Immune function is not affected by long-term treatment with monotherapy sirolimus in ALPS patients. (A) ALC significantly improved pre- vs post-sirolimus treatment (P = .039). (B) Quantitative IgG was measured in 6 subjects. Prior to starting sirolimus, the IgG was elevated in 3 children, low in 2, and normal in 1. The IgG normalized in 5 of the 6 children with time (P = .5625). One subject had persistent hypogammaglobulinemia and was diagnosed with comorbid CVID prior to starting sirolimus. Interestingly, the other subject with hypogammaglobulinemia developed it while on chronic MMF, requiring chronic IVIgG replacement for many years. After starting sirolimus, the hypogammaglobulinemia improved. The child was subsequently challenged with vaccines and demonstrated normal antibody response, and was able to discontinue IVIgG supplementation. (C) CD4 and (D) CD8 counts were also studied in 5 ALPS patients pre- and post- long-term administration of sirolimus, with no decrease in number (P = .1875 and P = .3125, respectively). Although not depicted here, 5 ALPS patients had mitogen stimulation measured between 2 and 5 years after initiation of sirolimus, with robust responses to phytohemagglutinin A, concanavalin A, and poke weed mitogen. Measurements post-sirolimus treatment varied per subject, between 1 to 5 years of treatment.