PMID- 10411704
OWN - NLM
STAT- MEDLINE
DCOM- 19990803
LR  - 20220408
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 56
IP  - 1
DP  - 1999 Jul
TI  - Cytokine gene polymorphisms predict acute graft rejection following renal 
      transplantation.
PG  - 281-8
AB  - BACKGROUND: The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) 
      has been implicated in the pathogenesis of acute rejection, while animal models 
      suggest a role for interleukin-10 (IL-10) in promoting graft survival. It has 
      also been shown that polymorphisms in the TNFA gene promoter (position -308) and 
      in the IL-10 gene promoter (position -1082) correlate with differential 
      production of these cytokines in vitro. The aim of this study was to determine 
      whether TNF-alpha and IL-10 gene polymorphisms influence the incidence and 
      severity of acute rejection in the first six months following renal 
      transplantation. METHODS: The cytokine genotypes of 115 consecutive first 
      cadaveric kidney allograft recipients and their donors were screened. The 
      rejection episodes (REs) were defined clinically and confirmed histologically 
      where possible and further classified according to severity (RS), namely 
      steroid-resistant or responsive REs. The genotypes were then correlated with the 
      REs and RS. RESULTS: The recipient TNF-alpha high producer genotype and IL-10 
      high producer genotype were significantly associated with multiple REs (>/=2) in 
      human leukocyte antigen (HLA)-DR mismatched transplants (P = 0.0047 and P = 
      0.045, respectively), whereas only the TNF-alpha high producer genotype was 
      associated with steroid-resistant REs (P = 0.025). When recipient cytokines were 
      analyzed together, the TNF-alpha high/IL-10 high producer genotype had the worst 
      prognosis, whereas TNF-alpha low/IL-10 low producer genotype was protective. 
      CONCLUSIONS: We conclude that recipient TNF-alpha and IL-10 gene polymorphisms 
      are determinants of REs and RS following kidney transplantation. Routine 
      screening of these gene polymorphisms may have a clinical role in identifying 
      patients at risk of multiple REs and severe rejections.
FAU - Sankaran, D
AU  - Sankaran D
AD  - Immunology Research Group, School of Biological Sciences, University of 
      Manchester, England, United Kingdom.
FAU - Asderakis, A
AU  - Asderakis A
FAU - Ashraf, S
AU  - Ashraf S
FAU - Roberts, I S
AU  - Roberts IS
FAU - Short, C D
AU  - Short CD
FAU - Dyer, P A
AU  - Dyer PA
FAU - Sinnott, P J
AU  - Sinnott PJ
FAU - Hutchinson, I V
AU  - Hutchinson IV
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (HLA Antigens)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Cadaver
MH  - Gene Frequency
MH  - Genotype
MH  - Graft Rejection/*epidemiology/*genetics/pathology/physiopathology
MH  - Graft Survival/genetics
MH  - HLA Antigens/analysis
MH  - Histocompatibility Testing
MH  - Humans
MH  - Incidence
MH  - Interleukin-10/*genetics
MH  - *Kidney Transplantation
MH  - Polymorphism, Genetic/*physiology
MH  - Prognosis
MH  - Severity of Illness Index
MH  - Tumor Necrosis Factor-alpha/*genetics
EDAT- 1999/07/20 00:00
MHDA- 1999/07/20 00:01
CRDT- 1999/07/20 00:00
PHST- 1999/07/20 00:00 [pubmed]
PHST- 1999/07/20 00:01 [medline]
PHST- 1999/07/20 00:00 [entrez]
AID - S0085-2538(15)46287-8 [pii]
AID - 10.1046/j.1523-1755.1999.00536.x [doi]
PST - ppublish
SO  - Kidney Int. 1999 Jul;56(1):281-8. doi: 10.1046/j.1523-1755.1999.00536.x.