[Autoimmunity in Patients with CTLA-4 Haploinsufficiency]

CTLA4 deficiency is a disorder caused by mutations in the CTLA4 gene. T (TL) and B (BL) lymphocyte activity is affected, generating complex autoimmune dysregulation and immunodeficiency syndromes with variable clinical spectrum and diagnostic difficulty.

Clinical Presentation: A 16-year-old male with no significant family history presented with autoimmune hemolytic anemia, thrombocytopenia, episodes of diarrhea, atopic dermatitis, respiratory tract infections, rhinosinusitis, and recurrent otitis media, with multiple antibiotic therapies. Laboratory tests indicated immunoglobulin replacement and prophylactic antibiotic therapy with improvement. He continued to experience intermittent diarrhea and skin lesions. Biopsies ruled out infectious etiologies, and the patient was diagnosed with lichen planus, nummular eczema, and enteropathy associated with immunodeficiency. Treatment with immunosuppressants was initiated. Genetic testing diagnosed heterozygous CTLA4 deficiency. Laboratory results: IgA 1 mg, IgG 356 mg, IgM 2 mg, Leukocytes 9700/mm3, Neutrophils 8179/mm3, Monocytes 442/mm3, Lymphocytes 1055/mm3, LT 86.12% 909/mm3, LB 0.85% 9/mm3, NK cells 14.75% 156/mm3, LTCD4+ 60.82% 553/mm3, LTCD8+ 35.44% 322/mm3, isotype-switched memory LB 0%, non-isotype-switched memory LB 1.83%, CD21low LB 30.94%, LTnaive 8.84%, LTLmemory 82.66%.

The diagnosis of this pathology is difficult due to its wide clinical presentation. Impaired LT and LB function leads to severe autoimmune processes and progressive hypogammaglobulinemia, recurrent infections, and malignancies. Immunoglobulin, prophylactic antibiotics, immunosuppressants, and bone marrow transplantation are the mainstays of treatment. Recognizing this genetic defect allows for targeted treatment (abatacept) that will improve the quality of life and prognosis of patients.