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Successful Hematopoietic Stem Cell Transplantation in a Patient with LPS-Responsive Beige-Like Anchor (LRBA) Gene Mutation

Tesi, Bianca; Priftakis, Peter; Lindgren, Fredrik; Chiang, Samuel C C; Kartalis, Nikolaos; Löfstedt, Alexandra; Lörinc, Esther LU ; Henter, Jan Inge; Winiarski, Jacek and Bryceson, Yenan T., et al. (2016) In Journal of Clinical Immunology 36(5). p.480-489
Abstract

Purpose: Autosomal recessive mutations in LRBA, encoding for LPS-responsive beige-like anchor protein, were described in patients with a common variable immunodeficiency (CVID)-like disease characterized by hypogammaglobulinemia, autoimmune cytopenias, and enteropathy. Here, we detail the clinical, immunological, and genetic features of a patient with severe autoimmune manifestations. Methods: Whole exome sequencing was performed to establish a molecular diagnosis. Evaluation of lymphocyte subsets was performed for immunological characterization. Medical files were reviewed to collect clinical and immunological data. Results: A 7-year-old boy, born to consanguineous parents, presented with autoimmune hemolytic anemia,... (More)

Purpose: Autosomal recessive mutations in LRBA, encoding for LPS-responsive beige-like anchor protein, were described in patients with a common variable immunodeficiency (CVID)-like disease characterized by hypogammaglobulinemia, autoimmune cytopenias, and enteropathy. Here, we detail the clinical, immunological, and genetic features of a patient with severe autoimmune manifestations. Methods: Whole exome sequencing was performed to establish a molecular diagnosis. Evaluation of lymphocyte subsets was performed for immunological characterization. Medical files were reviewed to collect clinical and immunological data. Results: A 7-year-old boy, born to consanguineous parents, presented with autoimmune hemolytic anemia, hepatosplenomegaly, autoimmune thyroiditis, and severe autoimmune gastrointestinal manifestations. Immunological investigations revealed low immunoglobulin levels and low numbers of B and NK cells. Treatment included immunoglobulin replacement and immunosuppressive therapy. Seven years after disease onset, the patient developed severe neurological symptoms resembling acute disseminated encephalomyelitis, prompting allogeneic hematopoietic stem cell transplantation (HSCT) with the HLA-identical mother as donor. Whole exome sequencing of the patient uncovered a homozygous 1 bp deletion in LRBA (c.7162delA:p.T2388Pfs*7). Importantly, during 2 years of follow-up post-HSCT, marked clinical improvement and recovery of immune function was observed. Conclusions: Our data suggest a beneficial effect of HSCT in patients with LRBA deficiency.

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published
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keywords
acute disseminated encephalomyelitis, common variable immune deficiency, enteropathy, hematopoietic stem cell transplantation, primary immunodeficiency, whole exome sequencing
in
Journal of Clinical Immunology
volume
36
issue
5
pages
10 pages
publisher
Springer
external identifiers
  • Scopus:84965058557
ISSN
0271-9142
DOI
10.1007/s10875-016-0289-y
language
English
LU publication?
yes
id
f05d78ac-7a97-4522-8970-370dbddb59ca
date added to LUP
2016-05-31 15:59:56
date last changed
2016-11-20 04:33:54
@misc{f05d78ac-7a97-4522-8970-370dbddb59ca,
  abstract     = {<p>Purpose: Autosomal recessive mutations in LRBA, encoding for LPS-responsive beige-like anchor protein, were described in patients with a common variable immunodeficiency (CVID)-like disease characterized by hypogammaglobulinemia, autoimmune cytopenias, and enteropathy. Here, we detail the clinical, immunological, and genetic features of a patient with severe autoimmune manifestations. Methods: Whole exome sequencing was performed to establish a molecular diagnosis. Evaluation of lymphocyte subsets was performed for immunological characterization. Medical files were reviewed to collect clinical and immunological data. Results: A 7-year-old boy, born to consanguineous parents, presented with autoimmune hemolytic anemia, hepatosplenomegaly, autoimmune thyroiditis, and severe autoimmune gastrointestinal manifestations. Immunological investigations revealed low immunoglobulin levels and low numbers of B and NK cells. Treatment included immunoglobulin replacement and immunosuppressive therapy. Seven years after disease onset, the patient developed severe neurological symptoms resembling acute disseminated encephalomyelitis, prompting allogeneic hematopoietic stem cell transplantation (HSCT) with the HLA-identical mother as donor. Whole exome sequencing of the patient uncovered a homozygous 1 bp deletion in LRBA (c.7162delA:p.T2388Pfs*7). Importantly, during 2 years of follow-up post-HSCT, marked clinical improvement and recovery of immune function was observed. Conclusions: Our data suggest a beneficial effect of HSCT in patients with LRBA deficiency.</p>},
  author       = {Tesi, Bianca and Priftakis, Peter and Lindgren, Fredrik and Chiang, Samuel C C and Kartalis, Nikolaos and Löfstedt, Alexandra and Lörinc, Esther and Henter, Jan Inge and Winiarski, Jacek and Bryceson, Yenan T. and Meeths, Marie},
  issn         = {0271-9142},
  keyword      = {acute disseminated encephalomyelitis,common variable immune deficiency,enteropathy,hematopoietic stem cell transplantation,primary immunodeficiency,whole exome sequencing},
  language     = {eng},
  number       = {5},
  pages        = {480--489},
  publisher    = {ARRAY(0x947ff58)},
  series       = {Journal of Clinical Immunology},
  title        = {Successful Hematopoietic Stem Cell Transplantation in a Patient with LPS-Responsive Beige-Like Anchor (LRBA) Gene Mutation},
  url          = {http://dx.doi.org/10.1007/s10875-016-0289-y},
  volume       = {36},
  year         = {2016},
}