title: Aristolochic acid nephropathy revisited: a place for innate and adaptive immunity?
abstract: OBJECTIVE
  The histological features of aristolochic acid nephropathy (AAN) consist of paucicellular interstitial fibrosis, severe tubular atrophy, and almost intact glomeruli with media lesions of interlobular arteries. As an early phase of interstitial inflammation preceded peritubular fibrosis in the rat model of AAN, the aim was to investigate the presence of inflammatory cells in human AAN.
  
  
  RESULTS
  Reports of confirmed cases and case series of AAN were reviewed in terms of interstitial inflammation and found to have very conflicting results. This prompted us to search for and characterize inflammatory cells within the native kidneys provided from four end-stage AAN patients. Prior aristolochic acid exposure was attested by the intrarenal presence of the typical aristolactam I-derived DNA adduct. Besides the tubulointerstitial lesions usually seen in the cortex, a massive infiltration of macrophages, T and B lymphocytes was detected by immunohistochemistry in the medullary rays and in the outer medullae with some extension to the upper cortical labyrinth.
  
  
  CONCLUSIONS
  In parallel with histological findings reported in the rat model, inflammatory cells are present preferentially in the interstitium of the medullary rays and of the outer medulllae in renal interstitium from human AAN cases, even in the terminal stages. Further studies must be undertaken to determine the respective roles of innate and adaptive immunity in the progression of AAN.
authors.affiliation: Unit of Experimental Nephrology, Faculty of Medicine, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Agnieszka A
authors.initials: AA
authors.lastname: Pozdzik
authors.forename: Alix
authors.initials: A
authors.lastname: Berton
authors.forename: Heinz H
authors.initials: HH
authors.lastname: Schmeiser
authors.forename: Wassim
authors.initials: W
authors.lastname: Missoum
authors.forename: Christine
authors.initials: C
authors.lastname: Decaestecker
authors.forename: Isabelle J
authors.initials: IJ
authors.lastname: Salmon
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vanherweghem
authors.forename: Joëlle L
authors.initials: JL
authors.lastname: Nortier
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D000368:Aged; D034341:Aristolochic Acids / Q000009:adverse effects*; D016022:Case-Control Studies; D018450:Disease Progression; D004365:Drugs, Chinese Herbal / Q000009:adverse effects*; D005355:Fibrosis / Q000276:immunology / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009393:Nephritis / Q000139:chemically induced* / Q000473:pathology*
chemical_list: D034341:Aristolochic Acids; D004365:Drugs, Chinese Herbal; C000228:aristolochic acid I