D3.362 - Ulcerative Colitis Developing in an Immunodeficiency Patient with CD19 Gene Mutation: A Case Report

Introduction and Aim: Inborn errors of immunity (IEIs) are a group of diseases characterized not only by susceptibility to infection but also by signs of immune dysregulation such as autoimmunity and chronic inflammation. CD19, a key component of B cell receptor (BCR) signaling, plays a critical role in B cell activation, proliferation, and the enhancement of antibody responses. CD19 deficiency is a rare cause of humoral immunodeficiency, characterized by hypogammaglobulinemia, poor vaccine responses, and recurrent infections.

In recent years, it has been shown that B cells play a role not only in antibody production but also in regulatory B cell functions and modulation of T cell responses, suggesting that B cell defects can predispose to loss of immune tolerance and the development of inflammatory disease. Inflammatory bowel disease, particularly in monogenic IEIs, can have an early onset and atypical course. This case report aims to describe the coexistence of immunodeficiency and ulcerative colitis in a patient with a heterozygous variant in the CD19 gene.

Case: A 16.5-year-old girl presented to the Pediatric Immunology-Allergy outpatient clinic with a complaint of experiencing more than 8 upper respiratory tract infections per year for the past 3 years. The patient was scheduled for immunoglobulin G-A-M, total IgE, IgG subclasses, specific IgE inhaler panel, isohemagglutinin titer, complete blood count, and flow cytometry. The patient's test results were: IgG 561 mg/dl, IgA 41 mg/dl, IgM 140 mg/dl, Total IgE 672 IU/ml, IgG1 544 mg/dl, IgG2 159 mg/dl, IgG3 3 mg/dl, IgG4 24 mg/dl. Anti-B 1/4 was positive, CD3+ cells 83.64%, CD3+CD4+ cells 34.95%, CD3+CD8+ cells 47.69%, CD19 cells 8.75%, CD16+CD6+ cells 4.84%. Intravenous immunoglobulin (IVIG) replacement therapy was planned for the patient. Clinical exome sequencing genetic testing was also planned. The patient was found to be heterozygous for the intronic c.1199-15 T>C variant in the CD19 gene (NM_001770.6). The patient experienced severe headache and vomiting during IVIG treatment, prompting a change in preparation and premedication. Despite this, the patient continued to experience headache and vomiting, leading to the decision to initiate facilitated subcutaneous immunoglobulin (fSCIG) therapy. A patient who received SCIG therapy for 2 years experienced recurrent severe abdominal pain, so SCIG treatment was discontinued and IVIG therapy was planned. Due to persistent symptoms, a pediatric gastroenterology consultation was scheduled. Colonoscopy revealed a diagnosis of ulcerative colitis. The patient was started on infliximab and sulfasalazine treatment. After 9 months of treatment, the patient's gastrointestinal symptoms improved and were brought under control.

Conclusion: This case demonstrates that in patients with CD19 gene defects, not only infections but also gastrointestinal immune dysregulation may be part of the clinical spectrum; highlighting the critical role of B cells in intestinal immune homeostasis. Ulcerative colitis developing on the background of CD19 deficiency indicates that gastrointestinal symptoms should be carefully evaluated in patients with IEIs.