Background/Purpose:

Given that early detection of renal involvement in systemic lupus erythematosus (SLE) and prompt management of the disease can have a significant impact on disease outcome, accurate diagnosis of lupus nephritis (LN) becomes absolutely critical. The current gold standard is to perform a renal biopsy in order to assess renal pathology. However, this procedure cannot be repeated serially, and is associated with untoward side-effects. Hence, there is an urgent need to identify biomarkers of LN that enable early detection of this disease.

Methods:

We have used serum samples from 22 SLE patients and matched healthy controls to hybridize to antibody-coated glass slide arrays that interrogated the level of 274 human proteins. Based on these screens, promising markers were further validated using single ELISA assays in independent cohorts of serum samples from lupus patients.

Results:

Whereas AXL, ferritin and sTNFRII were significantly elevated in patients with active LN relative to SLE patients who were quiescent, other molecules such as OPN, sTNFRI, sTNFRII, IGFBP2, SIGLEC5, FAS and MMP10 exhibited the capacity to distinguish SLE from healthy controls with ROC AUC exceeding 90%, all with p<0.001 significance.

These serum markers were next tested in a cohort of 45 LN patients where serum was obtained at the time of renal biopsy. In these patients, sTNFRII exhibited the strongest correlation with eGFR (r=0.50, p=0.0014) and serum creatinine (r=0.57, p=0.0001), though AXL, FAS, and IGFBP2 were also correlated with these clinical measures of concurrent nephritis. When concurrent renal biopsies from these patients were examined, serum FAS, IGFBP2 and TNFRII showed significant positive correlations with renal pathology activity index , while sTNFRII displayed the highest correlation with concurrently scored renal pathology chronicity index (r=0.57, p=0.001).

Finally, in a longitudinal cohort of 7 SLE patients examined at ~3-monthly intervals, AXL, ICAM-1, IGFBP2, SIGLEC5, sTNFRII and VCAM1 demonstrated the ability to track with concurrent disease flare, with significant subject to subject variation. To sum,

Conclusion:

Collectively, these studies suggest that serum levels of AXL, FAS, ferritin, ICAM-1, IGFBP2, SIGLEC-5 and sTNFRII are potential indicators of active LN and/or concurrent renal pathology indices or disease flares, worthy of further validation studies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/antibody-array-based-proteomic-screening-of-274-serum-markers-in-systemic-lupus-erythematosus/