Autoantibody profiling on human proteome microarray for biomarker discovery in cerebrospinal fluid and sera of neuropsychiatric lupus

PLoS One. 2015 May 8;10(5):e0126643. doi: 10.1371/journal.pone.0126643. eCollection 2015.

Abstract

Autoantibodies in cerebrospinal fluid (CSF) from patients with neuropsychiatric systemic lupus erythematosus (NPSLE) may be potential biomarkers for prediction, diagnosis, or prognosis of NPSLE. We used a human proteome microarray with~17,000 unique full-length human proteins to investigate autoantibodies associated with NPSLE. Twenty-nine CSF specimens from 12 NPSLE, 7 non-NPSLE, and 10 control (non-systemic lupus erythematosus)patients were screened for NPSLE-associated autoantibodies with proteome microarrays. A focused autoantigen microarray of candidate NPSLE autoantigens was applied to profile a larger cohort of CSF with patient-matched sera. We identified 137 autoantigens associated with NPSLE. Ingenuity Pathway Analysis revealed that these autoantigens were enriched for functions involved in neurological diseases (score = 43).Anti-proliferating cell nuclear antigen (PCNA) was found in the CSF of NPSLE and non-NPSLE patients. The positive rates of 4 autoantibodies in CSF specimens were significantly different between the SLE (i.e., NPSLE and non-NPSLE) and control groups: anti-ribosomal protein RPLP0, anti-RPLP1, anti-RPLP2, and anti-TROVE2 (also known as anti-Ro/SS-A). The positive rate for anti-SS-A associated with NPSLE was higher than that for non-NPSLE (31.11% cf. 10.71%; P = 0.045).Further analysis showed that anti-SS-A in CSF specimens was related to neuropsychiatric syndromes of the central nervous system in SLE (P = 0.009). Analysis with Spearman's rank correlation coefficient indicated that the titers of anti-RPLP2 and anti-SS-A in paired CSF and serum specimens significantly correlated. Human proteome microarrays offer a powerful platform to discover novel autoantibodies in CSF samples. Anti-SS-A autoantibodies may be potential CSF markers for NPSLE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens / blood*
  • Autoantigens / cerebrospinal fluid*
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Humans
  • Lupus Vasculitis, Central Nervous System / blood*
  • Lupus Vasculitis, Central Nervous System / cerebrospinal fluid*
  • Lupus Vasculitis, Central Nervous System / diagnosis
  • Prognosis
  • Protein Array Analysis
  • Proteome

Substances

  • Autoantigens
  • Biomarkers
  • Proteome

Grant support

This work was supported by 2014BAI07B00 to Yongzhe Li, National Science Technology Pillar Program in the 12nd Five-year Plan, sponsoring materials; 201202004 to Fengchun Zhang, Research Special Fund for Public Welfare Industry of Health, sponsoring materials; 2011AA02A113 to Yongzhe Li, Chinese National High Technology Research and Development Program, Ministry of Science and Technology Grants, sponsoring materials; 81072486, 81373188, and 81172857 to Yongzhe Li, 81302610 to Chaojun Hu, 81302590 to Hua Chen, and 81172084 to Lin Wu, National Natural Science Foundation of China Grants, sponsoring data collection and analysis.