Introduction: The CTLA-4 deficiency is characterized by immune dysregulation, which may present with autoimmunity, autoinflammation, immunodeficiency, and lymphoproliferation. Objective: to describe the clinical and immunological features of a patient with CTLA-4 deficiency diagnosed by microarrayCGH test.
Case Report: A 19 years old girl born of non-consanguineous parents without relevant family history, was admitted at age of 11 with autoimmune haemolytic anemia (AIHA), Coombs +. She was treated with corticosteroids with good outcome. She had a history of severe atopic dermatitis, recurrent infections (pneumonias, otitis, herpes zoster), development delay and malformations (bilateral clubfoot, scoliosis).
The Immunological assessment revealed lymphopenia, partial IgA deficiency and elevated IgE. Ly: 1050/mm3 T-cells: 33% (346/mm3) CD3+CD4+: 20% (210/mm3) CD3+CD8+: 9% B-cells: 60% NK-cells: 6% IgG7,39g/dl IgA0.65g/dl IgM2,11g/dl IgE696UI/ml. Good response to polysaccharide antigens but impaired to proteins. The %Th17-cells was normal.
She was put on trimethoprim-sulfametoxasol and referred to a geneticist with suspected immunodeficiency associated with genetic syndrome. Cytogenetic analysis on peripheral blood cells showed multiple chromosome rearrangements: 46,XX,t(1;13)(p13;q33),der(2)t(2;14)(q33;q13),der(3)t(3;6)(p24;q23),der(6)t(3;6)(p25;q23),der(6)t(2;6)(q33;p21),der(14)t(6;14)(p21;q13),inv(9)(p12q13)[20] karyotype. The microarray CGH test detected multiple deletions: deletion 13q33.1->33.2 of 4.62 Mb; deletion 3p24.1 of 997 Kb; deletion 2q33.2->33.3 of 554 Kb; and gain of 332 Kb, Xp22.31. The deletion in chromosome 2 involves CTLA4 and ICOS genes.CTLA-4 protein showed diminished expression in patient´s Tregs cells compared to control (11% vs 45%). cTHf were increased (30%) while switched memory B cells were low.
After diagnosis, she presented 3 events of AIHA treated with corticosteroids and mycophenolate. After 2 years she developed pancytopenia. Abatacept was initiated with good tolerance and outcome. Discussion: we present a patient with a complex phenotype associated to severe autoimmunity, in whom the diagnosis of CTLA-4 deficiency by microarrayCGH test plus flow cytometry, allowed a correct therapeutic approach. The interdisciplinary work with the participation of geneticists was the key to arrive diagnosis.