Clinical Features of <i>Interleukin 10 Receptor</i> Gene Mutations in Children With Very Early–Onset Inflammatory Bowel Disease

Beşer, Ömer Faruk; Conde, Cecilia Domínguez; Serwas, Nina K.; Çokuğraş, Fügen; Kutlu, Tufan; Boztuğ, Kaan; Erkan, Tülay

doi:10.1097/mpg.0000000000000621

Cited by 49 publications

(40 citation statements)

References 30 publications

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“…Treatment with the above agents usually results in no or only mild improvement of clinical manifestations. A few patients have had to undergo bowel resection and ileostomy or colostomy due to poor treatment efficacy and resistance to therapy [22]. Given the fact that IL-10 acts predominantly on hematopoietic and immune cells, allogeneic hematopoietic stem cell transplantation (HSCT) has been attempted as a curative therapy for VEO-IBD patients with IL-10 or IL-10R mutations [10, 13, 17, 19, 23, 25, 30].…”

Section: Clinical Features Of Il-10 or Il-10r Mutation-associated Veomentioning

confidence: 99%

IL-10 and IL-10 Receptor Mutations in Very Early Onset Inflammatory Bowel Disease

et al. 2017

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Very early onset inflammatory bowel disease (VEO-IBD) is a unique disease entity with a complex genetic susceptibility in affected patients. Next-generation gene sequencing techniques have revealed various monogenetic mutations contributing to the pathogenesis of VEO-IBD, including interleukin 10 (IL-10) and IL-10 receptor (IL-10R) mutations. In this article, we reviewed the features of and effective therapeutic options for VEO-IBD with IL-10 and/or IL-10R mutations. The IL-10 signal pathway inhibits the release of several key cytokines and thereby has a significant anti-inflammatory effect in the gastrointestinal tract. Mutations of the genes encoding IL-10 and/or IL-10R have been detected in VEO-IBD patients among myriad populations throughout the world. VEO-IBD patients with IL-10 or IL-10R mutations often present with repeated bouts of bloody diarrhea, marked weight loss, growth retardation, and recurrent perianal problems, including abscesses, fistulas, and significant fissures. Moreover, some patients may have folliculitis and present with pulmonary infections. While the therapeutic efficacy of immunosuppressants is typically poor in these patients, allogeneic hematopoietic stem cell transplantation (HSCT) has been reported to improve symptoms significantly. However, the long-term prognosis of VEO-IBD patients with IL-10 or IL-10R gene mutations treated with HSCT requires further exploration to verify the efficacy and safety of this treatment. We concluded that clinicians should recognize the clinical phenotype of VEO-IBD, as mutational analysis of the IL-10 pathway can support the diagnosis and prompt early treatment of this complicated disease.

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Section: Clinical Features Of Il-10 or Il-10r Mutation-associated Veomentioning

confidence: 99%

IL-10 and IL-10 Receptor Mutations in Very Early Onset Inflammatory Bowel Disease

et al. 2017

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“…22 cases have been reported in East Asia, of which 21 cases showed IL-10RA mutation with only 1 case showing IL-10RB mutation. This is a contrast to the European cases in which IL-10RA and IL-10RB mutations were almost equal [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27].…”

Section: Il-10 and Il-10r Mutations In Veo-ibdmentioning

confidence: 74%

“…Treatment with these drugs results in either no improvement or only a mild improvement of the clinical features. Due to poor efficacy of treatment and drug resistance, some patients have undergone bowel resection and ileostomy or colostomy [22]. As a matter of fact that IL-10 has a predominant action on the immune and hematopoetic cells, an attempt has been made to use Allogenic Hematopoetic Stem Cell Transplantation (HSCT) as a curative therapy for patients of VEO-IBD with mutations of IL-10/IL-10R [10,13,17,19,23,25,30].…”

Section: Clinical Presentation In Case Of Veo-ibd Associated With Il-mentioning

confidence: 99%

Interleukin 10/ Interleukin-10R Mutations Causing Very Early Onset Inflammatory Bowel Disease

Pasha¹,

Ekyolu²,

Hongmei³

2018

IJCRR

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A unique disease entity called Very early onset inflammatory bowel disease [VEO-IBD] in which the affected patients show a complex genetic susceptibility. Various monogenic mutations which contribute to the pathogenesis of VEO-IBD have been attributed by gene sequencing techniques, including mutations in Interleukin 10 (IL-10) and Interleukin 10 receptor (IL-10R). The IL-10 pathway has an inhibitory effect on the release of several cytokines and hence, has an anti-inflammatory effect on the gastrointestinal tract. Among the reported patients with VEO-IBD in the world literature, mutations in the genes encoding for IL-10 and IL-10R have been detected. These patients present with symptoms of bloody diarrhea, significant weight loss, growth retardation and recurrent perianal abscesses, fistulas and fissures. Some patients may also have respiratory infections and folliculitis. As the therapeutic efficacy of immunosuppressive drugs is poor in these patients, it has been reported that allogenic hematopoetic stem cell transplantation (HSCT) can improve the symptoms significantly. However, in order to verify the efficacy and safety of this treatment, and the long term prognosis of VEO-IBD patients with IL-10/IL-10R mutations , further study and exploration is yet requires. In this article, we would conclude the importance for physicians to recognize the clinical phenotype of VEO-IBD and a mutational analysis of the IL-10/IL-10R can help in confirming the diagnosis and start early and effective treatment of this disease.

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“…A number of genetic associations with perianal fistula in Crohn's disease have been identified. The IL‐10R mutation predicts an early onset and severe form of Crohn's disease with ubiquitous perianal disease . Some early onset, IBD‐like monogenic diseases include frequent or severe perianal disease such as glycogen storage disease type 1b with mutation in SLC37A4, leucocyte adhesion deficiency 1 (ITGB2) and X‐linked lymphoproliferative syndrome 2 (XIAP) .…”

Section: Methodsmentioning

confidence: 99%

“…The IL-10R mutation predicts an early onset and severe form of Crohn's disease with ubiquitous perianal disease. 19 Some early onset, IBD-like monogenic diseases include frequent or severe perianal disease such as glycogen storage disease type 1b with mutation in SLC37A4, leucocyte adhesion deficiency 1 (ITGB2) and X-linked lymphoproliferative syndrome 2 (XIAP). 20 In a recent study of IBD with onset before the age of 2, 60% (9 of 15) of patients with a Crohn's-like phenotype had perianal disease.…”

Section: Genetic Predispositionmentioning

confidence: 99%

Review article: pathogenesis of Crohn's perianal fistula—understanding factors impacting on success and failure of treatment strategies

Tozer

Lung

Lobo

et al. 2018

Aliment Pharmacol Ther

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Clinical Features of Interleukin 10 Receptor Gene Mutations in Children With Very Early–Onset Inflammatory Bowel Disease

Abstract: In spite of the small number of patients with mutations affecting the IL-10 signaling pathway in our study, in all of the patients with IL10 receptor mutations, the disease onset occurs at an early age, the prognosis is poor, and the response to treatment is insufficient.

Cited by 49 publications

References 30 publications

IL-10 and IL-10 Receptor Mutations in Very Early Onset Inflammatory Bowel Disease

IL-10 and IL-10 Receptor Mutations in Very Early Onset Inflammatory Bowel Disease

Interleukin 10/ Interleukin-10R Mutations Causing Very Early Onset Inflammatory Bowel Disease

Review article: pathogenesis of Crohn's perianal fistula—understanding factors impacting on success and failure of treatment strategies

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