Simple lectin blood test could help detect and track lupus nephritis without costly mass spectrometry

Between 40% and 60% of people with systemic lupus erythematosus (SLE) develop lupus nephritis (LN), a leading cause of illness and death in lupus. LN is confirmed by kidney biopsy, which is invasive and hard to repeat for monitoring. Standard blood markers such as anti-dsDNA antibodies and complement levels lack sensitivity and specificity. Earlier work found that the sugar chains on the Fc region of IgG (at Asn297) change in lupus, with less galactose and sialic acid favouring pro-inflammatory activity. Measuring these sugars has relied on mass spectrometry, which is expensive, complex and impractical for routine labs.

The Tulane-led team built a lectin-based enzyme-linked assay to measure IgG glycans. Plates were coated with protein L, which captures IgG through its light chain and leaves the Fc glycans accessible. Purified IgG from standards or patient plasma was added, then biotinylated lectins: Aleuria aurantia lectin (AAL) for fucose, Erythrina cristagalli lectin (ECL) for galactose, and Sambucus nigra lectin (SNA) for α2,6-linked sialic acid. Signal was developed with streptavidin-HRP and TMB and read at 450 nm. The team tuned blocking solutions, lectin concentrations and IgG standard ranges (up to 20 µg/mL).

Standard 5% BSA caused glycan-related cross-reactivity with AAL and SNA, so deglycosylated BSA or a carbohydrate-free blocking solution was needed. ECL tolerated all blockers. Optimised standard-curve ranges were 0–4 µg/mL for AAL, 0–20 µg/mL for ECL and 0–2 µg/mL for SNA, with R² above 0.98. In IgG from one healthy donor and one LN patient, readings fell within the standard ranges. The patient sample showed lower AAL (0.108 vs 0.421 µg/mL equivalents) and lower ECL binding (0.367 vs 0.514), consistent with mass spectrometry findings.

The clinical cohort was 30 children with SLE from a single Houston centre (2015–2021). Disease activity was scored by SLEDAI-2000 and renal SLEDAI, and LN was biopsy-confirmed. Per the abstract, there were four groups: active LN, active non-renal SLE, quiescent SLE, and LN after 6 months of immunosuppression. Fucose (AAL) binding did not differ among subgroups. Galactose (ECL) binding was significantly different in active LN compared with both active non-renal SLE and quiescent disease. Sialic acid (SNA) binding separated active LN from quiescent SLE but not renal from non-renal SLE.

If validated, an ECL-based ELISA could be a practical, lower-cost way to help diagnose LN and follow disease activity, using equipment most clinical labs already have. Important caveats apply. The cohort is small and pediatric, from one centre, and the healthy-versus-LN comparison used single samples. The assay has not been tested for diagnostic accuracy (sensitivity, specificity, cutoffs), reproducibility across labs, or performance in adults. The supplied text was truncated before the detailed cohort tables and statistics, so subgroup findings here follow the abstract.