Antibody-Array-Based Proteomic Screening of Serum Markers in Systemic Lupus Erythematosus: A Discovery Study

Tianfu Wu, Huihua Ding, Jie Han, Cristina Arriens, Chungwen Wei, Weilu Han, Claudia Pedroza, Shan Jiang, Jennifer Anolik, Michelle Petri, Ignacio Sanz, Ramesh Saxena, Chandra Mohan

Research output: Contribution to journalArticle

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Abstract

A discovery study was carried out where serum samples from 22 systemic lupus erythematosus (SLE) patients and matched healthy controls were hybridized to antibody-coated glass slide arrays that interrogated the level of 274 human proteins. On the basis of these screens, 48 proteins were selected for ELISA-based validation in an independent cohort of 28 SLE patients. Whereas AXL, ferritin, and sTNFRII were significantly elevated in patients with active lupus nephritis (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), although AXL, FAS, and IGFBP2 also correlated with these clinical measures of renal function. 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 seven SLE patients examined at 3 month intervals, AXL, ICAM-1, IGFBP2, SIGLEC5, sTNFRII, and VCAM-1 demonstrated the ability to track with concurrent disease flare, with significant subject to subject variation. In summary, serum proteins have the capacity to identify patients with active nephritis, flares, and renal pathology activity or chronicity changes, although larger longitudinal cohort studies are warranted.

Original languageEnglish (US)
Pages (from-to)2102-2114
Number of pages13
JournalJournal of Proteome Research
Volume15
Issue number7
DOIs
StatePublished - Jul 1 2016

Fingerprint

Pathology
Systemic Lupus Erythematosus
Proteomics
Screening
Biopsy
Biomarkers
Antibodies
Kidney
Vascular Cell Adhesion Molecule-1
Intercellular Adhesion Molecule-1
Ferritins
Blood Proteins
Creatinine
Lupus Nephritis
Proteins
Serum
Glass
Molecules
Nephritis
Area Under Curve

Keywords

  • AXL
  • biomarkers
  • FAS
  • IGFBP2
  • nephritis
  • pathology
  • TNFRII

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Antibody-Array-Based Proteomic Screening of Serum Markers in Systemic Lupus Erythematosus : A Discovery Study. / Wu, Tianfu; Ding, Huihua; Han, Jie; Arriens, Cristina; Wei, Chungwen; Han, Weilu; Pedroza, Claudia; Jiang, Shan; Anolik, Jennifer; Petri, Michelle; Sanz, Ignacio; Saxena, Ramesh; Mohan, Chandra.

In: Journal of Proteome Research, Vol. 15, No. 7, 01.07.2016, p. 2102-2114.

Research output: Contribution to journalArticle

Wu, T, Ding, H, Han, J, Arriens, C, Wei, C, Han, W, Pedroza, C, Jiang, S, Anolik, J, Petri, M, Sanz, I, Saxena, R & Mohan, C 2016, 'Antibody-Array-Based Proteomic Screening of Serum Markers in Systemic Lupus Erythematosus: A Discovery Study', Journal of Proteome Research, vol. 15, no. 7, pp. 2102-2114. https://doi.org/10.1021/acs.jproteome.5b00905
Wu, Tianfu ; Ding, Huihua ; Han, Jie ; Arriens, Cristina ; Wei, Chungwen ; Han, Weilu ; Pedroza, Claudia ; Jiang, Shan ; Anolik, Jennifer ; Petri, Michelle ; Sanz, Ignacio ; Saxena, Ramesh ; Mohan, Chandra. / Antibody-Array-Based Proteomic Screening of Serum Markers in Systemic Lupus Erythematosus : A Discovery Study. In: Journal of Proteome Research. 2016 ; Vol. 15, No. 7. pp. 2102-2114.
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abstract = "A discovery study was carried out where serum samples from 22 systemic lupus erythematosus (SLE) patients and matched healthy controls were hybridized to antibody-coated glass slide arrays that interrogated the level of 274 human proteins. On the basis of these screens, 48 proteins were selected for ELISA-based validation in an independent cohort of 28 SLE patients. Whereas AXL, ferritin, and sTNFRII were significantly elevated in patients with active lupus nephritis (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), although AXL, FAS, and IGFBP2 also correlated with these clinical measures of renal function. 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 seven SLE patients examined at 3 month intervals, AXL, ICAM-1, IGFBP2, SIGLEC5, sTNFRII, and VCAM-1 demonstrated the ability to track with concurrent disease flare, with significant subject to subject variation. In summary, serum proteins have the capacity to identify patients with active nephritis, flares, and renal pathology activity or chronicity changes, although larger longitudinal cohort studies are warranted.",
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