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

Abstract

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/mm(3) and 1232/mm(3) CD3(+) cells, 647/mm(3) and 868/mm(3) CD4(+) T cells, 213/mm(3) and 425/mm(3) 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 discontinued immunoglobulin replacement. In summary, thymus transplantation led to T-cell reconstitution and function in these FOXN1 deficient infants.

• Authors: M Louise Markert, José G Marques, Bénédicte Neven, Blythe H Devlin, Elizabeth A McCarthy, Ivan K Chinn, Adriana S Albuquerque, Susana L Silva, Claudio Pignata, Geneviève de Saint Basile, Rui M Victorino, Capucine Picard, Marianne Debre, Nizar Mahlaoui, Alain Fischer, Ana E Sousa
• Journal: Blood (Blood) Vol. 117 Issue 2 Pg. 688-96 (Jan 13 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 20978268 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Forkhead Transcription Factors
• Whn protein

Topics

• Cell Separation
• Female
• Flow Cytometry
• Forkhead Transcription Factors (deficiency)
• Humans
• Immunophenotyping
• Infant
• Male
• Severe Combined Immunodeficiency (immunology, physiopathology, surgery)
• Thymus Gland (transplantation)