Autoimmune diseases hinge on misdirected humoral immunity. If we can pinpoint which self-antigens attract patient autoantibodies—and map the epitopes they prefer—we gain direct levers for mechanism, diagnostics, and targeted immunomodulation. Phage display offers that resolution at scale: it turns the entire human proteome (or any selected tissue proteome) into a searchable, sequence-addressable library and lets patient sera "fish out" the true disease-relevant epitopes. As a core part of our Phage Display for Biomarker Discovery Services, we run end-to-end campaigns at Creative Biolabs to discover and prioritize these autoantibody targets using strong controls, stringent selection, and reliable validation.
To appreciate the elegance of phage display, one must first understand the tool at its core: the bacteriophage.
Fig.1 Bacteriophage replication cycles: the lytic vs. lysogenic cycle.
The presence of autoantibodies in autoimmune diseases is a defining feature of autoimmunity, serving as a critical link between the innate and adaptive immune systems. These antibodies, which erroneously target the body's own proteins, lipids, and nucleic acids, are not only invaluable biomarkers for diagnosis and prognosis but are also key drivers of pathology in conditions like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS)1. The process of autoantibody discovery, identifying the specific self-antigens (autoantigens) they target, is a paramount objective in immunology. Phage display was introduced in 1985 (later recognized by the 2018 Nobel Prize in Chemistry) to link genotype and phenotype on a bacteriophage surface, enabling selection of binders to almost any biological target. The power comes from libraries with billions of unique variants, each physically displaying a peptide/protein fragment while carrying its encoding DNA for rapid identification. High-quality libraries typically span ~108 to 1011 unique clones, and antibody or peptide inserts are fused to coat proteins (commonly pIII on filamentous phage) for functional display—a design that keeps the readout directly sequence-resolvable after biopanning. For autoimmune research, that means you can screen patient sera against comprehensive cDNA or peptide libraries to pull down disease-reactive self-antigens and then rank them by enrichment and confirm with our assays.
We use cDNA phage display libraries representing the human proteome—or focused, tissue-specific proteomes—to systematically screen patient sera for reactive autoantibodies. This approach pinpoints self-antigens that drive pathology, clarifies disease mechanisms, and seeds candidate targets for research-use diagnostics and targeted immunomodulation.
Our phage display platform has enabled researchers to uncover autoantibody profiles in a wide range of diseases, as illustrated in the following table. While these examples are well-characterized, our platform is focused on discovering novel, disease-driving or disease-stratifying autoantibodies, particularly in heterogeneous or poorly understood conditions.
| Autoantibody | Disease Association |
|---|---|
| Anti-dsDNA | Systemic lupus erythematosus (SLE) |
| Anti-MBP | Multiple sclerosis |
| Anti-GAD65 | Type 1 diabetes |
| Anti-CCP | Rheumatoid arthritis |
| Anti-TPO | Hashimoto's thyroiditis |
| Anti-AQP4 | Neuromyelitis optica |
| Anti-PL-7 / PL-12 | Myositis syndromes |
Our application is powered by a modular set of phage display and immunology services, seamlessly integrated to support your research.
The foundation of any successful screen is the quality and diversity of the library. We don't believe in a one-size-fits-all approach. We construct custom libraries tailored to the specific research question, including:
This is the core discovery phase. The phage display library is incubated with patient samples (serum, plasma, CSF, etc.). Phages displaying proteins or peptides that are recognized by the patient's autoantibodies are captured.
The specifically bound phages are eluted and then re-amplified by infecting a fresh culture of E. coli. This amplification step creates a highly enriched sub-library for the next round of panning or for final analysis. Then we apply the power of NGS to the enriched phage pool.
A list of candidates is only the beginning. We complete the discovery process with rigorous validation. We express the candidate proteins, purify them, and use them in the following assays to confirm their reactivity with a larger cohort of patient samples. This crucial step validates the findings from the phage display screen and confirms the relevance of the newly identified autoantigen.
Our integrated autoantigen discovery platform is built upon a foundation of modular, expert-led services. This allows us to customize each project to your exact specifications, whether you need an end-to-end solution or a specific standalone service.
Whether you are investigating a newly defined autoimmune syndrome or need to stratify known disease subtypes, Creative Biolabs offers a powerful, reproducible, and fully supported solution for autoantibody discovery. Share your indication, sample availability, and study goals. We'll propose a fit-for-purpose selection strategy, library plan, and validation package aligned to your downstream assays and budget, keeping the workflow transparent and the deliverables decision-ready. for more details!
Q: Are bacteriophages viruses?
A: Yes, bacteriophages are viruses that infect bacteria. In phage display, they serve as tools to present peptides or proteins externally while carrying the corresponding DNA internally. Since they do not infect human cells, bacteriophages are safe for laboratory use and ideal for linking binding properties to sequence information in antibody or antigen discovery.
Q: What is phage display for antibody selection?
A: Phage display is a high-throughput method where foreign peptides or protein fragments are fused to bacteriophage coat proteins and displayed on the phage surface. In antibody selection, this system allows the screening of billions of variants to isolate those that specifically bind a target of interest, enabling precise identification of binding partners from large libraries.
Q: What is targeted by the autoantibodies in an autoimmune disease?
A: Autoantibodies recognize and bind to self-antigens, which may include nuclear proteins, cell-surface receptors, structural proteins, or tissue-specific molecules. These interactions can contribute to inflammation and tissue damage. Identifying these targets is critical for understanding disease mechanisms and developing research-use biomarkers or therapeutic strategies.
Q: What is an autoantibody test for autoimmune disease?
A: An autoantibody test detects the presence of self-reactive antibodies in serum or plasma, often used to support clinical diagnosis. Our phage display platform extends beyond standard panels by uncovering unknown or disease-specific autoantigens, enabling more comprehensive autoantibody profiling for research and biomarker development purposes.
Q: What are the limitations of phage display?
A: While phage display is powerful for identifying linear or short conformational epitopes, it may not fully represent complex tertiary structures or post-translational modifications. However, our platform mitigates these gaps by using complementary strategies such as cyclic peptide libraries and validating hits with recombinant full-length proteins in orthogonal assays.
Q: Is it possible to use CSF or tissue fluid instead of serum for screening?
A: Yes, while serum or plasma are most commonly used, we can accommodate cerebrospinal fluid (CSF), synovial fluid, or other matrices depending on the disease and sample availability. We adjust the selection protocol accordingly to maintain binding sensitivity and reduce background.
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Please kindly note that our services can only be used to support research purposes (Not for clinical use).
Creative Biolabs is a globally recognized phage company. Creative Biolabs is committed to providing researchers with the most reliable service and the most competitive price.
