engraftment Failure Following Umbilical Cord Blood Transplantation in Pediatric Crohn’s Disease Patients With IL10RA Deficiency

et al. 2020

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Objectives Umbilical cord blood transplantation (UCBT) is associated with a relatively high rate of engraftment failure. This study aimed at exploring whether any fecal microbiota could be associated with engraftment failure following UCBT in Crohn’s disease patients with IL10RA deficiency. Methods Thirteen patients were recruited and their 230 fecal samples were collected longitudinally from immediately before conditioning chemotherapy to 8 weeks post the UCBT. The V3-V4 regions of the bacterial 16S rRNA gene were amplified by PCR and sequenced, followed by bioinformatics analyses. Results Following the UCBT, 7 out of 13 patients achieved neutrophil and platelet engraftment with a median of 21 and 28 days, respectively (S group), while 6 patients failed to achieve engraftment (F group). In comparison with that in the S group, significantly lower Shannon diversity values on the UCBT day ( P = 0.0176) and less abundance of Bifidobacterium longum , Bifidobacterium pseudolongum , Enterobacteriaceae_538000 , and one taxon of Lachnospiraceae family was detected in the F group, accompanied by significantly higher abundances of four taxa including Lautropia , Pseudomonas , and species Microvirgula aerodenitrificans during the chemotherapy period as well as UCBT. The abundances of thirty OTUs were correlated significantly with clinical indices. Conclusions Microbial indicators of reduced diversity of microbiota and signatures of specific bacterial abundances, such as a lower abundance of Bifidobacterium longum , for engraftment failure would require validation. These indicators may help for the risk stratification in patients with IL10RA deficiency undergoing UCBT.

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Risk assessment and genetic counseling for hematologic malignancies—Practice resource of the National Society of Genetic Counselors

Stewart,

Helber,

Bannon

et al. 2024

Journal of Genetic Counseling

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Hematologic malignancies (HMs) are a heterogeneous group of cancers impacting individuals of all ages that have been increasingly recognized in association with various germline predisposition syndromes. Given the myriad of malignancy subtypes, expanding differential diagnoses, and unique sample selection requirements, evaluation for hereditary predisposition to HM presents both challenges as well as exciting opportunities in the ever‐evolving field of genetic counseling. This practice resource has been developed as a foundational resource for genetic counseling approaches to hereditary HMs and aims to empower genetic counselors who encounter individuals and families with HMs in their practice.

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Phenotypic Characterization of Very Early-Onset Inflammatory Bowel Disease with Interleukin-10 Signaling Deficiency: Based on a Large Cohort Study

Cited by 37 publications

References 40 publications

Phenotype of Very-Early-Onset Inflammatory Bowel Disease with Interleukin-10 Receptor A Mutations in 22 Chinese Children

Phenotype of Very-Early-Onset Inflammatory Bowel Disease with Interleukin-10 Receptor A Mutations in 22 Chinese Children

Fecal Microbial Signatures Are Associated With Engraftment Failure Following Umbilical Cord Blood Transplantation in Pediatric Crohn’s Disease Patients With IL10RA Deficiency

Risk assessment and genetic counseling for hematologic malignancies—Practice resource of the National Society of Genetic Counselors

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