Investigation of common variable immunodeficiency patients and healthy individuals using autoimmune lymphoproliferative syndrome biomarkers

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of dysregulated lymphocyte homeostasis. Biomarkers including elevated CD3+TCRαβ+CD4−CD8− double negative T cells (TCRαβ+ DNT), IL-10, sCD95L and vitamin B12 can be used to differentiate between ALPS and common variable immunodeficiency (CVID) patients with an overlapping clinical phenotype. We investigated the utility of ALPS biomarkers in 13 CVID patients with lymphoproliferation and/or autoimmune cytopaenia with comparison to 33 healthy controls. Vitamin B12 (P < 0.01) and IL-10 (P < 0.0001), but not sCD95L or TCRαβ+ DNT, were increased in CVID compared to controls. The 95th percentile for TCRαβ+ DNT in healthy controls was used to define a normal range up to 2.3% of total lymphocytes or 3.4% of T cells. These frequencies lie markedly beyond the cut offs used in current ALPS diagnostic criteria (⩾1.5% of total lymphocytes or 2.5% of CD3+ lymphocytes), suggesting these limits may have poor specificity for ALPS.