Session Information
Date: Tuesday, November 7, 2017
Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis Poster II
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose:
Systemic lupus erythematosus (SLE), an autoimmune disorder characterized by the production of pathogenic autoantibodies and inflammatory mediators, involves multiple organ systems. Neuropsychiatric systemic lupus erythematosus (NPSLE) is often difficult to diagnose and distinguish from other diseases, partly because no NPSLE-specific antibodies have been identified.Suprabasin (SBSN) gene was originally identified in mouse and human differentiating keratinocytes as an epidermal differentiation marker. SBSN also plays a role in the growth and invasiveness of tumors. It was demonstrated that the knockdown of SBSN inhibited cell migration and tube formation in tumor endothelial cells, but the pathological role of SBSN in autoimmune disease is not well understood.
Methods:
We developed a novel proteomic strategy for identifying and profiling antigens in immune complexes (ICs) in the cerebrospinal fluid (CSF), and we used this strategy for 26 NPSLE patients. As controls, 25 SLE patients without neuropsychiatric manifestations (SLE), 15 with relapsing remitting multiple sclerosis (RRMS) and 10 normal pressure hydrocephalus (NPH) patients were included. We analyzed the titer of anti-SBSN antibodies in CSF, using a luciferase immunoprecipitation system (LIPS) assay. Real-time quantitative polymerase chain reaction (qPCR) and microarray analysis following exposure of astrocytes to anti-SBSN antibodies were performed. We also performed a multiplex cytokine bead assay using undiluted CSF supernatants and the Bio-Plex Pro Human Cytokine Group I 27-Plex Panel analyzed with a Bio-Plex® MAGPIX™ Multiplex Reader.
Results:
We identified ICs of SBSN in the CSF of the NPSLE group. We also analyzed the CSF of a total of 103 patients (NPSLE=31, SLE=22, MS=30 and NPH=20) from another cohort for anti-SBSN antibodies, using a luciferase immunoprecipitation system (LIPS) assay. The LIPS assay showed that the CSF an antibody index (A.I.) of anti-SBSN antibodies was significantly higher in the NPSLE group compared to the A.I. values of the SLE, MS and NPH groups. Among them, the CSF of 41.9% (13 of 31) NPSLE patients was positive for anti-SBSN antibodies. Of note, the CSF concentrations of IL-10, IL-13, GM-CSF, IP-10 and MCP-1 were significantly higher in the CSF anti-SBSN antibodies-positive group of NPSLE patients compared to those of the negative group. The expression of SERPINE1 mRNA was significantly upregulated as measured by a qPCR, and microarray data showed that the senescence and autophagy pathways were significantly changed in astrocytes exposed to anti-SBSN antibody compared to normal immunoglobulin G exposure.
Conclusion: Our findings indicate that SBSN could be a novel autoantibody for the evaluation of suspected NPSLE, and its use may help elucidate the pathogenesis underlying this disease.
To cite this abstract in AMA style:
Ichinose K, Ohyama K, Furukawa K, Higuchi O, Nakane S, Umeda M, Koga T, Igawa T, Kawakami A. Anti-Suprabasin Antibody; A Novel Autoantibody May Contribute to the Pathogenesis of Neuropsychiatric Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/anti-suprabasin-antibody-a-novel-autoantibody-may-contribute-to-the-pathogenesis-of-neuropsychiatric-systemic-lupus-erythematosus/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-suprabasin-antibody-a-novel-autoantibody-may-contribute-to-the-pathogenesis-of-neuropsychiatric-systemic-lupus-erythematosus/