Prediction of acute graft-versus-host disease and detection of distinct end-organ targets by enumeration of peripheral blood cytokine spot-forming cells.
BACKGROUND
Acute graft-versus-host disease (aGVHD) remains a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. It was hypothesized that type 1 cytokines promoted aGVHD and type 2 cytokines inhibited it. However, recent publications demonstrated contradictory results in murine models. Type 1/2 paradigm in aGVHD remains to be determined in human.


METHODS
Using enzyme-linked immunospot assay that reflects ongoing immune status in vivo, we measured spot-forming cells (SFCs) for interferon (IFN)-gamma, interleukin (IL)-12, IL-4, and IL-10 in peripheral blood from 56 patients with hematological disorders who underwent allogeneic hematopoietic stem cell transplantation.


RESULTS
The numbers of IFN-gamma and IL-4 SFCs in patients with grade II approximately IV aGVHD were significantly higher than those in patients with grade 0 approximately I aGVHD. The enumeration of cytokine SFCs predicted aGVHD approximately 4 days before it became clinically evident, since IFN-gamma SFCs in asymptomatic phase that later progressed into grade II approximately IV aGVHD were elevated in 8 out of 8 evaluable patients. Similarly, IL-4 SFCs were elevated in 6 of 8 patients. In addition, Type 1 cytokine SFCs contributed to the intestinal, but not skin and hepatic aGVHD.


CONCLUSIONS
Enzyme-linked immunospot assay is clinically useful for predicting aGVHD and detecting distinct end-organ targets following allogeneic hematopoietic stem cell transplantation.
Hirayama
Masahiro
M
Department of Pediatrics and Cell Transplantation, Mie University School of Medicine, Tsu, Mie, Japan.
Azuma
Eiichi
E
Kumamoto
Tadashi
T
Iwamoto
Shotaro
S
Yamada
Hiroshi
H
Nashida
Yuji
Y
Araki
Mariko
M
Kageyama
Shinichi
S
Tamaki
Shigehisa
S
Kawakami
Keiki
K
Yamamoto
Hatsumi
H
Komada
Yoshihiro
Y
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005190:Family; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology*; D006801:Humans; D007223:Infant; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011237:Predictive Value of Tests; D033581:Stem Cell Transplantation; D013997:Time Factors; D014184:Transplantation, Homologous
D016207:Cytokines