Background/Purpose: Lupus nephritis (LN) is one of the most serious complications of Systemic lupus erythematosus (SLE). Early diagnosis of renal impairment, combined with a strict follow-up of patients, is important to avoid morbidity and mortality. Yet, current conventional biomarkers (proteinuria, urinary protein/creatinine ratio, estimated glomerular filtration rate, serum anti-dsDNA antibody titers, serum complement levels) reflect systemic rather than renal activity of the disease, or, in the case of proteinuria, remain elevated as a consequence of chronic damage. The aim of this study was to identify new biomarkers reflecting intra-renal activation of immune cells and renal tubular cell damage, the main determinants of impaired renal function in LN.

Methods: Using transcriptomic data generated in LN versus control renal biopsies in the context of the PRECISESADS study, we identified candidate biomarkers that correlated with intra-renal infiltration by immune effectors or histological evidence of tubular damage, and were potentially secreted in the serum: IL34, MMP7, RANTES, SLA2, CXCL12, CCL19 and CCL21. We evaluated concentrations of these eight biomarkers in sixty-seven LN and in eight control sera. IL34, MMP7, RANTES and SLA2 were evaluated by ELISA and CXCL12, CCL19 and CCL21 using a Bioplex assay. Biological indices of disease activity were retrieved from the patients files.

Results: Serum IL34 (p value: 0.0288), MMP7, CXCL12, CCL19 and CCL21 (p values: <0.0001) concentrations were significantly higher in LN patients than in controls. Strikingly, serum MMP7 and CXCL12 concentrations were negatively correlated with eGFR (p values: 0.0135 and 0.0190 respectively), while this was not the case for anti-dsDNA antibody titers, serum C3 or urinary protein/creatinine ratio. Accordingly, serum MMP7 and CXCL12 concentrations were significantly higher in patients with an eGFR < 50 mL/min/1.73 m² compared to > 50 mL/min/1.73 m² (p values: 0.0020 and 0.0336, respectively).

Conclusion: Adequate management of LN will be served by the identification of biomarkers reflecting intra-renal rather than systemic inflammation. By opposition to conventional biomarkers, MMP7 and CXCL12, which are produced in the kidney itself, displayed a significant negative correlation with eGFR in LN. Confirmation of these results in independent cohorts of samples is pending.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mmp7-and-cxcl12-two-promising-biomarkers-in-lupus-nephritis/