Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus.
OBJECTIVE
To study 5 type I interferon (IFN)-inducible genes (LY6E, OAS1, OASL, MX1, and ISG15) in patients with systemic lupus erythematosus (SLE) and to correlate expression levels with disease activity and/or clinical manifestations.


METHODS
Peripheral blood cells were obtained from 48 SLE patients, 48 normal controls, and 22 rheumatic disease controls, and total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by real-time polymerase chain reaction, standardized to a housekeeping gene, and summed to an IFN score. Disease activity was determined by the Safety of Estrogens in Lupus Erythematosus: National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) composite.


RESULTS
Each gene was highly expressed in SLE patients compared with normal controls (P < or = 0.0003) or disease controls (P < or = 0.0008 except for MX1). IFN scores were positively associated with the SELENA-SLEDAI instrument score (P = 0.001), the SELENA-SLEDAI flare score (P = 0.03), and the physician's global assessment score (P = 0.005). Compared with patients without nephritis, lupus nephritis patients had higher IFN scores (overall P < 0.0001), especially during active renal disease. IFN scores were weakly associated with neurologic manifestations. Elevated IFN scores were positively associated with the current presence of anti-double-stranded DNA (anti-dsDNA) antibodies (P = 0.007) or hypocomplementemia (P = 0.007). LY6E expression levels distinguished active from inactive lupus nephritis (P = 0.02) and were positively associated with proteinuria (P = 0.009).


CONCLUSIONS
The 5 IFN-inducible genes were highly expressed in SLE patients, and increased levels were correlated with disease activity defined by several methods. IFN scores, or LY6E levels, were elevated in lupus nephritis patients, especially during active renal disease, and in patients with anti-dsDNA antibody positivity and hypocomplementemia. IFN scores, or LY6E levels, may be useful as a biomarker for lupus nephritis therapy.
Feng
Xuebing
X
David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1670, USA.
Wu
Hui
H
Grossman
Jennifer M
JM
Hanvivadhanakul
Punchong
P
FitzGerald
John D
JD
Park
Grace S
GS
Dong
Xin
X
Chen
Weiling
W
Kim
Michelle H
MH
Weng
Haoling H
HH
Furst
Daniel E
DE
Gorn
Alan
A
McMahon
Maureen
M
Taylor
Mihaela
M
Brahn
Ernest
E
Hahn
Bevra H
BH
Tsao
Betty P
BP
D000328:Adult; D000368:Aged; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000503:physiopathology; D008181:Lupus Nephritis / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D012016:Reference Values; D012216:Rheumatic Diseases / Q000235:genetics / Q000503:physiopathology
D012313:RNA