How much autoimmunity is caused by EBV infection?

About the Project

Title: How much autoimmunity is caused by EBV infection?

Synopsis: This project will determine whether distinct patterns of antibody responses to the EBV proteome are present across autoimmune diseases. Using high-resolution serological profiling, the study will identify which autoimmune conditions show evidence of EBV-driven pathology and explore how host genetics modifies these antiviral immune responses.

Details: Epstein–Barr virus (EBV) infects more than 90% of the global population and has long been associated with a wide range of malignancies and autoimmune diseases. Multiple sclerosis (MS) provides the most compelling example of EBV-associated autoimmunity. Large epidemiological studies demonstrate that EBV infection precedes disease onset and is associated with dramatically increased risk, while immunological studies show abnormal antiviral responses in affected individuals. However, beyond MS, whether EBV plays a causal or contributory role in other autoimmune diseases remains unclear.

A major challenge in addressing this question is that most studies rely on binary measures of EBV exposure, classifying individuals as seropositive or seronegative. Because EBV infection is almost universal in adults, this approach requires extremely large cohorts to detect disease associations. Recent work from the FutureMS study (under review) demonstrates that a more informative strategy is to characterise antibody responses across the EBV proteome. Individuals with MS show distinctive patterns of antibody breadth and intensity directed against latent viral antigens, reflecting differences in the host–virus equilibrium. These antibody “fingerprints” can discriminate MS cases from EBV-infected controls with high accuracy using serological data alone.

This project will test the hypothesis that similar EBV-specific immune signatures may be present across other autoimmune diseases, providing a new framework for identifying EBV-associated autoimmunity.

The first objective is to establish high-resolution antibody profiling across the EBV proteome. The student will implement multiplex serological assays, developed in the Gilbert Laboratory, to quantify antibody responses against a panel of EBV antigens spanning latent and lytic phases of infection. These assays will build on established ELISA-based and high-throughput immunoassay platforms within the Hunt laboratory, with methodological support from the Gilbert laboratory.

The second objective is to determine whether distinct EBV antibody signatures are present across autoimmune diseases. Using samples from well-characterised clinical cohorts, including individuals with Sjögren’s syndrome and systemic lupus erythematosus through collaborations in Cambridge, Newcastle (e.g. Prof Fai Ng, Primary Sjogren Syndrome Registry) and Edinburgh, the student will compare EBV antibody responses across diseases and identify disease-specific patterns of antiviral immunity.

The third objective is to integrate serological data with host genetics and population-scale datasets. UK Biobank now includes quantitative measurements of EBV antibody responses, providing an unprecedented opportunity to investigate how genetic risk variants for autoimmune diseases influence antiviral immunity. By combining serology, genetics and clinical phenotypes, the student will test whether EBV-specific immune signatures mediate genetic susceptibility across diseases.

Finally, the project will explore how EBV responses relate to disease stage in conditions characterised by progressive autoantibody accumulation, such as systemic lupus erythematosus and Sjögren’s syndrome. By analysing EBV antibody responses alongside established autoantibody profiles (e.g. ANA and anti-dsDNA antibodies), the student will examine whether antiviral immune signatures to EBV nuclear antigens (EBNA proteins) precede or accompany the development of pathogenic autoimmunity against host nuclear antigens (e.g. ANA, dsDNA, anti-Ro, anti-La, etc.).

This project integrates viral immunology, clinical cohort studies, and population genetics to move beyond binary measures of viral exposure. By identifying EBV-specific immune signatures across autoimmune diseases, the work has the potential to redefine how viral infection contributes to autoimmune pathogenesis and to identify patient groups most likely to benefit from emerging EBV-targeted therapies.

Potential impact: Identifying autoimmune diseases driven by EBV could redefine disease classification and highlight patient groups likely to benefit from antiviral or EBV-targeted therapies, including vaccines and T-cell–based treatments currently under development.

Training: The student will be primarily based within the Hunt laboratory at the Centre for Clinical Brain Sciences, an internationally recognised environment for translational neuroimmunology and clinical cohort research in multiple sclerosis. The lab hosts a multidisciplinary team including clinicians, immunologists and data scientists working across large longitudinal studies such as FutureMS and PrecisionMS. This environment will provide the student with training in clinical cohort science, biomarker discovery, and translational immunology.

The student will gain practical training in immunological and serological techniques including ELISA-based antibody assays, multiplex immunoassays and high-sensitivity protein detection platforms such as SIMOA. They will also develop skills in experimental design, statistical analysis and handling large-scale clinical datasets. Opportunities will be available to engage directly with ongoing clinical studies, providing insight into how mechanistic laboratory findings can be integrated with patient cohorts and disease phenotyping.

Through close collaboration with the Gilbert laboratory at the MRC Human Genetics Unit, the student will receive additional training in molecular and cellular biology approaches relevant to viral immunology, including assay development, antibody profiling and high-throughput experimental workflows. This cross-laboratory structure will allow the student to gain experience across both clinical and molecular research environments.

The student will also benefit from the broader training programmes available through the University of Edinburgh and Edinburgh Neuroscience, including workshops in bioinformatics, statistics, research integrity and science communication. Regular lab meetings, journal clubs and presentation opportunities will support the development of critical thinking, scientific communication and collaborative research skills.

Recruitment: This project would suit a student with a strong background in biomedical sciences, immunology, molecular biology, or a related discipline. Applicants should have a good undergraduate degree (or equivalent) in medicine, biological sciences, genetics, immunology, or a quantitative biomedical field. Prior laboratory experience in immunological or molecular techniques (e.g. ELISA, flow cytometry, PCR-based methods or cell culture) would be advantageous but is not essential. Experience with data analysis or statistical programming (e.g. R or Python) would also be beneficial given the integration of serological and cohort datasets. The project is interdisciplinary and will involve collaboration across clinical and molecular research environments; therefore applicants should demonstrate strong quantitative reasoning, curiosity about host–pathogen interactions, and enthusiasm for translational research linking laboratory science with human disease.

Apply: All applications must be submitted through the Future Medicine PhD fellowships website.

Funding Notes

Students will receive a stipend at UKRI levels, plus £30K in travel and research funds across all three years of the fellowship. All University fees will be covered.

The fellowships are open to students who are eligible for home fees at Edinburgh - i.e. you must be a UK national, or have settled status, and have. been "ordinarily resident" in the UK for the three years immediately before the start of the fellowship. Other international applicants are not eligible for these fellowships.