D1.334 - A Novel Variant in ALPS Type V Due to CTLA-4 Deficiency: A Case Presenting with Cytopenia
Case report
Introduction
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T-cell-mediated immune responses and is associated with autosomal dominant immune dysregulation syndromes. Clinical features include recurrent infections, autoimmunity, hypogammaglobulinemia, and splenomegaly. Here, we present a patient who was admitted with cytopenia and was found to have a previously unreported variant in the CTLA-4 gene.
Case Report
A 10-year-old girl presented with widespread bruising. Physical examination revealed splenomegaly and ecchymosis. Laboratory findings were as follows: leukocyte count 2,690/mm³, neutrophil count 850/mm³, lymphocyte count 970/mm³, platelet count 4,000/mm³, and hemoglobin 10.8 g/dL. Reticulocytosis and direct Coombs positivity were observed. Viral serology was negative, and bone marrow examination showed no signs of malignancy. Immunoglobulin levels were: IgG 1,642 mg/dL (reference: 935-1,175 mg/dL), IgA 209 mg/dL (94-137 mg/dL), and IgM 137 mg/dL (96-129 mg/dL). Intravenous immunoglobulin and steroids were initiated for autoimmune hemolytic anemia and immune thrombocytopenic purpura.
Despite four months of steroid treatment, hemolysis persisted, prompting the initiation of rituximab. Two months after rituximab therapy, laboratory results were as follows: leukocyte count 2,730/mm³, neutrophil count 550/mm³, lymphocyte count 930/mm³, platelet count 333,000/mm³, hemoglobin 12.1 g/dL, IgG 528 mg/dL, IgA 57 mg/dL, and IgM 31 mg/dL. Trimethoprim-sulfamethoxazole prophylaxis was started but discontinued due to a hypersensitivity reaction.
Due to Evans syndrome and splenomegaly, autoimmune lymphoproliferative syndrome (ALPS) was suspected. However, lymphocyte subset analysis revealed normal double-negative T cells. Whole exome sequencing was performed to investigate ALPS-like diseases, revealing a heterozygous CTLA-4 c.509T>A (p.Val170Asp) variant. Flow cytometry showed reduced CTLA-4 expression compared to healthy controls. This variant has not been previously reported in the literature, and family segregation analysis is ongoing.
Conclusion
This case highlights the broad clinical spectrum of immune dysregulation due to CTLA-4 deficiency.
