Bicaudal D2 is a novel autoantibody target in systemic sclerosis that shares a key epitope with CENP-A but has a distinct clinical phenotype.

Marvin J Fritzler, Marie Hudson, May Y Choi, Michael Mahler, Mianbo Wang, Chelsea Bentow, Jay Milo, Murray Baron

Journal: Autoimmunity reviews 2018;17(3):267-275

PMID: 29369808

Full Text on Elsevier Science View on PubMed

Abstract

We studied the clinical correlations and epitopes of autoantibodies directed to a novel autoantigen, Bicaudal D (BICD2), in systemic sclerosis (SSc) and reviewed its relationship to centromere protein A (CENP-A). 451 SSc sera were tested for anti-BICD2 using a paramagnetic bead immunoassay and then univariate and multivariate logistic regression was used to study the association between anti-BICD2 and demographic and clinical parameters as well as other SSc-related autoantibodies. Epitope mapping was performed on solid phase matrices. 25.7% (116/451) SSc sera were anti-BICD2 positive, of which 19.0% had single specificity anti-BICD2 and 81.0% had other autoantibodies, notably anti-CENP (83/94; 88.3%). Compared to anti-BICD2 negative subjects (335/451), single specificity anti-BICD2 subjects were more likely to have an inflammatory myopathy (IM; 31.8% vs. 9.6%, p=.004) and interstitial lung disease (ILD; 52.4% vs. 29.0%, p=.024). Epitope mapping revealed a serine- and proline-rich nonapeptide SPSPGSSLP comprising amino acids 606-614 of BICD2, shared with CENP-A but not CENP-B. We observed that autoantibodies to BICD2 represent a new biomarker as they were detected in patients without other SSc-specific autoantibodies and were the second most common autoantibody identified in this SSc cohort. Our data indicate that the major cross-reactive epitope is associated with anti-CENP-A but, unlike anti-CENP, single specificity anti-BICD2 antibodies associate with ILD and IM.

Address: Cumming School of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, Alberta T2N4N1, Canada. Electronic address: [email protected].; Department of Medicine, McGill University, Montréal, Quebec, Canada; Division of Rheumatology, Jewish General Hospital, Montréal, Quebec, Canada; Lady Davis Institute, Jewish General Hospital, Montréal, Quebec, Canada. Electronic address: [email protected].; Cumming School of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, Alberta T2N4N1, Canada. Electronic address: [email protected].; Inova Diagnostics, Division of Research, San Diego, CA, USA. Electronic address: [email protected].; Lady Davis Institute, Jewish General Hospital, Montréal, Quebec, Canada. Electronic address: [email protected].; Inova Diagnostics, Division of Research, San Diego, CA, USA. Electronic address: [email protected].; Inova Diagnostics, Division of Research, San Diego, CA, USA. Electronic address: [email protected].; Department of Medicine, McGill University, Montréal, Quebec, Canada; Division of Rheumatology, Jewish General Hospital, Montréal, Quebec, Canada. Electronic address: [email protected].; Division of Rheumatology, Department of Medicine, Western University, London, Ontario, Canada.; Department of Medicine, McGill University, Division of Rheumatology Jewish General Hospital, Montreal, Quebec, Canada.; Deceased, Division of Rheumatology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.; Rheumatology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.; Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.; Division of Rheumatology, The Moncton Hospital, Moncton, New Brunswick, Canada.; Department of Medicine, Cumming School of Medicine, Calgary, Alberta, Canada.; Department of Medicine, Université de Sherbooke, Sherbrooke, Quebec, Canada.; Division of Rheumatology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.; Division of Rheumatology, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.; Department of Rheumatology, Hôpital Notre-Dame, Montreal, Quebec, Canada.; Medicine, Southlake Regional Health Centre, Newmarke, Ontario, Canada.; Division of Rheumatology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.; Faculty of Medicine, Université Laval, Quebec, Canada.; Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

DOI: 10.1016/j.autrev.2018.01.006

Link outs

Free resources

Medical:

https://medlineplus.gov/scleroderma.html

Other Literature Sources:

https://scite.ai/reports/29369808

Subscription / membership required

Full Text Sources:

MeSH Terms: Autoantibodies, Centromere Protein A, Cohort Studies, Female, Humans, Middle Aged, Phenotype, Scleroderma, Systemic