Abstract
BackgroundBehcet’s disease (BD) is a chronic, multisystem-involved vasculitis and its pathogenesis remains elusive. No specific serological markers for BD diagnosis have been established. Identification of novel diagnostic biomarkers will be helpful in timely diagnostic and treatment for Behcet’s disease.ObjectiveTo screen novel autoantigens or autoantibodies with potential diagnostic value in circulating immune complexes (CICs) from BD patients.MethodsA proteomic strategy for immune complexome analysis was developed, in which CICs were separated from serum sample of 10 BD patients and 10 healthy controls and then subjected to Orbitrap mass spectrometry for autoantigen profiling. Anti-tubulin-α-1c antibody levels were further determined by enzyme-linked immunosorbent assay (ELISA) in sera of patients with BD, systemic lupus erythematosus (SLE), recurrent aphthous ulcers (RAU), ANCA associated systemic vasculitis (AASV), Takayasu's arteritis (TA) and 59 healthy controls.ResultA total of 17 potential antigens were identified in CICs from BD patients, but not in HC. The autoantibody to one of the identified antigens, tubulin-α-1c, was significantly increased in BD patients compared with that in healthy and disease controls. The sensitivity and specificity of tubulin-α-1c antibody in the diagnosis of BD in this study were 61.36% and 88.4%, respectively. Further analysis demonstrated that anti-tubulin-α-1c was associated with complications of deep venous thrombosis and erythema nodosum in BD. The levels of anti-tubulin-α-1c were also significantly correlated with the BD inflammation and disease activity markers ESR, CRP and BVAS.ConclusionAnti-tubulin-α-1c antibody is a promising biomarker in diagnosis and severity evaluation of BD and in indicating the risk of deep venous thrombosis and erythema nodosum. The immune complexome analysis by proteomic CIC autoantigen screening is a feasible way of identifying novel biomarkers in BD.
Highlights
Behcet’s Disease (BD) is an autoimmune vasculitis with multi-organ involvement, characterized by recurrent occurrence of oral and genital ulcer, skin lesions, and ophthalmological, neurological, or gastrointestinal manifestations
The immune complexome analysis by proteomic circulating immune complexes (CICs) autoantigen screening is a feasible way of identifying novel biomarkers in Behcet’s disease (BD)
An antigen profile composed of 423 proteins was identified from CICs of both BD patients and healthy controls. 17 proteins were identified in CICs from BD patients, but not in CICs from Healthy control (HC) (Table 1)
Summary
Behcet’s Disease (BD) is an autoimmune vasculitis with multi-organ involvement, characterized by recurrent occurrence of oral and genital ulcer, skin lesions, and ophthalmological, neurological, or gastrointestinal manifestations. The disease is prevalent in regions along the “Silk Road”, extending from East Asia to the Middle Eastern and the Mediterranean countries. The highest prevalence of the disease is only 14–20/100 000 along the Silk Road, and is much more rarely seen in Western countries [1,2,3]. The lack of reliable serological markers for accurate diagnosis of BD restrains the improvement of BD treatment in clinical practice [5,6,7]. Behcet’s disease (BD) is a chronic, multisystem-involved vasculitis and its pathogenesis remains elusive. Identification of novel diagnostic biomarkers will be helpful in timely diagnostic and treatment for Behcet’s disease
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