Clinical Phenotypes and Immunological Characteristics of 18 Egyptian LRBA Deficiency Patients
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ORIGINAL ARTICLE
Clinical Phenotypes and Immunological Characteristics of 18 Egyptian LRBA Deficiency Patients Safa Meshaal 1 & Rabab El Hawary 1 & Rana Adel 1 & Dalia Abd Elaziz 2 & Aya Erfan 1 & Sohilla Lotfy 2 & Mona Hafez 2 & Mona Hassan 2 & Matthew Johnson 3 & Jessica Rojas-Restrepo 4 & Laura Gamez-Diaz 4 & Bodo Grimbacher 4,5,6,7 & Walaa Shoman 8 & Yasmine Abdelmeguid 8 & Jeannette Boutros 2 & Nermeen Galal 2 & Nancy El-Guindy 1 & Aisha Elmarsafy 2 Received: 2 January 2020 / Accepted: 28 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords LRBA . autoimmunity . CTLA4 . immune dysregulation . T regulatory cells
Safa Meshaal and Rabab El Hawary contributed equally to this work. Nancy El-Guindy and Aisha Elmarsafy are equal senior co-authorship * Safa Meshaal [email protected]; [email protected] 1
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Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CC), Medical Center, Faculty of Medicine, Albert-Ludwig-University of Freiburg, Freiburg, Germany
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DZIF – German Center for Infection Research, Satellite Center Freiburg, Germany, Freiburg, Germany
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CIBSS – Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University,
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