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Case Reports
. 2019 Oct;104(10):e483-e486.
doi: 10.3324/haematol.2018.208397. Epub 2019 May 9.

Immunodeficiency, autoimmune thrombocytopenia and enterocolitis caused by autosomal recessive deficiency of PIK3CD-encoded phosphoinositide 3-kinase δ

David J Swan  1 , Dominik Aschenbrenner  2 , Christopher A Lamb  1   3 , Krishnendu Chakraborty  4 , Jonathan Clark  4 , Sumeet Pandey  2 , Karin R Engelhardt  1 , Rui Chen  1 , Athena Cavounidis  2 , Yuchun Ding  5 , Natalio Krasnogor  5 , Christopher D Carey  3 , Meghan Acres  1   3 , Stephanie Needham  3 , Andrew J Cant  3 , Peter D Arkwright  6 , Anita Chandra  4   7 , Klaus Okkenhaug  4   8 , Holm H Uhlig  9   10   11 , Sophie Hambleton  12   3
Affiliations
Case Reports

Immunodeficiency, autoimmune thrombocytopenia and enterocolitis caused by autosomal recessive deficiency of PIK3CD-encoded phosphoinositide 3-kinase δ

David J Swan et al. Haematologica. 2019 Oct.
No abstract available

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Figures

Figure 1.
Figure 1.
PIK3CD mutation in a patient with immunodeficiency and immune dysregulation. (A) Pedigree. (B) Hematoxylin & eosin staining showing colitis and crypt abscess formation. (C) Immunostaining for CD3 (gold) and CD20 (purple); P1, patient; HD, healthy donor. (D) CCR7 and CD45RA staining and quantification of memory CD8+ cells among CD25−CD8+ cells. (E) Expression of perforin and transcription factor TBET in naïve and memory CD8+ T cells. (F) Sanger sequencing confirming frameshift deletion plus 2bp insertion. (G) p110δ schematic showing p.Q170Vfs*41 and previously reported mutations.
Figure 2.
Figure 2.
Functional impact of PIK3CD mutation. (A) Immunoblotting of p110δ, AKT, pAKTT308, pERKT202/Y204, pS6S235/236 and beta-actin in control (HD) and patient (P1) CD4+ and CD8+ T lymphoblasts with and without CD3 stimulation. (B) PIP3 quantification before/after T-cell receptor (TCR) stimulation. (C) and (D) Extracellular acidification rate (Seahorse assay) and quantification of glycolysis in IL-2-stimulated T lymphoblasts of HD and P1 (C) or HD cells treated with idelalisib (D). Three independent experiments with 5-8 technical replicates each; values are plotted as mean of three time points for each injection and each replicate (**P<0.01 and ***P<0.001, Mann-Whitney U test).
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