Chronic diseases, ranging from autoimmune conditions and cancer to neurological disorders, pose significant challenges to the healthcare system. Their inherent complexity complicates early diagnosis and makes predicting treatment responses difficult.
Moreover, when dealing with unpredictable treatment responses, there is a higher risk of adverse reactions, which underscores the urgency of developing more effective personalized healthcare solutions.
Antibody biomarkers could be a potential solution when it comes to improving patient care by facilitating early detection, pinpointing disease classification, predicting treatment responses, and optimizing the selection of clinical trial participants.[1]
In contrast with RNA and protein biomarkers, which can vary due to physiological and pathological processes, antibodies directly reflect disease. Immunoprofiling, or the detailed analysis of an individual’s antibody repertoire, allows researchers to secure valuable insights into the patient’s disease state, enabling customized treatment strategies.
The distinctive advantage of antibodies as biomarkers
The humoral immune system, our body’s comprehensive immune monitoring network, continuously produces antibodies that reflect the full spectrum of disease-associated changes affecting various organs and tissues.
Changes at the protein level that stimulate antibody production could include sequence mutations, aberrant folding, or abnormal expression in terms of location and level. For instance, antibody production is a response to protein alterations in cancer and neurodegenerative diseases.[2-8]
Antibodies are excellent biomarkers as they offer a number of key benefits when it comes to using them in disease detection applications. First, they appear in early stages of disease and persist throughout its course, which can enable early disease detection and monitoring.
Second, they can be accessed via blood sampling, which provides a good insight into the body’s immune response, unlike protein profiling in blood, which only captures proteins released into the bloodstream. Moreover, antibodies can shed light on the pathways of disease-associated proteins, providing critical insights for untangling disease complexities and promoting new therapeutic discoveries.
The dual dynamics of antibody structure in immune defense
Antibody structure can be divided into two regions: the Fab variable region, which pinpoints antigens, and the Fc constant region, which carries out effector functions through receptors discovered on innate immune cells (Figure 1).[9,10]
The Fc region also defines antibody isotype (IgM, IgD, IgA, IgG, and IgE), each with unique structure and function (Table 1). As a result of the dual functionality of antibodies via their Fab and Fc regions, direct appropriate immune strategies for pathogen elimination are made possible. These isotypes are crucial for coordinating adaptive and innate immune responses and occupying a significant position in the immune defense against a range of different pathogens.
Familiarity with the various isotypes is invaluable in understanding disease, as isotypes are expressed uniquely across different diseases and stages. They can also inform drug development by indicating a patient’s inflammatory status and potential adverse reactions to treatments. For example, certain isotypes may stimulate an inflammatory response; therefore, knowledge of these can direct the administration of immune-based therapies.
Figure 1. Structure of an IgG Antibody. The Fab region binds to antigens, allowing each antibody to bind to two identical antigens simultaneously. S = disulfide bonds. Image Credit: Shutterstock
Table 1. Roles of antibody isotypes. Source: Sengenics Corporation LLC
Enhancing antibody detection through advanced technology
Conventional immunoprofiling approaches screen antibodies against peptides, denatured proteins, or proteins with unknown structures. Yet, 90 % of humoral antibodies target three-dimensional epitopes, which in turn demands cutting-edge techniques with correctly folded proteins for accurate antibody binding.[7,10]
Sengenics leverages its patented KREX® technology to ensure that only properly folded, full-length proteins are displayed on high-density protein arrays for antibody screening. Moreover, two antibody isotypes can be profiled simultaneously, providing deeper insights and awareness of the immune response to disease.
This approach supports a range of screening options, from custom panels to the i-Ome® Discovery array, encompassing over 1800 human proteins, enabling flexible, detailed disease profiling, and biomarker discovery.
Real-world applications of antibody biomarkers
A number of case studies reveal the transformative influence of using antibodies as biomarkers in disease management. For example, in autoimmune diseases like lupus, immunoprofiling revealed unique autoantibody signatures up to nine years before clinical diagnosis.[11] In amyotrophic lateral sclerosis (ALS), antibodies were generated in response to the formation of TDP-43 protein aggregates characteristic of ALS.[2]
In cancer, tumor-associated proteins elicited the production of antibodies and demonstrated great potential in predicting disease outcomes.[3-8] In non-small cell lung cancer, Patel et al. utilized Sengenics protein arrays to determine a 13 autoantibody signature highly predictive of low 5-year survival rates.[8] This signature was verified in an independent cohort with an area under the curve (AUC) of 0.842, a sensitivity of 84.2 %, and a specificity of 74.1 %.
