Detection of Multiple Autoantibodies in Patients with Ankylosing Spondylitis Using Nucleic Acid Programmable Protein Arrays

Abstract

Ankylosing spondylitis (AS) is a common, inflammatory rheumatic disease that primarily affects the axial skeleton and is associated with sacroiliitis, uveitis, and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine whether plasma from patients with AS contained autoantibodies and, if so, characterize and quantify this response in comparison to patients with rheumatoid arthritis (RA) and healthy controls. Two high density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA, and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis to determine the patterns of signaling cascades or tissue origin. 44% of patients with ankylosing spondylitis demonstrated a broad autoantibody response, as compared with 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The autoantibody responses in the AS patients were targeted toward connective, skeletal, and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic acid programmable protein arrays constitute a powerful tool to study autoimmune diseases.

Serum levels of novel noggin and sclerostin-immune complexes are elevated in ankylosing spondylitis

“…However, AS has long been viewed as a seronegative disease, notable for the lack of autoantibodies, which are the hallmarks of autoimmune rheumatic diseases such as lupus 19. There has been a recent report of autoantibodies recognising skeletal/connective tissue antigens in AS,20 but the relevance of these autoantibodies to AS pathogenesis remains unclear.…”

Utility of Autoantibodies as Biomarkers for Diagnosis and Staging of Neurodegenerative Diseases

“…These proteins are generated using in vitro transcription/translation methods. Several reports of utilizing this technology to identify novel autoantibodies for conditions like juvenile arthritis (Gibson et al, 2012), ankylosing spondylitis (Wright et al, 2012), and type 1 diabetes (Miersch et al, 2013) have been published.…”

Comorbid autoimmune pathology in patients treated with disease modifying drugs

“…Возможно, при использовании новых методов, таких как программируемые аминокислотами бел-ковые массивы, а также новых методов статистики удастся выявить ранее неизвестные антитела, как это было сделано для анкилозирующего спондило-артрита [81], а также оценить их связь с выраженно-стью отдельных клинических проявлений, как в се-рологически-эпидемиологических исследованиях, в которых изучалась склеродермия [82].…”