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SUMMARY: DISCOVERY AND QUALIFICATION OF CANDIDATE URINARY BIOMARKERS OF DI
 SEASE ACTIVITY IN LUPUS NEPHRITIS  - Dr. Veronica Anania from Genentech\, 
 South San Francisco\, CA\, USA
DTSTART:20180227T141500Z
DTEND:20180227T151500Z
UID:TALK101899@talks.cam.ac.uk
CONTACT:6290
DESCRIPTION:Lupus nephritis (LN) is a severe clinical manifestation of sys
 temic lupuserythematosus (SLE) associated with significant morbidity and m
 ortality.Assessment of severity and activity of renal involvement in SLE r
 equiresa kidney biopsy\, an invasive procedure with limited prognostic val
 ue. A need remains for non-invasive biomarkers to help inform treatment de
 cisions and to monitor disease activity and progression. Proteinuria\, or 
 high levels of protein in urine\, is associated with disease progression i
 n LN\,however\, the composition of the urinary proteome of LN patients rem
 ains incompletely characterized. To better understand the urinary LN prote
 ome\,we performed a proteomics study to identify urinary biomarkers of LN.
  Urine samples from three patients with biopsy-confirmed LN and high prote
 inuria (>3 mg/mmol)\, and low serum complement C3 (<80 mg/dL) were compare
 d to three age and gender matched healthy controls (HC). These samples wer
 eprofiled using three complementary mass spectrometry based methods: SDS-P
 AGE gel fractionation\, a chemical labelling approach using tandem mass ta
 gs (TMT)\, and a label free data-independent acquisition (DIA) method.\nCo
 mbining results from both TMT and DIA analyses yielded quantitative inform
 ation on 2\,573 unique proteins in urine from LN patients. In total\, 496 
 proteins were significantly up-regulated in LN samples compared to HC by a
 t least one method\, and 41 proteins were found to be significantly up-reg
 ulated in LN urine compared to HC by both TMT and DIA approaches (p-value 
 <0.05). A multiple reaction monitoring (MRM) method was established to val
 idate eight of the proteins in an independent cohort of LN patients\,and s
 even proteins (transferrin\, alpha-2-macroglobulin\, haptoglobin\, afamin\
 , alpha-1-antitrypsin\, vimentin\, and ceruloplasmin) were confirmed to be
  elevated in LN urine compared to HC. In this study\, we demonstrate that 
 mass spectrometry analysis of urine from a small number of LN patient samp
 les can identify high quality candidate biomarkers that replicate in an in
 dependent LN disease cohort. These biomarkers are being used to inform cli
 nical biomarker strategies to support longitudinal and interventional stud
 ies focused on evaluating disease progression and treatment efficacy of LN
  therapeutics.\n
LOCATION:Department of Biochemistry\, Sanger Building Jean Thomas Lecture 
 Theatre
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