PMID- 14512310
OWN - NLM
STAT- MEDLINE
DCOM- 20040226
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 103
IP  - 2
DP  - 2004 Jan 15
TI  - IL-13 production by donor T cells is prognostic of acute graft-versus-host 
      disease following unrelated donor stem cell transplantation.
PG  - 717-24
AB  - Despite the success of human leukocyte antigen (HLA) typing in allogeneic stem 
      cell transplantation (SCT) it is rare to find an unrelated donor that is 
      perfectly matched, making identification of "permissive" mismatches of paramount 
      importance. Here, we describe novel associations between donor T-cell cytokine 
      production during donor-antipatient mixed lymphocyte reactions (MLRs) and acute 
      graft-versus-host disease (aGVHD). The data reveal positive correlations between 
      both Th1-type and Th2-type cytokine production and GVHD and the assay established 
      could potentially represent a useful tool for identification of permissible 
      unrelated SCT donors. Associations between interleukin 13 (IL-13) levels and 
      aGVHD were by far the strongest predictor of a GVHD (P =.0002). All patients 
      suffering severe (grade III) aGVHD following SCT had donors who produced very 
      high pretransplantation IL-13 responses, while those developing little or no 
      aGVHD (grades 0-I) produced no IL-13 at all. IL-13 levels were independent of all 
      other cytokines measured as well as cytotoxic T-lymphocyte precursor (CTLp) 
      frequencies. The cytokines IL-5, interferon gamma (IFN-gamma), and tumor necrosis 
      factor alpha (TNF-alpha) also predicted development of aGVHD (P <.05 for all 3), 
      appearing to be coproduced in the assay and correlating with estimated CTLp 
      frequencies. The data challenge the notion that aGVHD is purely a Th1-type 
      cytokine-driven response, high-lighting a novel and highly significant link 
      between the Th2-type cytokine IL-13 and aGVHD.
FAU - Jordan, William J
AU  - Jordan WJ
AD  - Department of Immunology, Faculty of Medicine, Imperial College, Hammersmith 
      Hospital, Du Cane Rd, London W12 0NN, United Kingdom. w.jordan1@ic.ac.uk
FAU - Brookes, Paul A
AU  - Brookes PA
FAU - Szydlo, Richard M
AU  - Szydlo RM
FAU - Goldman, John M
AU  - Goldman JM
FAU - Lechler, Robert I
AU  - Lechler RI
FAU - Ritter, Mary A
AU  - Ritter MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030925
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-13)
SB  - IM
MH  - Adult
MH  - Blast Crisis/immunology
MH  - Cytokines/blood
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Graft vs Host Disease/epidemiology/*immunology/mortality
MH  - Histocompatibility Testing
MH  - Humans
MH  - Interleukin-13/*blood/immunology
MH  - Lymphocyte Culture Test, Mixed
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Stem Cell Transplantation/*adverse effects
MH  - T-Lymphocytes/*immunology
MH  - Th1 Cells/*immunology
MH  - Th2 Cells/*immunology
MH  - Time Factors
MH  - Transplantation, Homologous/adverse effects
EDAT- 2003/09/27 05:00
MHDA- 2004/02/27 05:00
CRDT- 2003/09/27 05:00
PHST- 2003/09/27 05:00 [pubmed]
PHST- 2004/02/27 05:00 [medline]
PHST- 2003/09/27 05:00 [entrez]
AID - S0006-4971(20)54663-6 [pii]
AID - 10.1182/blood-2003-01-0192 [doi]
PST - ppublish
SO  - Blood. 2004 Jan 15;103(2):717-24. doi: 10.1182/blood-2003-01-0192. Epub 2003 Sep 
      25.