Efficacy of abatacept treatment in a patient with enteropathy carrying a variant of unsignificance in CTLA4 gene: A case report

Abstract

BACKGROUND

Cytotoxic T Lymphocyte Antigen-4 (CTLA4) deficiency is a genetic defect that causes a common variable immunodeficiency (CVID) clinical phenotype. Several studies have reported an association between CTLA mutations or variants and various autoimmune diseases. Targeted therapy models, which have become increasingly popular in recent years, have been successful in treating CTLA4 deficiency. In this article, we discuss the clinical outcomes of abatacept treatment in a patient with CTLA4 and lipopolysaccharide-responsive beige-like anchor (LRBA) variants that was previously diagnosed with CVID.

CASE SUMMARY

A 25-year-old female patient, who was visibly cachectic, visited our clinic over the course of five years, complaining of diarrhea. The patient was diagnosed with ulcerative colitis in the centers she had visited previously, and various treatments were administered; however, clinical improvement could not be achieved. Severe hypokalemia was detected during an examination. Her serum immunoglobulin levels, CD19⁺ B-cell percentage, and CD4/CD8 ratio were low. An endoscopic examination revealed erosive gastritis, nodular duodenitis, and pancolitis. Histopathological findings supported the presence of immune mediated enteropathy. When the patient was examined carefully, she was diagnosed with CVID, and intravenous immunoglobulin treatment was initiated. Peroral and rectal therapeutic drugs including steroid therapy episodes were administered to treat the immune mediated enteropathy. Strict follow-ups and treatment were performed due to the hypokalemia. After conducting genetic analyses, the CTLA4 and LRBA variants were identified and abatacept treatment was initiated. With targeted therapy, the patient’s clinical and laboratory findings rapidly regressed, and there was an increase in weight.

CONCLUSION

The heterozygous CTLA4 variant identified in the patient has been previously shown to be associated with various autoimmune diseases. The successful clinical outcome of abatacept treatment in this patient supports the idea that this variant plays a role in the immunopathogenesis of the disease. In the presence of severe disease, abatacept therapy should be considered until further testing can be conducted.

Keywords: Common variable immunodeficiency, Abatacept, CTLA4 antigen, Case report

Core Tip: In this article, a 25-year-old female patient who applied to our outpatient clinic with the complaints of severe diarrhea and weight loss is presented. As a result of the clinical examination, laboratory tests and histopathological examinations, the patient was diagnosed with common variable immunodeficiency with severe enteropathy. Variants of uncertain significance were detected in 1 cytotoxic T lymphocyte antigen-4 (CTLA4) gene region and 2 lipopolysaccharide-responsive beige-like anchor gene regions in the patient who underwent Whole Exome Sequencing test. Although these polymorphisms have been listed as non-pathogenic in the variant database, their association with some autoimmune diseases had been shown in the literature before. CTLA-4-Ig fusion protein, which had been shown to be effective in these autoimmune diseases, was administered to our patient without delay and a dramatic improvement was achieved in clinical findings.