Description
Birdshot chorioretinopathy (BCR) is a chronic, autoimmune form of posterior uveitis that targets the retina and can result in progressive visual deterioration or permanent blindness. It has a striking genetic association with the HLA A29 molecule, which plays a central role in disease susceptibility. As a result, BCR is widely regarded as a prototypical HLA linked autoimmune ocular disease.
Management of BCR relies on early, aggressive, and sustained immunosuppression. Although, many patients exhibit only a partial response to therapy, and a significant proportion develop treatment resistance over time. Even the most effective immunosuppressant —adalimumab—only has a 60% response rate, highlighting the substantial unmet need in understanding and predicting therapeutic outcomes.
To address this, we applied the TruCulture whole blood stimulation system to a cohort of adalimumab naïve BCR patients in order to investigate their systemic immune response and identify biomarker signatures associated with long term treatment success. Whole blood was collected and incubated for 22 hours in the presence or absence of systemic or targeted immune stimuli, enabling controlled profiling of patient specific inflammatory pathways.
Using the OLINK Reveal proteomic platform, we quantified the expression of over 1,000 proteins across three conditions — Null, LPS, and LPS + Adalimumab. This dataset provides a high resolution view of cytokine responses, inflammatory signalling, and drug modulated pathways. By integrating these findings with each patient’s clinical history and genetic background, we aim to define immune profiles that can guide clinicians toward more targeted and effective treatment strategies for BCR.
Lay Abstract
Birdshot chorioretinopathy (BCR) is a rare, chronic eye disease where the immune system mistakenly attacks the retina, potentially causing permanent blindness. Strongly linked to the HLA-A29 genetic marker, it is a classic autoimmune disorder. Current treatments rely on strong immune-suppressing drugs, but these do not work for everyone. Even the most effective drug, adalimumab, helps only about 60% of patients, while others see little improvement or develop resistance. This highlights a critical need to better predict which treatments will work for specific individuals.
To address this, I am using the TruCulture system to analyze blood samples from patients who have never taken adalimumab. My goal is to identify specific biomarkers linked to long-term treatment success. I incubate these samples with various immune stimuli to profile patient-specific inflammatory pathways. Using the OLINK Reveal platform, I quantify over 1,000 proteins to map how each patient’s immune system reacts. By combining this data with clinical history and genetics, I aim to define unique immune profiles. Ultimately, this research hopes to help doctors choose the right treatment sooner, preventing vision loss and avoiding ineffective therapies for BCR patients.
| Lay Title | Investigating potential markers for treatment success in Birdshot Chorioretinopathy |
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| Role | PhD Student |