Acute graft-versus-host disease transiently impairs thymic output in young patients after allogeneic hematopoietic stem cell transplantation.
Long-term T-cell reconstitution after hematopoietic stem cell transplantation (HSCT) is dependent on patient thymic function and affected by graft-versus-host disease (GVHD). To assess the impact of acute GVHD (aGVHD) on thymic function, we followed a cohort of 93 patients who received HSCT from a human histocompatibility leukocyte antigen-identical sibling, mainly for hematologic malignancies. Thymic output was measured by signal-joint T-cell receptor excision circles (sjTREC) real-time polymerase chain reaction. Absolute sjTREC number was lower at 6 months in patients with aGVHD (P = .014), associated with lower absolute counts of naive CD4 T cells at 6 and 12 months (P = .04 and .02), and persistent abnormalities in T-cell repertoire diversity. Age and aGVHD affected thymic function independently in multivariate analysis. In patients less than 25 years of age, thymic function recovered almost totally at 1 year. As a marker of thymocyte proliferation, we quantified the betaTREC generated during the T-cell receptor beta-chain recombination, in a group of 20 age-matched patients. Mean betaTREC level was reduced at 6 months in patients with aGVHD, indicating an impact on early thymic differentiation rather than on intrathymic proliferation. These data show that aGVHD or its treatment has a transient impact on thymic function in younger patients in the first months after HSCT.
Clave
Emmanuel
E
Assistance Publique-Hôpitaux de Paris, Inserm Unite Mixte de Recherche, Institut Universitaire d'Hématologie, Université Paris, Diderot, France. emmanuel.clave@univ-paris-diderot.fr
Busson
Marc
M
Douay
Corinne
C
Peffault de Latour
Régis
R
Berrou
Jeannig
J
Rabian
Claire
C
Carmagnat
Maryvonnick
M
Rocha
Vanderson
V
Charron
Dominique
D
Socié
Gérard
G
Toubert
Antoine
A
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D005260:Female; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007165:Immunosuppression Therapy; D038041:Lymphopoiesis; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D014184:Transplantation, Homologous / Q000009:adverse effects*; D055815:Young Adult
D016692:Receptors, Antigen, T-Cell, gamma-delta