First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID): a report of 2 cases.
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.
Markert
M Louise
ML
Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. marke001@mc.duke.edu
Marques
José G
JG
Neven
Bénédicte
B
Devlin
Blythe H
BH
McCarthy
Elizabeth A
EA
Chinn
Ivan K
IK
Albuquerque
Adriana S
AS
Silva
Susana L
SL
Pignata
Claudio
C
de Saint Basile
Geneviève
G
Victorino
Rui M
RM
Picard
Capucine
C
Debre
Marianne
M
Mahlaoui
Nizar
N
Fischer
Alain
A
Sousa
Ana E
AE
D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000172:deficiency*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008297:Male; D016511:Severe Combined Immunodeficiency / Q000276:immunology* / Q000503:physiopathology* / Q000601:surgery*; D013950:Thymus Gland / Q000637:transplantation*
D051858:Forkhead Transcription Factors; C090140:Whn protein