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Serum levels of cytokines correlate to donor chimerism and acute graft‐vs.‐host disease after haematopoietic stem cell transplantation
Author(s) -
Remberger Mats,
Jaksch Marie,
Uzunel Mehmet,
Mattsson Jonas
Publication year - 2003
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1034/j.1600-0609.2003.00078.x
Subject(s) - medicine , haematopoiesis , transplantation , immunology , hematopoietic stem cell transplantation , stem cell , graft versus host disease , cytokine , tumor necrosis factor alpha , immune system , t cell , gastroenterology , biology , genetics
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.