Diagnostic Uncovering Rare Immune Deficiencies Across the Life Course: The BRC INGENIOS Clinic for Severe Infection

Severe, recurrent, or unexplained infections and inflammatory conditions represent a critical unmet need in clinical medicine. In a significant subset of patients, these presentations are driven by rare underlying genetic variants affecting immune function. Without genomic investigation, patients face prolonged diagnostic odysseys, repeated admissions without a unifying diagnosis, delayed treatment, and avoidable morbidity.

The BRC Genetics of Infection Clinic was established to address this gap directly, applying whole genome sequencing, and functional immunological characterisation to patients presenting with serious infections or immune dysregulation. To date, the clinic has recruited 166 patients in total, 129 children and 37 young adults, seen between 2015 and 2025. We have made several diagnoses and genetic discoveries which advance our understanding of genetics determinants of rare immune conditions.

Confirmed diagnoses enable targeted therapies, genetic counselling, family screening, and prevention of potentially fatal recurrences. Inclusion of young adults directly addresses health inequality in access to genomic medicine, consistent with NIHR priorities around health inequalities. Integration with the NHS R15 pathway (Primary immunodeficiency disorders) ensures findings inform NHS clinical records and future commissioning, establishing replicable national infrastructure for genomic investigation of rare immune conditions across all ages.
This clinical programme has directly underpinned the team’s establishment of the newly re-funded Network of Genomics Excellence — Severe Presentations of Infection and Inflammatory Disease, supported by £1.75 million from NHS England’s Genomics Unit. Within a 3–5 year horizon, the aim is to translate novel variant discoveries into new diagnostic classifications and establish a national referral model based on the Genetics of Infection Clinic framework, informing NHS genomic pathway development for patients with severe or unexplained infection and immune dysregulation.