title: Successful Hematopoietic Stem Cell Transplantation in a Patient with LPS-Responsive Beige-Like Anchor (LRBA) Gene Mutation.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Our data suggest a beneficial effect of HSCT in patients with LRBA deficiency.
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. bianca.tesi@ki.se.|Clinical Genetics Unit, Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. bianca.tesi@ki.se.
authors.forename: Bianca
authors.initials: B
authors.lastname: Tesi
authors.affiliation: Astrid Lindgren Children's Hospital, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Priftakis
authors.affiliation: Astrid Lindgren Children's Hospital, Karolinska University Hospital Huddinge, Stockholm, Sweden.|Department of Clinical Science Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lindgren
authors.affiliation: Centre for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Samuel C C
authors.initials: SC
authors.lastname: Chiang
authors.affiliation: Department of Clinical Science Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.|Department of Radiology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kartalis
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.|Clinical Genetics Unit, Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Löfstedt
authors.affiliation: Department of Pathology, University Hospital Karolinska Huddinge, Solna, Sweden.|Department of Pathology, Skåne University Hospital, Lund, Sweden.
authors.forename: Esther
authors.initials: E
authors.lastname: Lörinc
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: Jan-Inge
authors.initials: JI
authors.lastname: Henter
authors.affiliation: Astrid Lindgren Children's Hospital, Karolinska University Hospital Huddinge, Stockholm, Sweden.|Department of Clinical Science Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Jacek
authors.initials: J
authors.lastname: Winiarski
authors.affiliation: Centre for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Yenan T
authors.initials: YT
authors.lastname: Bryceson
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. Marie.Meeths@ki.se.|Clinical Genetics Unit, Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. Marie.Meeths@ki.se.
authors.forename: Marie
authors.initials: M
authors.lastname: Meeths
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000744:Anemia, Hemolytic, Autoimmune / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D002648:Child; D017074:Common Variable Immunodeficiency / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D006680:HLA Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D017384:Sequence Deletion / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006680:HLA Antigens; D007136:Immunoglobulins; C428703:LRBA protein, human
keywords: acute disseminated encephalomyelitis; common variable immune deficiency; enteropathy; hematopoietic stem cell transplantation; primary immunodeficiency; whole exome sequencing