Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency causes a variety of immune abnormalities due to decreased expression of CTLA-4. Various immunosuppressive agents, including prednisolone (PSL), have been used to treat its clinical manifestations; however, their efficacy is often insufficient, and their adverse effects are problematic. Abatacept, which modulates excessive immune responses via CTLA-4–mediated mechanisms, has been reported to be effective.
Splenomegaly was noted at a routine health checkup at 3 years of age, and the patient was subsequently referred to our hospital due to thrombocytopenia. She was diagnosed with immune thrombocytopenic purpura and recovered following intravenous immunoglobulin (IVIG) therapy. At 4 years and 1 month of age, she developed autoimmune hemolytic anemia. At 4 years and 2 months, she presented with right esotropia and loss of speech; brain MRI revealed inflammatory changes in the brainstem. After methylprednisolone (mPSL) pulse therapy, oral PSL was initiated. At 5 years of age, obesity due to long-term PSL use was observed, and mycophenolate mofetil was started to facilitate PSL tapering. At 6 years, hypogammaglobulinemia (309 mg/dL, below −2 SD of the age-matched reference) was detected, and regular prophylactic IVIG replacement therapy was initiated. PSL was successfully discontinued at 7 years of age. At 9 years, bilateral organizing pneumonia developed, necessitating reinitiation of PSL. Subsequent flow cytometric analysis of peripheral blood mononuclear cells revealed decreased CTLA-4 expression, and genetic testing suggested LRBA deficiency. At 14 years and 3 months, she developed right-sided hearing loss, otalgia, and rotational vertigo; brain MRI demonstrated multiple central nervous system lesions. mPSL pulse therapy and increased PSL dosing were required, resulting in marked deterioration of quality of life due to central obesity and osteoporosis. At 14 years and 5 months, abatacept was initiated, and PSL was gradually tapered and discontinued by 15 years and 9 months. Genetic testing later confirmed compound heterozygous LRBA deficiency. One year after discontinuation of PSL, she remains free of symptoms except for hypogammaglobulinemia, and her quality of life has improved.
Abatacept has been reported to have therapeutic efficacy in LRBA deficiency comparable to hematopoietic stem cell transplantation; however, the long-term efficacy and safety of abatacept remain unclear. Meanwhile, the role of hematopoietic stem cell transplantation has not yet been fully established. In this case, we plan to continue abatacept as long as disease control is maintained.
