Relationship of intrarenal gene expression and the histological class of lupus nephritis -- a study on repeat renal biopsy.
OBJECTIVE
To study the role of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK)/Fn14 and the interferon-inducible protein (IP-10)/CXCR3 axis in lupus nephritis (LN).


METHODS
We studied 113 patients with LN who had had repeat renal biopsies. Glomerular and tubulointerstitial messenger RNA expression of TWEAK, Fn14, IP-10, and CXCR3 were quantified.


RESULTS
Glomerular Fn14 expression decreased when changed from proliferative or mixed nephritis to membranous nephropathy (p = 0.016), and increased when changed from membranous to proliferative or mixed nephritis (p = 0.0006). On the other hand, tubulointerstitial TWEAK expression decreased when changed from proliferative or mixed nephritis to membranous nephropathy (p = 0.004), and increased when changed from membranous nephropathy to proliferative nephritis (p = 0.010). Tubulointerstitial IP-10 expression decreased when changed from proliferative or mixed nephritis to membranous nephropathy (p < 0.0001). Histological activity index correlated significantly with the glomerular expression of Fn14 (r = 0.421, p < 0.0001) and tubulointerstitial expression of TWEAK (r = 0.413, p < 0.0001) and IP-10 (r = 0.472, p < 0.0001).


CONCLUSIONS
Glomerular Fn14 and tubulointerstitial TWEAK and IP-10 expression appeared to have consistent changes in relation to the histological class of LN and correlated with the histological activity index. Our findings suggest a specific role of these genes in the pathogenesis of LN.
Department of Medicine and Therapeutics and the Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong (CUHK), Shatin, Hong Kong, China.
Jianxin
J
Lu
Cheuk-Chun
CC
Szeto
Lai-Shan
LS
Tam
Fernand Mac-Moune
FM
Lai
Edmund Kwok-Ming
EK
Li
Kai-Ming
KM
Chow
Philip Kam-Tao
PK
Li
Bonnie Ching-Ha
BC
Kwan
D000293:Adolescent; D000328:Adult; D054357:Chemokine CXCL10 / Q000235:genetics* / Q000378:metabolism; D000074049:Cytokine TWEAK; D005260:Female; D015870:Gene Expression; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D008181:Lupus Nephritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D054367:Receptors, CXCR3 / Q000235:genetics* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors / Q000235:genetics* / Q000378:metabolism
C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D000074049:Cytokine TWEAK; D054367:Receptors, CXCR3; D018124:Receptors, Tumor Necrosis Factor; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors