Autoantibody Profiling and Anti-Kinesin Reactivity in ANCA-Associated Vasculitis

Author:

Mescia Federica123ORCID,Bayati Shaghayegh4,Brouwer Elisabeth5,Heeringa Peter6ORCID,Toonen Erik J. M.7ORCID,Beenes Marijke7,Ball Miriam J.8,Rees Andrew J.8,Kain Renate8ORCID,Lyons Paul A.12ORCID,Nilsson Peter4ORCID,Pin Elisa4ORCID

Affiliation:

1. Department of Medicine, University of Cambridge, Cambridge CB2 0SP, UK

2. Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge CB2 0AW, UK

3. Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25121 Brescia, Italy

4. Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab, 171 65 Stockholm, Sweden

5. Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands

6. Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands

7. R&D Department, Hycult Biotech, 5405 PB Uden, The Netherlands

8. Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria

Abstract

ANCA-associated vasculitides (AAV) are rare autoimmune diseases causing inflammation and damage to small blood vessels. New autoantibody biomarkers are needed to improve the diagnosis and treatment of AAV patients. In this study, we aimed to profile the autoantibody repertoire of AAV patients using in-house developed antigen arrays to identify previously unreported antibodies linked to the disease per se, clinical subgroups, or clinical activity. A total of 1743 protein fragments representing 1561 unique proteins were screened in 229 serum samples collected from 137 AAV patients at presentation, remission, and relapse. Additionally, serum samples from healthy individuals and patients with other type of vasculitis and autoimmune-inflammatory conditions were included to evaluate the specificity of the autoantibodies identified in AAV. Autoreactivity against members of the kinesin protein family were identified in AAV patients, healthy volunteers, and disease controls. Anti-KIF4A antibodies were significantly more prevalent in AAV. We also observed possible associations between anti-kinesin antibodies and clinically relevant features within AAV patients. Further verification studies will be needed to confirm these findings.

Funder

European Union’s Horizon 2020 “RELapses prevention in chronic autoimmune disease: common mechanisms and co-morbidities (RELENT)” consortium

HEalth data Linkage for ClinicAL benefit

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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