Data from a cross-sectional pilot study published in Rheumatology indicate that the glycoprotein α1-antichymotrypsin (SERPINA3) may be an effective urinary biomarker for lupus nephritis (LN) activity.
Investigators assembled a discovery cohort (n=20) from an ongoing pediatric lupus study at the Cincinnati Children’s Hospital Medical Center in Ohio. Bio-banked urine samples collected within a month of kidney biopsy were used for subsequent proteomic analyses. Urine peptides were isolated and tagged with isobaric tags for relative and absolute quantification (iTRAQ) to identify candidate urine biomarkers (CUBMs). Overall, iTRAQ detected 112 proteins from the urine samples of the discovery cohort, 51 of which were quantifiable in all subsequent technical replicates. According to cumulative iTRAQ results and heat-map analyses, the 7 best-performing CUBMs were selected for quantification in the urine samples of a validation cohort (n=41). CUBM levels were determined using enzyme-linked immunosorbent assays and investigated for association with LN chronicity.
The best-performing CUBMs included afamin (AFM), retinol binding protein 4 (RBP4), α1-acid glycoprotein 1 (ORM1), immunoglobulin heavy constant α 1 (IGHA1), transthyretin (TTR), and SERPINA3. After adjustment for LN activity, none of the candidate CUBMs were found to differ based on degree of LN chronicity. Degree of LN chronicity was associated with renal Systemic Lupus Erythematosus Disease Activity Index and with creatinine clearance, but not with protein creatinine ratio.
A mild positive association was identified between National Institutes of Health (NIH) Chronicity Index scores and the biomarkers TF (P =.037), TTR (P =.17), ORM1 (P =.07), and SERPINA3 (P =.13). SERPINA3 specifically was found to have a moderate positive association with NIH Activity Index scores (P =.005) and a significant correlation with histologic LN activity (P =.03). Immunohistochemistry of LN biopsies indicated that SERPINA3 expression was localized to endothelial cells and proximal tubular epithelial cells. TF (P =.003) and ORM1 (P =.005) were also moderately positively associated with NIH Activity Index scores. Strong positive associations were detected between SERPINA3 and TF, ORM1, and AFM (P <.0001).
According to proteomics analyses, SERPINA3 emerged as the most promising urine biomarker for LN chronicity. Additional research is needed to assess the applicability of SERPINA3 in clinical treatment and its role in pathogenesis.
Turnier JL, Brunner HI, Bennett M, et al. Discovery of SERPINA3 as a candidate urinary biomarker of lupus nephritis activity [published online October 04, 2018]. Rheumatology. doi:10.1093/rheumatology/key301