Pulmonary involvement with immunodeficiency: the role of CTLA-4 in the pathogenesis of granulomatous lymphocytic interstitial lung disease (GLILD) – an Italian case report

ABSTRACT
We present the case of a 14-year-old female patient who was referred to us in 2024 due to coughing, widespread dermatitis and frequent episodes of diarrhea.
Her medical history included atopic dermatitis in childhood. Initial blood tests and diagnostic tests revealed autoimmune hemolytic anemia, widespread lymphadenopathy and splenomegaly. Further diagnostic investigations revealed rounded pulmonary opacities on chest X-ray, so second-level diagnostic tests were performed, which revealed the presence of a mutation in the CTLA-4 gene on genetic analysis, suggesting a form of primary immunodeficiency, leading to a diagnosis of GLILD. Treatment initially involved corticosteroid therapy and the administration of intravenous immunoglobulins. The therapeutic breakthrough came with the introduction of biological therapy with Abatacept, a CTLA-4 signal modulator, which led to remission of the disease.

IMPACT STATEMENT
This case highlights the importance of differential diagnosis and multidisciplinary collaboration in the management of GLILD, offering a superior strategy compared to traditional corticosteroid-based management. Early adoption of targeted biological interventions is essential to halt disease progression, preventing the development of irreversible pulmonary fibrosis and reducing treatment-related morbidity, thereby improving long-term survival and quality of life for patients with CVID or CVID-like disorders.

KEY WORDS
Case report; GLILD; immunodeficiency.

Received: Mar 02, 2026
Accepted: Apr 22, 2026
Published: Sept 11, 2026