Serum levels of cytokines correlate to donor chimerism and acute graft-vs.-host disease after haematopoietic stem cell transplantation.
BACKGROUND
Some patients become full donor chimeras (DC) early after stem-cell transplantation (SCT), while others remain mixed chimeras for a longer time. Little is known about the mechanism behind these phenomena.


METHODS
Serum cytokine levels during conditioning and during the first month after SCT were analysed in 30 patients. Of the 21 patients who became full T-cell DC from the first analysed sample, 12 developed grade II-IV acute graft-vs.-host disease (GVHD) and the other nine, mild or no acute GVHD. Another nine patients were T-cell mixed chimeras (MC). All MC patients had no or mild acute GVHD.


RESULTS
During the pretransplant conditioning, DC patients had higher levels of tumour necrosis factor (TNF)-alpha and lower levels of transforming growth factor (TGF)-beta and interleukin (IL)-10, compared with MC patients. During the first week after SCT, lower levels of TGF-beta and IL-10 and higher levels of soluble Fas (sFas) were found in DC patients compared with MC patients. During the second and third weeks after SCT, increased levels of TNF-alpha, interferon (IFN)-gamma and sFas were found among DC patients compared with MC patients. Patients who developed moderate-to-severe acute GVHD had higher levels of TNF-alpha, IFN-gamma, IL-10 and sFas at 2 weeks post-SCT than in those with less GVHD. Patients homozygous for the TNFd microsatellite alleles 3 or 4 had significantly higher TNF-alpha levels during conditioning and more often developed acute GVHD grades II-IV.


CONCLUSIONS
These results indicate that an imbalance between pro-inflammatory and immune- modulating cytokines are involved in the development of chimerism and acute GVHD after allo-SCT. The Fas/FasL pathway is probably involved in the elimination of recipient cells leading to full donor chimerism.
Remberger
Mats
M
Department of Clinical Immunology and Centre for Allogeneic Stem Cell Transplantation, Huddinge University Hospital, Stockholm, Sweden. mats.remberger@labmed.ki.se
Jaksch
Marie
M
Uzunel
Mehmet
M
Mattsson
Jonas
J
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes; D018183:Transplantation Chimera; D019014:fas Receptor / Q000097:blood
D016207:Cytokines; D019014:fas Receptor