title: Cytokines and chronic rejection: a study in kidney transplant long-term survivors.
abstract: BACKGROUND
  In part, the long-term survival of kidney transplants depends on the efforts to perform grafts with good human leukocyte antigen (HLA) compatibility, but there are other mechanisms that must induce some sort of tolerance and impair the anti-graft immune reaction. Because cytokines are one of the main components of immune response, we evaluated single nucleotide polymorphisms (SNPs) of several cytokine genes that may influence the production of a given cytokine and therefore the features of immune reactions.
  
  
  METHODS
  A total of 416 first cadaveric kidney transplants were monitored for HLA matching. After 10 years, the graft was still functional in 171 of 416 patients; 102 of 171 patients were also typed for cytokine polymorphisms.
  
  
  RESULTS
  The mismatch distributions in patients who underwent transplantation were not statistically different from the entire group of patients who underwent transplantation during the same time period. Moreover, it seems that almost all of the HLA class I incompatible long-term survivors are homozygous for GG at the -1082 interleukin (IL)-10 or CC at the -33IL4.
  
  
  CONCLUSIONS
  We observed that a match for class I and class II HLA antigens apparently does not favor the long-term survival of transplanted kidneys. In fact, matched grafts are lost before 10 years in the same proportion as the mismatched grafts. We also demonstrated (1) that patients who are homozygous for GG at the SNP -1082IL10 (high IL-10 producers) and HLA class I mismatched (but matched for class II) are protected from chronic rejection, and (2) that patients who are homozygous for CC at the SNP -33IL4 (low IL-4 producers) and HLA class I mismatched (regardless of matching for class II) are protected from chronic rejection.
authors.affiliation: Genetics Institute, Department of Genetics, Biology and Biochemistry, University of Torino, Torino, Piemonte, Italy. federicauboldi@tiscali.it
authors.forename: Mariafederica
authors.initials: M
authors.lastname: Uboldi de Capei
authors.forename: Ennia
authors.initials: E
authors.lastname: Dametto
authors.forename: Maria E
authors.initials: ME
authors.lastname: Fasano
authors.forename: Maria
authors.initials: M
authors.lastname: Messina
authors.forename: Loredana
authors.initials: L
authors.lastname: Pratico'
authors.forename: Sabina
authors.initials: S
authors.lastname: Rendine
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Segoloni
authors.forename: Emilio S
authors.initials: ES
authors.lastname: Curtoni
mesh_terms: D001787:Blood Group Incompatibility; D002102:Cadaver; D003596:Cytosine; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics*; D006085:Graft Survival; D006147:Guanine; D006648:Histocompatibility; D006720:Homozygote; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D016030:Kidney Transplantation; D008137:Longitudinal Studies; D020641:Polymorphism, Single Nucleotide; D013997:Time Factors; D014019:Tissue Donors
chemical_list: D016753:Interleukin-10; D015847:Interleukin-4; D006147:Guanine; D003596:Cytosine