Multisystem Autoimmune Inflammatory Disease, Including Colitis, Due to Inborn Error of Immunity.

Our understanding of inflammatory bowel disease is changing as we identify genetic variants associated with immune dysregulation. Inflammatory bowel disease undetermined, even when diagnosed in older children and adolescents, in the setting of multiple inflammatory and infectious diseases should raise the suspicion of complex immune dysregulation with a monogenic basis. We report a case of inflammatory bowel disease undetermined triggered by exposure to a nonsteroidal antiinflammatory drug in a 16-year-old girl with a background history of juvenile idiopathic arthritis, cytopenias, recurrent respiratory tract and middle ear infections, and esophageal candidiasis. Immunologic assessment included measurement of immunoglobulin levels, lymphocyte immunophenotyping, B-cell functional tests, and whole-exome sequencing. Laboratory investigation revealed defects of humoral immunity, including mild persistent hypogammaglobulinemia affecting all 3 isotypes and absent isohemagglutinins. Whole exome sequencing revealed a heterozygous TNFRSF13B (Tumor Necrosis Factor Receptor Superfamily Member 13B, or Transmembrane Activator and Calcium-modulating cyclophilin ligand Interactor, TACI) gene variant, which is associated with common variable immunodeficiency and the development of autoimmune diseases. In conclusion, a clinical history of recurrent infections, atypical histologic features of inflammatory bowel disease, additional autoimmune manifestations, and an inadequate response to conventional therapy should prompt the physician to refer to an immunologist with the query of inborn error of immunity. We report how extensive immune evaluation and genetic diagnosis can individualize care and facilitate a multidisciplinary team approach.

随着我们识别出与免疫失调相关的基因变异，我们对炎症性肠病的认识正在发生变化。即使在大龄儿童和青少年中诊断出的未定型炎症性肠病，在存在多种炎症和感染性疾病的情况下，也应怀疑存在单基因基础的复杂免疫失调。我们报告了一例16岁女孩的病例，该女孩有幼年特发性关节炎、血细胞减少、反复呼吸道和中耳感染以及食管念珠菌病病史，在使用非甾体抗炎药后引发了未定型炎症性肠病。免疫学评估包括免疫球蛋白水平测定、淋巴细胞免疫表型分析、B细胞功能检测以及全外显子组测序。实验室检查显示体液免疫存在缺陷，包括影响所有3种同种型的轻度持续性低丙种球蛋白血症以及血型同种凝集素缺失。全外显子组测序显示TNFRSF13B（肿瘤坏死因子受体超家族成员13B，或跨膜激活剂和钙调亲环素配体相互作用分子，TACI）基因存在杂合变异，该变异与常见变异型免疫缺陷以及自身免疫性疾病的发生有关。总之，反复感染的临床病史、炎症性肠病的非典型组织学特征、其他自身免疫表现以及对常规治疗反应不佳，应促使医生咨询免疫学家，考虑是否存在先天性免疫缺陷。我们报告了广泛的免疫评估和基因诊断如何能够实现个体化治疗并促进多学科团队协作。