Discovering monogenic forms of common variable immunogenicity

2012

Challenge

Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiency diagnoses Common Variable Immunodeficiency (CVID), but can take three to five years to be reached due to the non-specific nature of the symptoms. Early diagnosis of CVID is essential to ensuring reduced severity of infections via intravenous immunoglobulin (IVIG) treatment.

Advance

IRP researchers E. Michael Gertz, Ph.D., Alejandro A. Schäffer, Ph.D., and colleagues used genetic linkage analysis in families to identify homozygous mutations in the lipopolysaccharide responsive beige-like anchor gene (LRBA) as a frequent cause of CVID in patients who have early onset and autoimmune manifestations.

Impact

LRBA-deficient patients can now receive a prompt diagnosis via genetic analysis and start IVIG treatment sooner, which helps reduce the severity of recurrent infections and improves overall outcomes.

Publications

Lopez-Herrera G, Tampella G, Pan-Hammarström Q, Herholz P, Trujillo-Vargas CM, Phadwal K, Simon AK, Moutschen M, Etzioni A, Mory A, Srugo I, Melamed D, Hultenby K, Liu C, Baronio M, Vitali M, Philippet P, Dideberg V, Aghamohammadi A, Rezaei N, Enright V, Du L, Salzer U, Eibel H, Pfeifer D, Veelken H, Stauss H, Lougaris V, Plebani A, Gertz EM, Schäffer AA, Hammarström L, Grimbacher B. (2012). Deleterious Mutations in LRBA Are Associated with a Syndrome of Immune Deficiency and Autoimmunity. Am J Hum Genet. 90(6), 986–1001.