Identify biomarkers of neuropsychiatric systemic lupus erythematosus by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry combined with weak cation magnetic beads.
OBJECTIVE
To identify proteomic biomarkers in cerebrospinal fluid (CSF) and develop a diagnostic proteomic model for neuropsychiatric systemic lupus erythematosus (NPSLE).


METHODS
CSF proteomic spectra were generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) combined with weak cation exchange (WCX) magnetic beads. The spectra were taken from 27 patients with NPSLE before and after treatment, and 27 controls including 17 patients with scoliosis and 10 patients with SLE but without neuropsychiatric manifestation. Discriminating peaks were processed by Biomarker Patterns Software to build a decision tree model for NPSLE classification. In addition, CSF samples of 12 patients with NPSLE, 12 patients with lumbar disc herniation, and 9 patients with other neurological conditions were used as a blind test group to verify the accuracy of the model.


RESULTS
Twelve discriminating mass-to-charge (m/z) peaks were identified between NPSLE and controls: m/z peaks 7740, 11962, 8065, 7661, 6637, 5978, 11384, 11744, 8595, 10848, 7170, and 5806. The diagnostic decision tree model, built with a panel of m/z peaks 8595, 7170, 7661, 7740, and 5806, recognized NPSLE with both sensitivity and specificity of 92.6%, based on training group samples, and sensitivity and specificity of 91.7% and 85.7%, respectively, based on the blind test group. In addition, the root node m/z peak 8595 protein, which was downregulated in the CSF of patients with NPSLE after treatment, was identified and confirmed as ubiquitin by immunoprecipitation and ELISA.


CONCLUSIONS
Potential CSF biomarkers for NPSLE are identified by MALDI-TOF-MS combined with WCX magnetic beads. The novel diagnostic proteomic model with m/z peaks 8595, 7170, 7661, 7740, and 5806 is highly sensitive and relatively specific for NPSLE diagnosis. The level of ubiquitin in CSF is a promising biomarker for active NPSLE.
Department of Rheumatology, Chinese Academy of Medical Science, Beijing 100005, China.
Ling
L
Sun
Hua
H
Chen
Chaojun
C
Hu
Peng
P
Wang
Yongzhe
Y
Li
Jing
J
Xie
Fulin
F
Tang
Denian
D
Ba
Xuan
X
Zhang
Wei
W
He
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002412:Cations; D005260:Female; D006801:Humans; D018189:Immunomagnetic Separation / Q000379:methods*; D020945:Lupus Vasculitis, Central Nervous System / Q000134:cerebrospinal fluid* / Q000145:classification / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000032:analysis*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D055815:Young Adult
D015415:Biomarkers; D002412:Cations; D020543:Proteome