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.
Highlights
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by production of pathogenic autoantibodies and multiple organ and tissue damage[1]
Since the reproducibility of protein microarray data is crucial for biomarker identification, we first assessed their quality by probing a human proteome microarray, randomly selected from the same printing batch, with anti-GST monoclonal antibody (mAb)
To identify neuropsychiatric systemic lupus erythematosus (NPSLE)-specific Cerebrospinal fluid (CSF) autoantibodies, we profiled the autoimmune reactivity by incubating the human proteome microarrays with 29 individual CSF samples from 12 NPSLE, 7 non-NPSLE, and 10 non-SLE patients, and performed signal detection with Cy5-labeled anti-human immunoglobulin G (IgG) antibodies
Summary
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by production of pathogenic autoantibodies and multiple organ and tissue damage[1]. A variety of autoantibodies have been detected in the CSF of SLE patients, including anti-glutamate receptor ε2 subunit (GluRε2)[3], anti-neuronal[4], anti-ganglioside[5], anti-glial fibrillary acidic protein[6], anti-dsDNA, anti-N-methyl-d-aspartate (NMDA) receptors[7], anti-triose-phosphateisomerase[8], anti-SSA/Ro (Anti-Sjögren’s-syndrome-related antigen A, or anti-Ro)[9], anti-ribosomal P protein[10], anti-cardiolipin[11], and anti-alphainternexin autoantibodies[12] Most of these autoantibodies can be detected in other autoimmune diseases; only a small fraction of them (such as anti-GluRε2 and antiNMDA)are associated with neuropsychiatric disorders[3, 7]. Based on the current literature, we hypothesized that there are additional autoantibodies in CSF that can be used to diagnose or predict NPSLE
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