title: Autoantibody profiling on human proteome microarray for biomarker discovery in cerebrospinal fluid and sera of neuropsychiatric lupus.
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.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
authors.forename: Chaojun
authors.initials: C
authors.lastname: Hu
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shan
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
authors.forename: Fengchun
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
authors.forename: Yongzhe
authors.initials: Y
authors.lastname: Li
mesh_terms: D001324:Autoantigens / Q000097:blood* / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D020945:Lupus Vasculitis, Central Nervous System / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D011379:Prognosis; D040081:Protein Array Analysis; D020543:Proteome
chemical_list: D001324:Autoantigens; D015415:Biomarkers; D020543:Proteome