LRBA deficiency with autoimmunity and early onset chronic erosive polyarthritis

Clin Immunol. 2016 Jul;168:88-93. doi: 10.1016/j.clim.2016.03.006. Epub 2016 Apr 5.


LRBA (lipopolysaccharide-responsive and beige-like anchor protein) deficiency associates immune deficiency, lymphoproliferation, and various organ-specific autoimmunity. To date, prevalent symptoms are autoimmune cytopenias and enteropathy, and lymphocytic interstitial lung disease. In 2 siblings from a consanguineous family presenting with early onset polyautoimmunity, we presumed autosomal recessive inheritance and performed whole exome sequencing. We herein report the first case of early-onset, severe, chronic polyarthritis associated with LRBA deficiency. A novel 1bp insertion in the LRBA gene, abolishing protein expression, was identified in this family. Among the 2 brothers homozygous for LRBA mutation, one developed Evans syndrome and deceased at age 8.5 from complications of severe autoimmune thrombocytopenia. His brother, who carried the same homozygous LRBA mutation, early-onset erosive polyarthritis associated with chronic, bilateral, anterior uveitis and early onset type 1 diabetes mellitus. This report widens the clinical spectrum of LRBA deficiency and, in lights of the variable phenotypes described so far, prompts us to screen for this disease in patients with multiple autoimmune symptoms in the family, including severe, erosive, polyarticular juvenile arthritis.

Keywords: Autoimmunity; Exome sequencing; Juvenile idiopathic arthritis; LRBA deficiency; Primary immune deficiency.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adolescent
  • Arthritis / complications
  • Arthritis / genetics*
  • Arthritis / metabolism
  • Autoimmunity / genetics*
  • Child, Preschool
  • Chronic Disease
  • Consanguinity
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / metabolism
  • Exome / genetics
  • Family Health
  • Fatal Outcome
  • Female
  • Humans
  • Immunoblotting
  • Male
  • Mutation*
  • Pedigree
  • Sequence Analysis, DNA
  • Siblings
  • Uveitis, Anterior / complications
  • Uveitis, Anterior / genetics
  • Uveitis, Anterior / metabolism


  • Adaptor Proteins, Signal Transducing
  • LRBA protein, human