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Disorders of CTLA-4 expression, how they lead to CVID and dysregulated immune responses

Sun, Di; Heimall, Jennifer

Current Opinion in Allergy and Clinical Immunology: December 2019 - Volume 19 - Issue 6 - p 578–585
doi: 10.1097/ACI.0000000000000590
PRIMARY IMMUNE DEFICIENCY DISEASE: Edited by Stephen Jolles and M. Teresa (Maite) de la Morena

Purpose of review The landscape of common variable immunodeficiency disorder (CVID) is rapidly evolving as the availability of next-generation sequencing leads to the discovery of new monogenic causes with the clinical phenotype of CVID. Herein, the biology of cytotoxic T lymphocyte-associated protein four (CTLA-4), differentially expressed in FDCP6 homolog (DEF6), and lipopolysaccharide responsive beige-like anchor protein (LRBA), and their impact on the development of a dysregulated, rather than an isolated, infectious phenotype of CVID are explored.

Recent findings The broad clinical phenotype associated with these monogenic forms of CVID is described, and common approaches to treatment are reviewed.

Summary Knowledge of the biology, clinical manifestations, and treatment options trialed thus far in patients with CTLA-4 insufficiency, DEF6 deficiency, and LRBA deficiency are essential in the consideration and effective management of patients with CVID stemming from these monogenic causes.

Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

Correspondence to Jennifer Heimall, MD, Children's Hospital of Philadelphia, Division of Allergy and Immunology, Wood 3301, 3401 Civic Center Blvd, Philadelphia, PA 19104, USA. Tel: +1 215 590 2549; e-mail:

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