Early Diagnosis and Hematopoietic Stem Cell Transplantation for IL10R Deficiency Leading to Very Early-Onset Inflammatory Bowel Disease Are Essential in Familial Cases.

Neslihan Edeer Karaca,Nesrin Gulez,Serap Aksoylar,Sanem Akarcan,Kaan Boztug,Necil Kutukculer,Ferah Genel,Ezgi Ulusoy,Guzide Aksu,Savas Kansoy,Tatjana Hirschmugl,Salih Gozmen

doi:10.1155/2016/5459029

Abstract

Alterations of immune homeostasis in the gut may result in development of inflammatory bowel disease. A five-month-old girl was referred for recurrent respiratory and genitourinary tract infections, sepsis in neonatal period, chronic diarrhea, perianal abscess, rectovaginal fistula, and hyperemic skin lesions. She was born to second-degree consanguineous, healthy parents. Her elder siblings were lost at 4 months of age due to sepsis and 1 year of age due to inflammatory bowel disease, respectively. Absolute neutrophil and lymphocyte counts, immunoglobulin levels, and lymphocyte subsets were normal ruling out severe congenital neutropenia and classic severe combined immunodeficiencies. Quantitative determination of oxidative burst was normal, excluding chronic granulomatous disease. Colonoscopy revealed granulation, ulceration, and pseudopolyps, compatible with colitis. Very early-onset colitis and perianal disease leading to fistula formation suggested probability of inherited deficiencies of IL-10 or IL-10 receptor. A mutation at position c.G477A in exon of the IL10RB gene, resulting in a stop codon at position p.W159X, was identified. The patient underwent myeloablative hematopoietic stem cell transplantation from full matched father at 11 months of age. Perianal lesions, chronic diarrhea, and recurrent infections resolved after transplantation. IL-10/IL-10R deficiencies must be considered in patients with early-onset enterocolitis.

Highlights

Inflammatory bowel diseases (IBD) are complex, mostly polygenic disorders characterized by relapsing intestinal inflammation
Multiple genetic defects in genes such as IL10, interleukin-10 receptor (IL-10R), TTC7A, FOXP3, PLCG2, LRBA, G6PC3, IKBKG, and CYBB are associated with IBD [3,4,5]
Deficiencies of interleukin-10 (IL-10) and IL-10 receptor (IL10R), leading to defective STAT3 dimerization, have been shown to cause severe dysregulation of the immune system, resulting in VEO-IBD with perianal disease and the key to an effective therapy lies in early diagnosis and successful hematopoietic stem cell transplantation (HSCT) in these patients [2, 5]

Summary

Introduction

Inflammatory bowel diseases (IBD) are complex, mostly polygenic disorders characterized by relapsing intestinal inflammation. Earlyonset IBD (before 5 years) and very early-onset IBD (VEOIBD, before 2 years) usually have severe and therapy-resistant courses, and the majority of VEO-IBD are caused by monogenic defects [2]. Interleukin-10 is an important anti-inflammatory cytokine in humans. Deficiencies of interleukin-10 (IL-10) and IL-10 receptor (IL10R), leading to defective STAT3 dimerization, have been shown to cause severe dysregulation of the immune system, resulting in VEO-IBD with perianal disease and the key to an effective therapy lies in early diagnosis and successful hematopoietic stem cell transplantation (HSCT) in these patients [2, 5]. A Turkish IL10RB deficient patient with a positive family history of early-onset enterocolitis cured with HSCT is presented

Case Presentation

Findings

Discussion