Intragraft expression of the IL-10 gene is up-regulated in renal protocol biopsies with early interstitial fibrosis, tubular atrophy, and subclinical rejection.
Grafts with subclinical rejection associated with interstitial fibrosis and tubular atrophy (SCR+IF/TA) show poorer survival than grafts with subclinical rejection without IF/TA (SCR). Aiming to detect differences among SCR+IF/TA and SCR, we immunophenotyped the inflammatory infiltrate (CD45, CD3, CD20, CD68) and used a low-density array to determine levels of T(H)1 (interleukin IL-2, IL-3, gamma-interferon, tumor necrosis factor-alpha, lymphotoxin-alpha, lymphotoxin-beta, granulocyte-macrophage colony-stimulating factor) and T(H)2 (IL-4, IL-5, IL-6, IL-10, and IL-13) transcripts as well as of IL-2R (as marker for T-cell activation) in 31 protocol biopsies of renal allografts. Here we show that grafts with early IF/TA and SCR can be distinguished from grafts with SCR on the basis of the activation of IL-10 gene expression and of an increased infiltration by B-lymphocytes in a cellular context in which the degree of T-cell activation is similar in both groups of biopsies, as demonstrated by equivalent levels of IL-2R mRNA. These results suggest that the up-regulation of the IL-10 gene expression, as well as an increased proportion of B-lymphocytes in the inflammatory infiltrates, might be useful as markers of early chronic lesions in grafts with SCR.
Hueso
Miguel
M
Departament de Nefrologia, Hospital Universitari de Bellvitge. IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain. mhueso@idibell.cat
Navarro
Estanis
E
Moreso
Francesc
F
O'Valle
Francisco
F
Pérez-Riba
Mercè
M
Del Moral
Raimundo García
RG
Grinyó
Josep M
JM
Serón
Daniel
D
D000328:Adult; D000368:Aged; D001284:Atrophy; D001706:Biopsy; D005260:Female; D005355:Fibrosis / Q000473:pathology*; D005786:Gene Expression Regulation; D006084:Graft Rejection; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D016030:Kidney Transplantation / Q000379:methods; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10