The Extended Phenotype of Lps-Responsive Beige-Like Anchor Protein (Lrba) Deficiency Publisher Pubmed



Gamezdiaz L¹ ; August D¹ ; Stepensky P³ ; Revelvilk S³ ; Seidel MG⁴ ; Noriko M⁵ ; Morio T⁵ ; Worth AJJ⁶ ; Blessing J⁷ ; Van De Veerdonk F⁸ ; Feuchtinger T⁹ ; Kanariou M¹⁰ ; Schmittgraeff A¹¹ ; Jung S¹ Show All Authors Show Affiliations
Source: Journal of Allergy and Clinical Immunology Published:2016

Abstract

Background LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency caused by biallelic mutations in LRBA that abolish LRBA protein expression. Objective We sought to report the extended phenotype of LRBA deficiency in a cohort of 22 LRBA-deficient patients. Methods Clinical criteria, protein detection, and genetic sequencing were applied to diagnose LRBA deficiency. Results Ninety-three patients met the inclusion criteria and were considered to have possible LRBA deficiency. Twenty-four patients did not express LRBA protein and were labeled as having probable LRBA deficiency, whereas 22 were genetically confirmed as having definitive LRBA deficiency, with biallelic mutations in LRBA. Seventeen of these were novel and included homozygous or compound heterozygous mutations. Immune dysregulation (95%), organomegaly (86%), recurrent infections (71%), and hypogammaglobulinemia (57%) were the main clinical complications observed in LRBA-deficient patients. Although 81% of LRBA-deficient patients had normal T-cell counts, 73% had reduced regulatory T (Treg) cell numbers. Most LRBA-deficient patients had low B-cell subset counts, mainly in switched memory B cells (80%) and plasmablasts (92%), with a defective specific antibody response in 67%. Of the 22 patients, 3 are deceased, 2 were treated successfully with hematopoietic stem cell transplantation, 7 are receiving immunoglobulin replacement, and 15 are receiving immunosuppressive treatment with systemic corticosteroids alone or in combination with steroid-sparing agents. Conclusion This report describes the largest cohort of patients with LRBA deficiency and offers guidelines for physicians to identify LRBA deficiency, supporting appropriate clinical management. © 2015 American Academy of Allergy, Asthma & Immunology.