Clinical, immunologic, molecular analyses and outcomes of iranian patients with LRBA deficiency: A longitudinal study

Pediatr Allergy Immunol. 2017 Aug;28(5):478-484. doi: 10.1111/pai.12735. Epub 2017 Jun 19.

Abstract

Background: LPS-responsive beige-like anchor protein (LRBA) deficiency is a combined immunodeficiency caused by mutation in LRBA gene. The patients have a variety of clinical symptoms including hypogammaglobulinemia, recurrent infections, autoimmunity, and enteropathy.

Methods: A total of 17 LRBA-deficient patients were enrolled in this longitudinal study. For all patients, demographic information, clinical records, laboratory, and molecular data were collected.

Result: Hypogammaglobulinemia was reported in 14 (82.4%), CD4+ T-cell deficiency in five (29.4%), NK cell deficiency in three (21.4%), and CD19+ B-cell deficiency in 11 (64.7%) patients. All patients had history of infectious complications; pneumonia was the most common (76.5%) occurring infection. A history of lymphoproliferative disorders was observed in 14 (82.3%), enteropathy in 13 (76.5%), allergic symptoms in six (35.5%), neurologic problems in four (23.5), and autoimmunity (mostly autoimmune cytopenia) in 13 (76.5%) patients. Sirolimus treatment improved enteropathy of patients with remarkable success. The 20-year overall survival rate declined to 70.6%.

Conclusion: LRBA deficiency has a very broad and variable phenotype and should be considered, especially in children with early-onset hypogammaglobulinemia, severe autoimmune manifestations, enteropathy, lymphoproliferation, and recurrent respiratory tract infections.

Keywords: LRBA; autoimmunity; enteropathy; hypogammaglobulinemia; primary immunodeficiency.

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency*
  • Adaptor Proteins, Signal Transducing / genetics
  • Adolescent
  • Adult
  • Agammaglobulinemia / diagnosis
  • Agammaglobulinemia / etiology
  • Autoimmunity
  • Child
  • Female
  • Genetic Markers
  • Genotype
  • Humans
  • Immunologic Deficiency Syndromes / diagnosis*
  • Immunologic Deficiency Syndromes / etiology
  • Immunologic Deficiency Syndromes / physiopathology
  • Immunologic Deficiency Syndromes / therapy
  • Infant
  • Intestinal Diseases / diagnosis
  • Intestinal Diseases / etiology
  • Iran
  • Longitudinal Studies
  • Lymphoproliferative Disorders / diagnosis
  • Lymphoproliferative Disorders / etiology
  • Male
  • Mutation
  • Phenotype
  • Recurrence
  • Respiratory Tract Infections / diagnosis
  • Respiratory Tract Infections / etiology
  • Treatment Outcome
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Genetic Markers
  • LRBA protein, human