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Serum levels of cytokines correlate to donor chimerism and acute graft-vs.-host disease after haematopoietic stem cell transplantation

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Remberger M, Jaksch M, Uzunel M, Mattsson J. Serum levels of cytokines correlate to donor chimerism and acute graft-vs.-host disease after haematopoietic stem cell transplantation.

Eur J Haematol 2003: 70: 384–391. © Blackwell Munksgaard 2003. Abstract: 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)-α and lower levels of transforming growth factor (TGF)-β and interleukin (IL)-10, compared with MC patients. During the first week after SCT, lower levels of TGF-β 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-α, interferon (IFN)-γ and sFas were found among DC patients compared with MC patients. Patients who developed moderate-to-severe acute GVHD had higher levels of TNF-α, IFN-γ, 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-α levels during conditioning and more often developed acute GVHD grades II–IV. Conclusion:

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.
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Keywords: BMT; GVHD; SCT; chimerism; cytokines

Document Type: Research Article

Affiliations: Department of Clinical Immunology and

Publication date: June 1, 2003

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