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LRBA Deficiency

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Humoral Primary Immunodeficiencies

Part of the book series: Rare Diseases of the Immune System ((RDIS))

Abstract

LRBA deficiency is an early-onset primary immunodeficiency (PID) caused by biallelic mutations in LRBA that abolish its protein expression. Clinically, LRBA deficiency presents with a broad clinical phenotype including immune dysregulation, recurrent infections, and hypogammaglobulinemia, accompanied by reduced expression of CTLA-4 as well as diminished numbers of regulatory T cells (Tregs), switched memory B cells, and plasmablasts. Currently, the diagnosis of LRBA deficiency is based on genome sequencing approaches, but screening diagnostic methods based on protein detection have also been implemented. LRBA-deficient patients frequently receive immune suppressive-based therapy and immunoglobulin replacement, since the implementation of HSCT as potential curative treatment for LRBA deficiency is still under debate. LRBA plays an essential role in the expression, function, and trafficking of CTLA-4 in Tregs, thereby controlling proinflammatory responses. However, the exact function of LRBA in other immune cells is not yet fully understood. Interestingly, LRBA-deficient mouse models do not mirror the human LRBA deficiency, as Lrba null mice do not present any clinical or immunological signs of disease and do not develop overt autoimmunity despite low levels of CTLA-4, reduced frequency of IL-10-producing B cells, and increased numbers of T follicular helper cells. In addition, Lrba null mice present normal B and T lymphocyte development and normal humoral response against T-dependent as well as T-independent antigens. Further analyses that elucidate the pathomechanisms of LRBA deficiency are needed in order to develop targeted therapies which improve the survival and quality life of LRBA-deficient patients.

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Authors and Affiliations

  1. Center for Chronic Immunodeficiency, University Medical Center of Freiburg, University of Freiburg, Freiburg im Breisgau, Germany

    Laura Gámez-Díaz

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  1. Laura Gámez-Díaz
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Correspondence to Laura Gámez-Díaz .

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  1. Careggi Hospital, Department of Clinical and Experimental Medicine, University of Florence, Firenze, Italy

    Mario Milco D'Elios

  2. University Medical Centre Freiburg, Department of Rheumatology and Clinical Immunology and Center for Chronic Immunodeficiency, Freiburg, Germany

    Marta Rizzi

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Gámez-Díaz, L. (2019). LRBA Deficiency. In: D'Elios, M., Rizzi, M. (eds) Humoral Primary Immunodeficiencies. Rare Diseases of the Immune System. Springer, Cham. https://doi.org/10.1007/978-3-319-91785-6_10

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  • DOI: https://doi.org/10.1007/978-3-319-91785-6_10

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  • Publisher Name: Springer, Cham

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