Microarray testing in patients with systemic lupus erythematosus identifies a high prevalence of CpG DNA-binding antibodies
Brunekreef, Tammo; Limper, Maarten; Melchers, Rowena; Mathsson-Alm, Linda; Dias, Jorge; Hoefer, Imo; Haitjema, Saskia; van Laar, Jacob M; Otten, Henny
(2021) Lupus science & medicine, volume 8, issue 1
(Article)
Abstract
OBJECTIVE: Many autoantibodies are known to be associated with SLE, although their role in clinical practice is limited because of low sensitivity and weak associations with clinical manifestations. There has been great interest in the discovery of new autoantibodies to use in clinical practice. In this study, we investigated 57
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new and known antibodies and their potential for diagnostics or risk stratification. METHODS: Between 2014 and 2017, residual sera of all anti-dsDNA tests in the UMC Utrecht were stored in a biobank. This included sera of patients with SLE, patients with a diagnosis of another immune-mediated inflammatory disease (IMID), patients with low (non-IMID) or medium levels of clinical suspicion of SLE but no IMID diagnosis (Rest), and self-reported healthy blood bank donors. Diagnosis and (presence of) symptoms at each blood draw were retrospectively assessed in the patient records with the Utrecht Patient-Oriented Database using a newly developed text mining algorithm. Sera of patients were analysed for the presence of 57 autoantibodies with a custom-made immunofluorescent microarray. Signal intensity cut-offs for all antigens on the microarray were set to the 95th percentile of the non-IMID control group. Differences in prevalence of autoantibodies between patients with SLE and control groups were assessed. RESULTS: Autoantibody profiles of 483 patients with SLE were compared with autoantibody profiles of 1397 patients from 4 different control groups. Anti-dsDNA was the most distinguishing feature between patients with SLE and other patients, followed by antibodies against Cytosine-phosphate-Guanine (anti-CpG) DNA motifs (p<0.0001). Antibodies against CMV (cytomegalovirus) and ASCA (anti-Saccharomyces cerevisiae antibodies) were more prevalent in patients with SLE with (a history of) lupus nephritis than patients with SLE without nephritis. CONCLUSION: Antibodies against CpG DNA motifs are prevalent in patients with SLE. Anti-CMV antibodies are associated with lupus nephritis.
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Keywords: autoantibodies, autoimmune diseases, lupus erythematosus, systemic, Immunology
ISSN: 2053-8790
Publisher: BMJ Publishing Group
Note: Funding Information: Contributors HO, JMvL, ML, LM-A and JD contributed to the conceptualisation and design of the study. IH and SH extracted relevant information from the Electronic Health Records. RM prepared and performed the serological analysis of the microarrays. TB performed data analysis and data visualisation. All authors contributed to data interpretation. TB wrote the manuscript. All authors critically reviewed the manuscript. HO acts as guarantor for this study. Funding This work was supported by Thermo Fisher Scientific (Uppsala, Sweden). Competing interests LM-A and JD are employed by Thermo Fisher Scientific. JL reports grants from Astra Zeneca, MSD, Thermo Fisher Scientific. Patient consent for publication Not applicable. Ethics approval The requirement for informed consent was waived by the biobank committee of the UMC Utrecht. This study was conducted in accordance with the Helsinki Declaration of 1975 as revised in 2014 and approved by the biobank committee of the UMC Utrecht (Toetsingscommissie Biobanken UMC Utrecht, TCBio protocol no. 16-824). Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement Data are available on reasonable request. Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise. Open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. Publisher Copyright: © Author(s) (or their employer(s)) 2021.
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