THU0247 LRRN4: A NOVEL PROGNOSTIC BIOMARKER OF RENAL OUTCOME IN LUPUS NEPHRITIS PATIENTS

Background:

Lupus nephritis (LN) is the most common organ-threatening manifestation of systemic lupus erythematosus (SLE) and can result in kidney deterioration and end-stage renal disease (ESRD). Newly discovered biomarkers exhibit qualities of disease activity and damage, predict long term preservation of renal function.

Objectives:

Combine the transcriptomics profile of kidney with long-term renal outcome in LN patients, to explore the novel non-invasive predictive biomarker for renal outcome.

Methods:

The transcriptomics profile of kidney in 24 LN patients was obtained by using Affymetrix human HTA 2.0 gene expression chip. Random Forest method was used to screen the candidate mRNA biomarkers by correlate the gene expression profile with eGFR slope during the follow-up (Mean time 5.2±1.2 years). In addition, in an independent LN cohort enrolled 45 patients, qRT-PCR and immunochemistry staining was performed to validate the correlation of mRNA level and protein level of candidate gene with renal outcome.

Results:

(1) There were 3212 gene was regulated in LN kidney (Fold change>1.5, FDA<0.05, compared with healthy control. DCBLD2, NPNT, CPVL, RGS5, LRRN4 were found to have the leading correlation with eGFR slope of LN patients by using random forest method. (2) In the independent cohort, we validate that the mRNA and protein level of DCBLD2, NPNT, CPVL, RGS5, LRRN4 was significantly evaluated in tubulointerstitial component in LN kidney, compared with healthy controls (p<0.05), and also significantly correlated with eGFR slope [LRRN4(r=-0.715, P<0.0001, DCBLD2(r=-0.620, P<0.0001, CPVL(r=-0.517, P=0.004, RGS5(r=-0.489, P=0.008, NPNT(r=-0.412, P=0.016]. In addition, the mRNA level of LRRN4 and DCBLD2 in kidney was correlated with SLEDAI score(r=0.611and r=0.512, respectively, P<0.001 and serum C3 level (r=0.501, r=0.435, P<0.05). LRRN4 mRNA level also significantly associated with tubulointerstitial fibrosis scoring(r=0.432, P<0.05;(3 he protein of LRRN4 was expressed both in glomeruli and tubulointerstitial tissue. And IHC level of LRRN4 protien was significantly associated with eGFR slope(r=0.534, P<0.05 in LN patients.

Conclusion:

LRRN4 in kidney may be used as a novel predictive biomarker of renal outcome in LN patients.

References:

[1]  Dall'Era M, Cisternas MG, Smilek DE, et al. Predictors of long-term renal outcome in lupus nephritis trials: lessons learned from the Euro-Lupus Nephritis cohort. Arthritis Rheumatol. 2015 May; 67(5):1305-13. [2] Misra R, Gupta R. Biomarkers in lupus nephritis. Int J Rheum Dis. 2015 Feb; 18(2):219-32.

Disclosure of Interests:

None declared