T cell deficiency associated with downregulation of GPI-anchored proteins

We describe an adult patient with chronic lymphocytic inflammation of the skin, severe T cell lymphopenia and global loss of Glycosylphosphatidylinositol-anchored proteins (GPI-AP) on a large proportion of T cells in blood and skin lesions with red blood cells being in the normal range. Glycosylphosphatidylinositol (GPI) is a common posttranscriptional modification of cell surface proteins to anchor them to the plasma membrane. We aim to identify the cause of the GPI-AP defect in this patient and its link to T cell deficiency in peripheral blood and T cell infiltration in the skin. Classical proteins involved in GPI anchor biosynthesis are neither mutated as shown by whole exome sequencing nor dysregulated on RNA or protein level. As transcription of GPI-AP is normal, we assessed if the defect occurs early during translation or during protein transportation to the plasma membrane. Our results indicate that GPI-AP biosynthesis is impaired at an early stage as GPI-AP are neither trapped within the ER-Golgi nor are they released into the supernatant. It remains to be resolved if GPI-AP translation is not initiated or fails prematurely resulting in degradation of the GPI-AP. Phenotypically, in the blood CD8 T cells predominate with an almost diminished naïve T cell population. The remaining CD4 T cells are mainly composed of Th2 cells producing IL-13 and IL-5. Around 60 % of blood-derived T cells express cutaneous lymphocyte antigen, CCR4 and CCR10, being markers for extensive skin homing of T cells. We present here for the first time a patient with loss of GPI-AP exclusively in the T cell compartment, allowing to explore the role of GPI-AP for T cell function. We conclude that the massive T cell homing to the skin observed in this patient results in lymphopenia in the blood.