Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy

Mutations in the LRBA gene (encoding the lipopolysaccharide-responsive and beige-like anchor protein) cause a syndrome of autoimmunity, lymphoproliferation, and humoral immune deficiency. The biological role of LRBA in immunologic disease is unknown. We found that patients with LRBA deficiency manifested a dramatic and sustained improvement in response to abatacept, a CTLA4 (cytotoxic T lymphocyte antigen-4)-immunoglobulin fusion drug. Clinical responses and homology of LRBA to proteins controlling intracellular trafficking led us to hypothesize that it regulates CTLA4, a potent inhibitory immune receptor. We found that LRBA colocalized with CTLA4 in endosomal vesicles and that LRBA deficiency or knockdown…

• AS
  American Society of Hematology
• M
  Merck
• CC
  Cincinnati Children's Hospital Medical Center
• NI
  National Institutes of Health

  Award: 1RC2 HG005608
• NI
  National Institute of Allergy and Infectious Diseases