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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Lupus+Sci+Med
2015 ; 2
(1
): e000112
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Characterising the immune profile of the kidney biopsy at lupus nephritis flare
differentiates early treatment responders from non-responders
#MMPMID26629350
Parikh SV
; Malvar A
; Song H
; Alberton V
; Lococo B
; Vance J
; Zhang J
; Yu L
; Rovin BH
Lupus Sci Med
2015[]; 2
(1
): e000112
PMID26629350
show ga
INTRODUCTION: The kidney biopsy is used to diagnose and guide initial therapy in
patients with lupus nephritis (LN). Kidney histology does not correlate well with
clinical measurements of kidney injury or predict how patients will respond to
standard-of-care immunosuppression. We postulated that the gene expression
profile of kidney tissue at the time of biopsy may differentiate patients who
will from those who will not respond to treatment. METHODS: The expression of 511
immune-response genes was measured in kidney biopsies from 19 patients with
proliferative LN and 4 normal controls. RNA was extracted from formalin-fixed,
paraffin-embedded kidney biopsies done at flare. After induction therapy, 5
patients achieved a complete clinical response (CR), 10 had a partial response
(PR) and 4 patients were non-responders (NRs). Transcript expression was compared
with normal controls and between renal response groups. RESULTS: A principal
component analysis showed that intrarenal transcript expression from normal
kidney, CR biopsies and NR biopsies segregated from each other. The top genes
responsible for CR clustering included several interferon pathway genes (STAT1,
IRF1, IRF7, MX1, STAT2, JAK2), while complement genes (C1R, C1QB, C6, C9, C5,
MASP2) were mainly responsible for NR clustering. Overall, 35 genes were uniquely
expressed in NR compared with CR. Pathway analysis revealed that interferon
signalling and complement activation pathways were upregulated in both groups,
while BAFF, APRIL, nuclear factor-?B and interleukin-6 signalling were increased
in CR but suppressed in NR. CONCLUSIONS: These data suggest that molecular
profiling of the kidney biopsy at LN flare may be useful in predicting treatment
response to induction therapy.
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