Autoantibodies are primarily produced by a small subset of the B cells known as B-1 cells or CD5+ B cells after the immune reactions are directed against one or more of the body's own antigens (self-antigen) (Aggarwal, 2014; Shoenfeld et al., 2013; Elkon and Casali, 2008; Wardemann and Nussenzweig, 2007). They may comprise proteins, nucleic acids, carbohydrates, lipids or various combinations of these biological materials. For example, in systemic lupus and related systemic autoimmune disorders, the dominant antigens are ribonucleoproteins or deoxyribonucleoproteins (Casali and Schettino, 1996; Elkon and Casali, 2008). Autoantibodies may be pathogenic, disease-specific and diagnostic, or of no apparent significance. They bind to non-foreign structures within the body and can be found in most well-defined autoimmune disorders. Low-level of autoantibodies occur naturally in healthy individuals and is more common among older adults (Elkon and Casali, 2008; Llorente et al., 1997). These natural autoantibodies occur in low concentrations and have weak binding affinities. Until recently, it had been thought that high-affinity autoantibodies were only associated with autoimmune conditions. However, there is increasing evidence that these autoantibodies are also involved in chronic malignancies. Several mechanisms have been proposed for the production of autoantibodies in cancer including host-immune reactions to tumor-associated antigens (TAAs), antigenic stimulation because of the destruction of malignant cells, or immune dysregulation induced by the neoplastic process (Caron et al., 2007).
Over the last few decades, the evidence of circulating autoantibodies in the sera of cancer patients has created enormous opportunities by utilizing the immune system as a source of clinically useful cancer biomarker (Finke et al., 2017; Hanash, 2003). Autoantibodies have become of particular interest as a cancer biomarker because they can be easily extracted from the serum via minimally invasive blood collection (Anderson et al., 2014; Dudas et al., 2010; Zayakin et al., 2013). Various studies have shown that antibodies to the TAAs are present in the samples of patients with different types of malignancies. Additionally, they show an increased level in very early stages of cancer and are observed in the patients with several carcinomas including breast (Anderson et al., 2010a; Bassaro et al., 2017), lung (F.M. Brichory et al., 2001; Chapman et al., 2011), gastrointestinal (Zayakin et al., 2013), ovarian (Anderson et al., 2014), colorectal (Álvarez-Fernández et al., 2016), oesophagal (Chen et al., 2017), hepatocellular (Ying et al., 2017) and prostate (Bradford et al., 2006) cancers. Most extensively studied tumor-associated autoantibodies are the autoantibodies against p53 (Yadav et al., 2017), L-myc (Yamamoto et al., 1996), glycosylated annexin I, annexin II (F.M. Brichory et al., 2001) or HER2-neu (Caron et al., 2007). Detection of autoantibodies also reported during the cellular alteration to malignancy. Therefore, these circulating biomarkers present themselves as an early reporter of the aberrant cellular mechanism involved in tumorigenesis. For instance, anti-tumor protein p53 antibodies reported to detectable as early as 17–47 months earlier to clinical tumor manifestation in uranium workers with the high risk of lung cancer development (Tan and Zhang, 2008; Zaenker et al., 2016). Furthermore, autoantibodies may be valuable biomarkers as they are stable serological proteins with high levels in serum even during low levels of the corresponding antigens (Anderson and LaBaer, 2005; Lu et al., 2008). Even if different cancer biomarker has discovered, they are yet limited in clinics due to their poor predictive values.
To date, various conventional methods such as enzyme-linked immunosorbent assay (ELISA) or sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS/PAGE) have employed to detect the autoantibodies in serum (Tan et al., 2009). ELISA is one of the most widely used detection techniques, relying on a sandwich immunoassay (Anderson et al., 2010b; Bassaro et al., 2017; Chapman et al., 2008; Takeda et al., 2001). Improvements in the technologies such as proteomic-based platform have enabled the panel of TAAs that shows better diagnostic value than a single TAA markerB体育官方入口. In recent years, much attention has been given to developing new strategies based on electrochemistry (Garranzo-Asensio et al., 2016; Masud et al., 2017; Yadav et al., 2017), microfluidics (Hu et al., 2009)(López-Muñoz et al., 2017) and surface plasmon resonance sensor (Ladd et al., 2009; Soler et al., 2016). Among these techniques, electrochemical biosensors have shown great promise because they are fast responsive, user-friendly and cost-effective. Furthermore, microfluidic-based platforms are well suited for overall analytical performance (Hu et al., 2009).Bsports官网
As the field has progressed rapidly in recent years, several review articles had been published (Bassaro et al., 2017; Fortner et al., 2017; Macdonald et al., 2017; Tan et al., 2009; Wu et al., 2017; Zaenker et al., 2016). Most of these articles are based on the biogenesis, discovery and diagnostic development of tumor-associated autoantibodies. However, there is a lack of systemic study, which discusses the potential challenges associated with the detection method or diagnostic development for tumor-associated autoantibodies. In this review, we not only discuss the role of tumor-associated autoantibodies in cancer diagnosis but also identify the challenges encountered while detecting the autoantibodies. We also propose solutions to translate the autoantibodies from research evidence into clinical practice for diagnosis and prognosis of cancer.
