Characterization of thymic architecture and lymphocyte populations in X-MAID due to an underlying pathogenic moesin mutation

Background: X-linked Moesin Associated Immunodeficiency (X-MAID) is a combined immunodeficiency caused by deficiency in the moesin protein. Moesin, which is encoded by the MSN gene, is part of the ezrin-radixin-moesin (ERM) family of transmembrane proteins that interact with the actin cytoskeleton and regulate the shape and migration of cells. Deficiency of moesin is associated with aberrant T cell migration and inadequate immune synapse formation, leading to significant immunodeficiency and recurrent infections. While the clinical presentation of XMAID is diverse, to date, no thymus histopathology findings have been reported. Aim: Describe the thymus histopathology of a patient with X-MAID. Results: Our patient is a 10-year-old male who presented early in life with recurrent infections, dysmorphic features, and severe pulmonary venous stenosis which required a double lung transplant at the age of 4 years. Prior to transplant, he was referred to Immunology for assessment and was subsequently found to harbour a hemizygous variant in the MSN gene (c.278dupT; L93FfsX21). Thymus histophathology findings showed significant cortical atrophy and dysplasia, and was accompanied by reduction in CD3+ cells in the cortex. Abnormally low numbers of suppressor T cells and T helper cells in the thymic cortex and medulla were noted. Conclusion: Thymic findings in X-MAID can include cortical atrophy, dysplasia, and decreased cellularity. This provides further evidence for the importance of moesin on T cell development and migration in the thymus. Statement of Novelty: Description of thymus histopathology in a patient with X-MAID