Details

Autor(en) / Beteiligte

• Gámez-Díaz, Laura, MSc
• August, Dietrich, cand. MD
• Stepensky, Polina, MD
• Revel-Vilk, Shoshana, MD, MSc
• Seidel, Markus G., MD
• Noriko, Mitsuiki, MD
• Morio, Tomohiro, MD, PhD
• Worth, Austen J.J., MD, PhD
• Blessing, Jacob, MD, PhD
• Van de Veerdonk, Frank, MD, PhD
• Feuchtinger, Tobias, MD
• Kanariou, Maria, MD, PhD
• Schmitt-Graeff, Annette, MD
• Jung, Sophie, DD, PhD
• Seneviratne, Suranjith, MD, PhD
• Burns, Siobhan, MD
• Belohradsky, Bernd H., MD
• Rezaei, Nima, MD, PhD
• Bakhtiar, Shahrzad, MD
• Speckmann, Carsten, MD
• Jordan, Michael, MD
• Grimbacher, Bodo, MD

Titel

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

Ist Teil von

• Journal of allergy and clinical immunology, 2016-01, Vol.137 (1), p.223-230

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.