IL10RB基因变异致极早发炎症性肠病临床表型及遗传学分析3例病例系列报告OA

Background While IL10RA gene variants are a common cause of very early-onset inflammatory bowel disease(VEO-IBD)in China,IL10RB gene variants are extremely rare,leading to a lack of clinical awareness.Objective To analyze the clinical and genetic characteristics in three children with VEO-IBD caused by IL10RB gene variations.Design Case series report.Methods The clinical features,laboratory and genetic test results,treatment,and outcomes of three children with IL10RB deficiency admitted to the Children's Hospital of Fudan University between May 2016 and August 2025 were summarized.Functional validation was performed using flow cytometry.Main Outcome Measures The patients'clinical phenotypic characteristics,treatment responses,genetic features,and in vitro functional validation results.Results All three patients presented with diarrhea as the primary initial symptom during the neonatal period.Throughout the disease course,all three patients experienced recurrent infections,malnutrition,perianal lesions,oral ulcers,and skin rashes.Based on endoscopic and histopathological findings,they were diagnosed with VEO-IBD.One case was complicated by pancreatic lymphoma.Genetic testing confirmed IL10RB mutations in all three patients,including two nonsense variants and one missense variant,all inherited from their parents.Due to severe intestinal involvement,all three patients underwent intestinal surgery.Two patients received allogeneic hematopoietic stem cell transplantation(HSCT),one of whom achieved long-term clinical remission after transplantation,while the other,who had pancreatic lymphoma,died of infection 10 days after transplantation.Functional validation via flow cytometry showed impaired STAT3 phosphorylation in peripheral blood mononuclear cells(PBMCs)after recombinant human IL-10 stimulation in the non-transplanted patient,whereas normal STAT3 phosphorylation was observed in the HSCT-treated patient.Conclusion Compared to VEO-IBD associated with IL10RA or IL10 gene variants,IL10RB mutation-related VEO-IBD is characterized by more severe intestinal involvement,a higher rate of surgical intervention,and an increased risk of lymphoma.Early HSCT is recommended for these patients once the diagnosis is confirmed.