Clinical Phenotypes and Immunological Characteristics of 18 Egyptian LRBA Deficiency Patients


LPS-responsive beige-like anchor (LRBA) deficiency is an autosomal recessive primary immunodeficiency disorder, OMIM (#614700). LRBA deficiency patients suffer from variable manifestations including recurrent infections, immune dysregulation, autoimmunity, cytopenias, and enteropathy. This study describes different clinical phenotypes and immunological characteristics of 18 LRBA deficiency patients diagnosed from Egypt. T and B lymphocyte subpopulations, LRBA, and cytotoxic T lymphocyte-associated protein 4 (CTLA4) expression were evaluated in resting and stimulated T cells using flow cytometry. Next-generation sequencing was used to identify mutations in the LRBA gene. LRBA deficiency patients had significantly lower B cells and increased percentage of memory T cells. CTLA4 levels were lower in LRBA-deficient T regulatory cells in comparison to healthy donors at resting conditions and significantly increased upon stimulation of T cells. We identified 11 novel mutations in LRBA gene ranging from large deletions to point mutations. Finally, we were able to differentiate LRBA-deficient patients from healthy control and common variable immunodeficiency patients using a simple flow cytometry test performed on whole blood and without need to prior stimulation. LRBA deficiency has heterogeneous phenotypes with poor phenotype-genotype correlation since the same mutation may manifest differently even within the same family. Low LRBA expression, low numbers of B cells, increased numbers of memory T cells, and defective CTLA4 expression (which increase to normal level upon T cell stimulation) are useful laboratory tests to establish the diagnosis of LRBA deficiency. Screening of the siblings of affected patients is very important as patients may be asymptomatic at the beginning of the disease course.

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LPS-responsive beige-like anchor


Primary immunodeficiency


beige and Chediak-Higashi syndrome


cytotoxic T lymphocyte-associated protein 4


Autoimmune lymphoproliferative syndrome


inflammatory bowel disease


Common variable immunodeficiency


European society for immunodeficiency


Immune dysregulation, polyendocrinopathy, enteropathy, X-linked


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The authors thank Drs Raif Geha and Janet Chua of the Immunology Division Children’s Hospital, Harvard Medical School, Boston, MA, USA, for sequencing eight of the patients reported in the study.

The authors thank the Jeffrey Modell Foundation for providing genetic sequencing services for patients 10 and 11 through their genetic sequencing pilot program.

For genetic diagnosis of patients 13 and 14: BG receives support through the Deutsche Forschungsgemeinschaft (DFG) under Germany’s Excellence Strategy (CIBSS – EXC-2189 – Project ID 390939984, and RESIST – EXC 2155 – Project ID 39087428); through the E-rare program of the EU, managed by the DFG, grant code GR1617/14-1/iPAD; and through the “Netzwerke Seltener Erkrankungen” of the German Ministry of Education and Research (BMBF), grant code: GAIN_ 01GM1910A.


Genetic sequencing for four patients was supported by the Jeffrey Modell Foundation through their genetic sequencing pilot program and through the Deutsche Forschungsgemeinschaft (DFG) under Germany’s Excellence Strategy (CIBSS – EXC-2189 – Project ID 390939984, and RESIST – EXC 2155 – Project ID 39087428); through the E-rare program of the EU, managed by the DFG, grant code GR1617/14-1/iPAD; and through the “Netzwerke Seltener Erkrankungen” of the German Ministry of Education and Research (BMBF), grant code: GAIN_ 01GM1910A received by BG.

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Correspondence to Safa Meshaal.

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Nancy El-Guindy and Aisha Elmarsafy are equal senior co-authorship

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Meshaal, S., El Hawary, R., Adel, R. et al. Clinical Phenotypes and Immunological Characteristics of 18 Egyptian LRBA Deficiency Patients. J Clin Immunol 40, 820–832 (2020).

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  • LRBA
  • autoimmunity
  • CTLA4
  • immune dysregulation
  • T regulatory cells