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.
Departament de Nefrologia, Hospital Universitari de Bellvitge. IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain. mhueso@idibell.cat
Miguel
M
Hueso
Estanis
E
Navarro
Francesc
F
Moreso
Francisco
F
O'Valle
Mercè
M
Pérez-Riba
Raimundo García
RG
Del Moral
Josep M
JM
Grinyó
Daniel
D
Serón
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