Clinical, immunologic, molecular analyses and outcomes of iranian patients with LRBA deficiency: A longitudinal study.

Background: LPS-responsive beige-like anchor protein (LRBA) deficiency is a combined immunodeficiency caused by mutation in LRBA gene. The patients have a variety of clinical symptoms including hypogammaglobulinemia, recurrent infections, autoimmunity, and enteropathy.

Methods: A total of 17 LRBA-deficient patients were enrolled in this longitudinal study. For all patients, demographic information, clinical records, laboratory, and molecular data were collected. Result: Hypogammaglobulinemia was reported in 14 (82.4%), CD4+ T-cell deficiency in five (29.4%), NK cell deficiency in three (21.4%), and CD19+ B-cell deficiency in 11 (64.7%) patients. All patients had history of infectious complications; pneumonia was the most common (76.5%) occurring infection. A history of lymphoproliferative disorders was observed in 14 (82.3%), enteropathy in 13 (76.5%), allergic symptoms in six (35.5%), neurologic problems in four (23.5), and autoimmunity (mostly autoimmune cytopenia) in 13 (76.5%) patients. Sirolimus treatment improved enteropathy of patients with remarkable success. The 20-year overall survival rate declined to 70.6%.

Conclusion: LRBA deficiency has a very broad and variable phenotype and should be considered, especially in children with early-onset hypogammaglobulinemia, severe autoimmune manifestations, enteropathy, lymphoproliferation, and recurrent respiratory tract infections.