Characterization of thymic architecture and lymphocyte populations in X-MAID due to an underlying pathogenic moesin mutation
Abstract
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 X-MAID 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; p.L93FfsX21). Thymus histopathology 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.
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REFERENCES
Abrego Fuentes L., Mandola A.B., and Ngan B. 2023. Lung histopathology evaluation of an X-MAID patient with a novel mutation in MSN. LymphoSign J. 10: 1–6.
Avery L., Robertson T.F., Wu C.F., Roy N.H., Chauvin S.D., Perkey E., Vanderbeck A., Maillard I., and Burkhardt J.K. 2022. A murine model of X-Linked moesin-associated immunodeficiency (X-MAID) reveals defects in T cell homeostasis and migration. Front. Immunol. 12: 726406.
Bogue, M., Gilfillan, S., Benoist, C., and Mathis, D. 1992. Regulation of N-region diversity in antigen receptors through thymocyte differentiation and thymus ontogeny. Proc. Natl. Acad. Sci. 89: 11011–11015. 1438306.
Bradshaw G., Lualhati R.R., Albury C.L., Maksemous N., Roos-Araujo D., Smith R.A., Benton M.C., Eccles D.A., Lea R.A., Sutherland H.G., and Haupt L.M. 2018. Exome sequencing diagnoses X-linked moesin-associated immunodeficiency in a primary immunodeficiency case. Front. Immunol. 9: 420.
Chen E.J., Shaffer M.H., Williamson E.K., Huang Y., and Burkhardt J.K. 2013. Ezrin and moesin are required for efficient T cell adhesion and homing to lymphoid organs. PLoS One, 8: e52368.
Delmonte O.M., Biggs C.M., Hayward A., Comeau A.M., Kuehn H.S., Rosenzweig S.D., and Notarangelo L.D. 2017. First case of X-linked moesin deficiency identified after newborn screening for SCID. J. Clin. Immunol. 37: 336–338.
Fang Y., Luo Y., Liu Y., and Chen J. 2022. A novel variant of X-linked moesin gene in a boy with inflammatory bowel disease like disease: A case report. Front. Genet. 13: 873635.
Fehon R.G., McClatchey A.I., and Bretscher A. 2010. Organizing the cell cortex: the role of ERM proteins. Nat. Rev. Mol. Cell Biol. 11: 276–287.
Hale L.P. 2004. Histologic and molecular assessment of human thymus. Ann. Diagn. Pathol. 8: 50–60.
Henrickson S.E., Andre-Schmutz I., Lagresle-Peyrou C., Deardorff M.A., Jyonouchi H., Neven B., Bunin N., and Heimall J.R. 2019. Hematopoietic stem cell transplant for the treatment of X-MAID. Front. Pediatr. 7: 170.
Hirata T., Nomachi A., Tohya K., Miyasaka M., Tsukita S., Watanabe T., and Narumiya S. 2012. Moesin-deficient mice reveal a non-redundant role for moesin in lymphocyte homeostasis. Int. Immunol. 24: 705–717.
Jones J.F., Meyskens F.L., Henley M.J., Schmalstieg F.C., and Hong R. 1982. Terminal deoxynucleotidyl transferase activity in thymus biopsies of immunodeficient patients. Thymus, 4: 287–297.
Kovács A.L., Kárteszi J., Prohászka Z., Kalmár T., Késmárky G., Koltai K., Nagy Z., Sebők J., Vas T., Molnár K., and Berki T. 2022. Hemizygous nonsense variant in the moesin gene (MSN) leads to a new autoimmune phenotype of Immunodeficiency 50. Front. Immunol. 13: 919411.
Lagresle-Peyrou C., Luce S., Ouchani F., Soheili T.S., Sadek H., Chouteau M., Durand A., Pic I., Majewski J., Brouzes C., Lambert N., Bohineust A., Verhoeyen E., Cosset F.L., Magerus-Chatinet A., Rieux-Laucat F., Gandemer V., Monnier D., Heijmans C., van Gijn M., Dalm V.A., Mahlaoui N., Stephan J.L., Picard C., Durandy A., Kracker S., Hivroz C., Jabado N., de Saint Basile G., Fischer A, Cavazzana M., and André-Schmutz I. 2016. X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene. J. Allergy Clin. Immunol. 138: 1681–1689.e8.
Masumoto J., Sagara J., Hayama M., Hidaka E., Katsuyama T., and Taniguchi S.I. 1998. Differential expression of moesin in cells of hematopoietic lineage and lymphatic systems. Histochem. Cell Biol. 110: 33–41.
Poliani P.L., Vermi W., and Facchetti F. 2009. Thymus microenvironment in human primary immunodeficiency diseases. Curr. Opinion Allergy Clin. Immunol. 9: 489–495.
Pore D., Bodo J., Danda A., Yan D., Phillips J.G., Lindner D., Hill B.T., Smith M.R., Hsi E.D., and Gupta N. 2015. Identification of Ezrin-Radixin-Moesin proteins as novel regulators of pathogenic B-cell receptor signaling and tumor growth in diffuse large B-cell lymphoma. Leukemia, 29: 1857–1867.
Rodewald H.R. 2008. Thymus organogenesis. Annu. Rev. Immunol. 26: 355–388.
Shaffer M.H., Huang Y., Corbo E., Wu G.F., Velez M., Choi J.K., Saotome I., Cannon J.L., McClatchey A.I., Sperling A.I., and Maltzman J.S. 2010. Ezrin is highly expressed in early thymocytes, but dispensable for T cell development in mice. PloS One, 5: e12404.
Urdinez L., Goris V., Falbo J., Oleastro M., and Danielian S. 2021. Argentinian X-MAID siblings with one of them manifesting a rare ophthalmological complication. J. Clin. Immunol. 41: 1960–1963.
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LymphoSign Journal
Volume 11 • Number 2 • June 2024
Pages: 38 - 44
History
Received: 15 May 2024
Accepted: 10 June 2024
Accepted manuscript online: 10 June 2024
Version of record online: 12 August 2024
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© 2024.
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AbdulrahmanAl Ghamdi, LindaVong, ChaimM. Roifman, and BoNgan. 2024. Characterization of thymic architecture and lymphocyte populations in X-MAID due to an underlying pathogenic moesin mutation. LymphoSign Journal.
11(2): 38-44. https://doi.org/10.14785/lymphosign-2024-0005
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