Revertant T lymphocytes in a patient with Wiskott-Aldrich syndrome: Analysis of function and distribution in lymphoid organs
Articolo
Data di Pubblicazione:
2010
Citazione:
Revertant T lymphocytes in a patient with Wiskott-Aldrich syndrome: Analysis of function and distribution in lymphoid organs / S. Trifari, S. Scaramuzza, M. Catucci, M. Ponzoni, L. Mollica, R. Chiesa, F. Cattaneo, F. Lafouresse, R. Calvez, W. Vermi, D. Medicina, M.C. Castiello, F. Marangoni, M. Bosticardo, C. Doglioni, M. Caniglia, A. Aiuti, A. Villa, M.-. Roncarolo, L. Dupre. - In: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. - ISSN 0091-6749. - 125:2(2010), pp. 439-448. [10.1016/j.jaci.2009.11.034]
Abstract:
Background: The Wiskott-Aldrich syndrome (WAS) is a rare genetic disease characterized by thrombocytopenia, immunodeficiency, autoimmunity, and hematologic malignancies. Secondary mutations leading to re-expression of WAS protein (WASP) are relatively frequent in patients with WAS. Objective: The tissue distribution and function of revertant cells were investigated in a novel case of WAS gene secondary mutation. Methods: A vast combination of approaches was used to characterize the second-site mutation, to investigate revertant cell function, and to track their distribution over a 18-year clinical follow-up. Results: The WAS gene secondary mutation was a 4-nucleotide insertion, 4 nucleotides downstream of the original deletion. This somatic mutation allowed the T-cell-restricted expression of a stable, full-length WASP with a 3-amino acid change compared with the wild-type protein. WASP+ T cells appeared early in the spleen (age 10 years) and were highly enriched in a mesenteric lymph node at a later time (age 23 years). Revertant T cells had a diversified T-cell-receptor repertoire and displayed in vitro and in vivo selective advantage. They proliferated and produced cytokines normally on T-cell-receptor stimulation. Consistently, the revertant WASP correctly localized to the immunologic synapse and to the leading edge of migrating T cells. Conclusion: Despite the high proportion of functional revertant T cells, the patient still has severe infections and autoimmune disorders, suggesting that re-expression of WASP in T cells is not sufficient to normalize immune functions fully in patients with WAS.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Primary immunodeficiency; secondary mutation; Wiskott-Aldrich syndrome
Elenco autori:
S. Trifari, S. Scaramuzza, M. Catucci, M. Ponzoni, L. Mollica, R. Chiesa, F. Cattaneo, F. Lafouresse, R. Calvez, W. Vermi, D. Medicina, M.C. Castiello, F. Marangoni, M. Bosticardo, C. Doglioni, M. Caniglia, A. Aiuti, A. Villa, M.-. Roncarolo, L. Dupre
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