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J Proteome Res. 2016 Jul 1;15(7):2102-14. doi: 10.1021/acs.jproteome.5b00905. Epub 2016 Jun 7.

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

Author information

1
Department Biomedical Engineering, University of Houston , Houston, Texas 77204, United States.
2
Division of Nephrology/Rheumatology, UT Southwestern Medical Center at Dallas , Dallas, Texas 75390, United States.
3
Division of Rheumatology, Emory University , Atlanta, Georgia 30322, United States.
4
Center for Clinical Research and Evidence-Based Medicine, University of Texas Health Science Center at Houston , Houston, Texas 77030, United States.
5
Division of Rheumatology, University of Rochester , Rochester, New York 14642, United States.
6
Division of Rheumatology, Johns Hopkins University Medical School , Baltimore, Mississippi 21205, United States.

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.

KEYWORDS:

AXL; FAS; IGFBP2; TNFRII; biomarkers; nephritis; pathology

PMID:
27211902
PMCID:
PMC5193538
DOI:
10.1021/acs.jproteome.5b00905
[Indexed for MEDLINE]
Free PMC Article

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