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J Allergy Clin Immunol. 2016 Jan;137(1):223-230. doi: 10.1016/j.jaci.2015.09.025.

The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency.

Author information

1
Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany.
2
Pediatric Hematology-Oncology and Bone Marrow Transplantation, Hadassah Hebrew University Hospital, Jerusalem, Israel.
3
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology-Oncology, Medical University Graz, Graz, Austria.
4
Department of Pediatrics and Developmental Biology Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University, Tokyo, Japan.
5
Department of Immunology, Great Ormond Street Hospital for Children, London, United Kingdom.
6
Cincinnati Children's Hospital Medical Center, University of Cincinnati Medical School, Cincinnati, Ohio.
7
Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
8
Pediatric Hematology, Oncology and Stem Cell Transplantation, Dr. von Hauner University Children's Hospital, Ludwig-Maximilians-Universität, Munich, Germany.
9
Department of Immunology, "Aghia Sophia" Children's Hospital, Athens, Greece.
10
Department of Pathology, University Hospital Freiburg, Freiburg, Germany.
11
UCL Centre for Immunodeficiency, Royal Free Hospital Foundation Trust, London, United Kingdom.
12
Division of Immunology and Infectious Disease, University Childrens Hospital Munich, Munich, Germany.
13
Research Center for Immunodeficiencies, Children's Medical Center, and the Department of Immunology, School of Medicine Tehran University of Medical Sciences, Tehran, Iran.
14
Division for Stem Cell Transplantation and Immunology, Department for Children and Adolescents Medicine, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany.
15
Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany; Center for Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany.
16
Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany; UCL Centre for Immunodeficiency, Royal Free Hospital Foundation Trust, London, United Kingdom. Electronic address: bodo.grimbacher@uniklinik-freiburg.de.

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.

KEYWORDS:

LPS-responsive beige-like anchor protein; autoimmunity; common variable Immunodeficiency; enteropathy; hypogammaglobulinemia; lymphoproliferation; primary immunodeficiency

PMID:
26768763
DOI:
10.1016/j.jaci.2015.09.025
[Indexed for MEDLINE]

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