Identification of amplified clonal T cell populations in the blood of patients with chronic graft-versus-host disease: positive correlation with response to photopheresis.
Chronic graft-versus-host disease (cGVHD) is a multiorgan disorder with skin manifestations resembling scleroderma. Since photopheresis, a treatment that induces an anticlonotypic immune response, has proven to be effective in both cutaneous T cell lymphomas with circulating clonal T cells and in cGVHD, we have searched for circulating clonal T cell populations in patients with cGVHD, and determined whether T cell clonality in the blood is associated with therapeutic response. We screened blood samples from 27 patients after HLA-matched allogeneic bone marrow transplantation (allo-BMT), 10 without cGVHD and 17 with extensive cGVHD, for clonal T cell receptor gamma (TCR gamma) gene rearrangements using fluorescent-based polymerase chain reaction (PCR) and automated high-resolution capillary electrophoresis. Amplified populations of clonal T cells with unique TCR gamma gene rearrangements were found in six of 10 (60%) allo-BMT patients without cGVHD and 13 of 17 (76.5%) allo-BMT patients with cGVHD (P = 0.41), as compared to none of 10 (0%) healthy controls. Twelve patients with cGVHD were treated by photopheresis, and the presence of amplified populations of clonal T cells was found to be associated with a cutaneous response to photopheresis, as eight of eight (100%) clone-positive vs none of four (0%) clone-negative patients experienced a clinically significant cutaneous response to treatment (P = 0.001). Our findings suggest that patients with cGVHD that have detectable expanded clonal T cell populations in their peripheral blood, may be more likely to respond to treatment by photopheresis.
French
L E
LE
Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA.
Alcindor
T
T
Shapiro
M
M
McGinnis
K S
KS
Margolis
D J
DJ
Porter
D
D
Leonard
D G B
DG
Rook
A H
AH
Foss
F
F
D000328:Adult; D015415:Biomarkers; D001773:Blood Cells; D016022:Case-Control Studies; D002908:Chronic Disease; D002999:Clone Cells; D005260:Female; D015321:Gene Rearrangement; D019675:Genes, T-Cell Receptor gamma; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy*; D019337:Hematologic Neoplasms / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D017893:Photopheresis; D011379:Prognosis; D012871:Skin Diseases / Q000209:etiology / Q000628:therapy; D013601:T-Lymphocytes / Q000166:cytology*
D015415:Biomarkers