Concluding remarks
Immunoprofiling allows for more individualized and effective management of chronic diseases by providing direct key insights into the immune system’s response to disease.
It also helps enable the identification of disease-specific and associated protein changes, acting as an important source of antibody and protein biomarkers. These biomarkers can be used for disease diagnosis, patient stratification, continuous monitoring, and the development of advanced drugs and treatments.
Developments in this area will, over time, improve patient outcomes and enhance the quality of life for those with chronic conditions.
References
- Bizzaro N. Autoantibodies as predictors of disease: the clinical and experimental evidence. Autoimmun Rev. 2007 Jun;6(6):325-33. doi: 10.1016/j.autrev.2007.01.006. Epub 2007 Jan 30. PMID: 17537376.
- Conti E, Sala G, Diamanti S, Casati M, Lunetta C, Gerardi F, Tarlarini C, Mosca L, Riva N, Falzone Y, Filippi M, Appollonio I, Ferrarese C, Tremolizzo L. Serum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis. Sci Rep. 2021 Jan 21;11(1):1978. doi: 10.1038/s41598-021-81599-5. PMID: 33479441; PMCID: PMC7820419.
- Aziz F, Smith M, M Blackburn J. Autoantibody-Based Diagnostic Biomarkers: Technological Approaches to Discovery and Validation [Internet]. Autoantibodies and Cytokines. IntechOpen; 2019. Available from: http://dx.doi.org/10.5772/intechopen.75200
- Sexauer D, Gray E, Zaenker P. Tumour- associated autoantibodies as prognostic cancer biomarkers- a review. Autoimmun Rev. 2022 Apr;21(4):103041. doi: 10.1016/j.autrev.2022.103041. Epub 2022 Jan 12. PMID: 35032685.
- Kathrikolly T, Nair SN, Mathew A, Saxena PPU, Nair S. Can serum autoantibodies be a potential early detection biomarker for breast cancer in women? A diagnostic test accuracy review and meta-analysis. Syst Rev. 2022 Oct 9;11(1):215. doi: 10.1186/s13643-022- 02088-y. PMID: 36210467; PMCID: PMC9549667.
- Zaenker P, Ziman MR. Serologic autoantibodies as diagnostic cancer biomarkers--a review. Cancer Epidemiol Biomarkers Prev. 2013 Dec;22(12):2161-81. doi: 10.1158/1055-9965.EPI-13-0621. Epub 2013 Sep 20. PMID: 24057574.
- Barlow DJ, Edwards MS, Thornton JM. Continuous and discontinuous protein antigenic determinants. Nature. 1986 Aug 21-27;322(6081):747-8. doi: 10.1038/322747a0. PMID: 2427953.
- Patel AJ, Tan TM, Richter AG, Naidu B, Blackburn JM, Middleton GW. A highly predictive autoantibody-based biomarker panel for prognosis in early-stage NSCLC with potential therapeutic implications. Br J Cancer. 2022 Feb;126(2):238-246. doi: 10.1038/s41416-021-01572-x. Epub 2021 Nov 2. PMID: 34728792; PMCID: PMC8770460.
- James, L.K., B cells defined by immunoglobulin isotypes. Clin Exp Immunol, 2022. 210(3): p. 230-239.
- Van Regenmortel, M.H.V., Mapping Epitope Structure and Activity: From One-Dimensional Prediction to Four-Dimensional Description of Antigenic Specificity. Methods, 1996. 9(3): p. 465-72
- Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, Harley JB. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003 Oct 16;349(16):1526-33. doi: 10.1056/NEJMoa021933. PMID: 14561795.
About Sengenics Corporation LLC
Sengenics, a functional proteomics company, is committed to advancing precision medicine worldwide by empowering researchers with biologically relevant and actionable insights across a broad spectrum of diseases. At the heart of its mission, Sengenics offers advanced, high-throughput tools using proprietary technology to precisely measure autoantibody biomarkers and protein interactions for basic, translational, and clinical research. Its robust tools have been leveraged by the top pharmaceutical companies and leading academic institutions to enhance disease understanding and streamline the biomarker pipeline.
Sengenics is headquartered in the U.S. and has a network of offices, distributors, and service providers across the globe.
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