First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID): a report of 2 cases

• Published in: Blood Vol. 117; no. 2; pp. 688 - 696
• Main Authors: Markert, M. Louise, Marques, José G., Neven, Bénédicte, Devlin, Blythe H., McCarthy, Elizabeth A., Chinn, Ivan K., Albuquerque, Adriana S., Silva, Susana L., Pignata, Claudio, de Saint Basile, Geneviève, Victorino, Rui M., Picard, Capucine, Debre, Marianne, Mahlaoui, Nizar, Fischer, Alain, Sousa, Ana E.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 13.01.2011; Americain Society of Hematology; American Society of Hematology
• Series: Transplantation
• Subjects: Biological and medical sciences; Cell Separation; Female; Flow Cytometry; Forkhead Transcription Factors - deficiency; Hematologic and hematopoietic diseases; Humans; Immunophenotyping; Infant; Male; Medical sciences; Severe Combined Immunodeficiency - immunology; Severe Combined Immunodeficiency - physiopathology; Severe Combined Immunodeficiency - surgery; Thymus Gland - transplantation; Transplantation; Case study; Thymus gland; Treatment; Hematology; Surgery; Deficiency; Graft; Transplantation
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2010-06-292490

FOXN1 deficiency is a primary immunodeficiency characterized by athymia, alopecia totalis, and nail dystrophy. Two infants with FOXN1 deficiency were transplanted with cultured postnatal thymus tissue. Subject 1 presented with disseminated Bacillus Calmette-Guérin infection and oligoclonal T cells with no naive markers. Subject 2 had respiratory failure, human herpes virus 6 infection, cytopenias, and no circulating T cells. The subjects were given thymus transplants at 14 and 9 months of life, respectively. Subject 1 received immunosuppression before and for 10 months after transplantation. With follow up of 4.9 and 2.9 years, subjects 1 and 2 are well without infectious complications. The pretransplantation mycobacterial disease in subject 1 and cytopenias in subject 2 resolved. Subject 2 developed autoimmune thyroid disease 1.6 years after transplantation. Both subjects developed functional immunity. Subjects 1 and 2 have 1053/mm3 and 1232/mm3 CD3+ cells, 647/mm3 and 868/mm3 CD4+ T cells, 213/mm3 and 425/mm3 naive CD4+ T cells, and 10 200 and 5700 T-cell receptor rearrangement excision circles per 100 000 CD3+ cells, respectively. They have normal CD4 T-cell receptor β variable repertoires. Both subjects developed antigen-specific proliferative responses and have discon-tinued immunoglobulin replacement. In summary, thymus transplantation led to T-cell reconstitution and function in these FOXN1 deficient infants.