Mast cells and tubulointerstitial fibrosis in patients with ANCA-associated glomerulonephritis.
BACKGROUND
To elucidate the role of mast cells (MCs) in the pathogenesis of crescentic glomerulonephritis, we investigated the immunohistochemical localization of MCs in the kidney and the correlation between MC localization and tubulointerstitial lesions in biopsy specimens and serum stem cell factor (SCF) levels in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis.


METHODS
Thirteen patients with ANCA-associated glomerulonephritis were enrolled in this study. Clinical parameters, such as serum creatinine and urinary protein excretion, were obtained from each patient at the time of biopsy. Paraffin-embedded sections were used for immunohistochemical staining, using the labelled streptavidin bio-tin (LSAB) method. Monoclonal antibodies to human tryptase, alpha-smooth-muscle actin, and CD68 were used as primary antibodies. Ten cortical interstitial fields were randomly selected at an original magnification of x400 and assessed using a computer-assisted color image analyzer. Tubulointerstitial fibrosis was assessed as the percentage of the area stained with Masson trichrome in ten cortical interstitial fields. The measurement of serum SCF levels was performed by using an enzyme-linked immunoassay.


RESULTS
In all of the control subjects, a few tryptase-positive MCs were observed in the glomeruli and interstitium. In contrast, sparse MCs were observed in the interstitium, but not in the glomeruli of diseased kidneys. The number of interstitial MCs in the tubulointerstitial lesions was positively correlated with the degree of interstitial fibrosis. Moreover, a significant positive correlation was observed between the number of interstitial MCs and the serum SCF concentration (r = 0.85; P = 0.001).


CONCLUSIONS
Our findings suggest that MC infiltration induced by SCF in interstitial tissues seems to be associated with tubulointerstitial fibrosis in human ANCA-associated glomerulonephritis.
Otsubo
Shigeru
S
Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. shigeyuri@nifty.com
Nitta
Kosaku
K
Uchida
Keiko
K
Yumura
Wako
W
Nihei
Hiroshi
H
D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology* / Q000473:pathology; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000473:pathology*; D008875:Middle Aged; D012189:Retrospective Studies; D019089:Stem Cell Factor / Q000097:blood; D000097382:CD68 Molecule
D019268:Antibodies, Antineutrophil Cytoplasmic; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003404:Creatinine; D019089:Stem Cell Factor; C067980:CD68 antigen, human; D000097382:CD68 Molecule