A study on the interleukin-10 receptor gene mutations and neonatal very early onset inflammatory bowel disease in 5 infants

Abstract

Objective To study the clinical features, diagnosis and treatment of neonatal very early onset inflammatory bowel disease(VEO-IBD) to improve the diagnosis and treatment of the disease. Method From Jan 2013 to Dec 2015, five infants with VEO-IBD admitted to Peking University First Hospital were reviewed and analyzed. Their clinical data included general condition, clinical symptoms, laboratory tests, autoimmune antibodies (ANCA, dsDNA, ANA and ENA), colonoscopy, pathological results and therapeutic response. Interleukin-10 receptor A (IL-10RA) gene was examined in all patients. All the patients were followed up for more than 1 year. Result Three of the five patients had a family history. Persistent diarrhea was the most common presenting symptom. One of them received surgery because of intestinal necrosis and developed typical symptoms of IBD half a year later. Bloody stool or positive fecal occult blood test were found in all infants. Fever, anemia, oral ulcer, perianal lesions and malnutrition were common concomitant symptoms. Most of the patients had elevated WBC, CRP and ESR, and 4 of them had positive autoimmune antibodies. Colonoscopy showed multiple ulcers affecting the colon. Intestinal biopsies revealed acute and chronic inflammation. 4 of patients were found to have cryptitis and crypt abscesses.Gene sequencing revealed IL-10RA gene mutation in all five patients, including 1 case with homozygous mutation and 4 heterozygous mutations. 4 patients received steroid and mesalazine therapy and only 1 patient′s symptoms were controlled. However, the colonoscopy result was still abnormal in this patient.4 patients had poor response to further infliximab and (or) thalidomide therapy. 1 of them received surgery because of intestinal obstruction at 2-year-old. Conclusion Neonatal VEO-IBD was associated with IL-10RA gene mutation. The patients had severe symptoms and poor response to conventional medications. The effects of biological agents and thalidomide were still not sure. Key words: Interleukin-10 receptor alpha subunit; Genetic testing; Early onset inflammatory bowel disease; Infant, newborn