Figure 1.

Imaging, bone marrow biopsy findings and characterization and location of the novel FAS heterozygous variant in a patient with CD4 lymphopenia and ALPS. (A) Computed tomography of abdomen and pelvis. (1) Coronal section: Splenomegaly. (2) Splenic volume estimation by 3D reconstruction: 1,034 milliliter (mL) (normal 200 ± 50 mL). (3) Axial section: Paraortic and mesenteric lymphadenopathy. (B) Bone marrow biopsy showing scattered lymphocytic aggregates with prevalence of CD8⁺ cells. (1) Lymphocytic aggregate in hematoxylin and eosin staining at 200x magnification. (2) CD3 Immunohistochemistry (IHC) staining. (3) CD8 IHC staining. (C) Diagram of the FAS gene identifying intron/exon structure and protein domains. Mutations are indicated at their approximate location and identified by symbols corresponding to mutation type. The new mutation identified in the index patient indicated by the red arrow. Figure adapted by Hsu et al. (3). (D) FAS-induced apoptosis was evaluated in terminal effector memory cells (TEM) and TCRαβ⁺ DN T cells of index patient and healthy subjects using an ex vivo flow cytometric assay based on FAS crosslinking. (1) Average fold increase ± standard error of mean (SEM) of Annexin-V expression in TEM (CD45RA⁻CCR7⁻CD27⁻) from 4 independent experiments with index patient (red) and 8 different healthy controls (blue) with different concentrations of anti-FAS crosslinking antibody. (2) Average fold increase ± SEM of Annexin-V expression in DNT cells (TCRαβ⁺CD4⁻CD8⁻) from 4 independent experiments with index patient (green) and 8 different healthy controls (purple) with different concentrations of anti-FAS crosslinking antibody.