Various roles of Th cytokine mRNA expression in different forms of glomerulonephritis.
BACKGROUND
Kidney disease is characterized by injurious immune responses to self or foreign antigens. The development and maintenance of immune responses generally involves activation of T lymphocytes. We evaluated mRNA expression patterns of T-cell cytokines to identify the principal Th-cell subset involved in the development of antineutrophil cytoplasmic antigen-associated pauci-immune crescentic glomerulonephritis (ANCAGN), membranoproliferative glomerulonephritis (MPGN), and membranous nephropathy (MN).


METHODS
Kidney biopsy specimens from ANCAGN (17), MPGN (11), and MN (14) patients were evaluated for mRNA expression of various T-cell cytokines.


RESULTS
Interferon-γ mRNA expression was detected in both ANCAGN and MPGN, but not in MN patients. Furthermore, mRNA expression of interleukin (IL)-12, a Th1-associated cytokine, was lower in MN patients than in ANCAGN and MPGN patients. In contrast, a significantly higher expression of IL-4 and IL-5 was observed in MN than in ANCAGN and MPGN patients. In the analyses of Th17-associated cytokine expression, a significantly higher expression of IL-6 and IL-17 was observed in ANCAGN than in MPGN and MN patients. No significant differences were observed in the expression of these cytokines between MPGN and MN patients. With regard to Treg-associated cytokines, a significantly higher IL-10 expression was observed in MN than in ANCAGN patients, and a significantly higher transforming growth factor-β expression was observed in MN than in ANCAGN and MPGN patients. Similarly, Foxp3 expression was significantly higher in MN.


CONCLUSIONS
Th1 and Th17 immune responses in ANCAGN, the Th1 response in MPGN, and Th2 and Treg responses in MN patients may be integral for the distinct histological features of these diseases.
Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
Masakazu
M
Ifuku
Katsuhisa
K
Miyake
Maho
M
Watanebe
Kenji
K
Ito
Yasuhiro
Y
Abe
Yoshie
Y
Sasatomi
Satoru
S
Ogahara
Satoshi
S
Hisano
Hiroshi
H
Sato
Takao
T
Saito
Hitoshi
H
Nakashima
D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000378:metabolism; D001706:Biopsy; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism*; D015433:Glomerulonephritis, Membranous / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology*; D058504:Th17 Cells / Q000166:cytology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D016207:Cytokines; D015848:Interleukin-5; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma