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Objectives We used a high-throughput multiplex assay to identify candidate plasma biomarkers for active renal disease and for renal response to rituximab in patients with SLE.Methods Participants recruited to the UK prospective observational study, the British Isles Lupus Assessment Group Biologics Register (BILAG-BR) were included if they had active disease and a plasma sample available prior to treatment with rituximab. Active disease was defined by > 1 BILAG A or two B scores in any domain and renal response was considered as an improvement in the renal BILAG domain from A or B at baseline, to a C or D at follow-up. Healthy controls (HCs) were included from the Lupus Extended Autoimmune Phenotype (LEAP) study.The NULISA™ assay was used to quantify 250 plasma proteins. The log2-fold change of proteins was compared between groups and a false discovery rate (FDR) adjustment for multiple testing was applied. Logistic regression was used to assess the strength of individual protein association with renal response at six and 12 months in models adjusted for age, sex and ancestry.Results In 250 individuals with SLE and 14 HCs, there were 156 differentially expressed proteins between the two groups. Of those with SLE, 113/250 (45%) had active renal disease at baseline, and these individuals were younger (p=0.014) and were more likely to be of Asian ancestry (p=0.015). Active renal disease was associated with a higher expression of 51 proteins compared to those with active non-renal disease at baseline. Of those with active renal disease, renal response was achieved in 54/92 (59%) and 44/80 (55%) at six and 12 months. Proteins identified as being associated with response at both time-points, included hepatitis A virus cellular receptor 1 (HAVCR-1), a co-stimulatory protein, also known as kidney injury molecule, and tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) a regulator of type IV collagen digestion and a urinary marker of acute kidney injury.Conclusions We identified proteins known to associate with acute kidney injury which have not previously been associated with lupus nephritis; these may predict renal response to rituximab treatment.