Complement diagnostics for eye and kidney diseases
The complement system(opens in new window) is part of our immune defence that contributes to the elimination of pathogens and damaged cells. Disruption of its balance can lead to the immune system attacking the body’s own tissues, contributing to inflammatory and degenerative diseases such as age-related macular degeneration, kidney disorders and certain autoimmune conditions. The factor H(opens in new window) (FH) protein family keeps complement activity in check. However, despite decades of genetic research, the functional roles of individual FH-related (FHR) proteins have remained largely unknown.
New tools to study immune regulation
The EU-funded SciFiMed(opens in new window) project set out to fill this knowledge gap. Although it was known that the FH family was associated with diseases of the eye and kidney, the tools to further explore the different disease-specific pathogenic mechanisms were missing. “Our goal was to develop diagnostic technology that will shed light into the role of the complement in various pathologies,” explains project coordinator Diana Pauly. The project developed and validated antibodies and ELISA kits for the FH protein family, which are now available to researchers worldwide. These tools allow scientists to quantify not just FH but also the various FHR proteins, enabling more precise measurement across clinical studies. The team also created functional assays that go beyond standard protein quantification, determining the regulatory capacity of FH and its potential to protect against inflammation. This shift from determining concentration to estimating activity provides a clearer picture of how mutations, autoantibodies or external factors alter immune responses. The assay can also be used to screen potential therapeutics that modulate FH activity, thereby accelerating drug discovery for complement-mediated diseases.
Understanding disease mechanisms
Using these tools, SciFiMed researchers performed clinical screening studies across several disease contexts. Their findings suggest that certain FHR proteins may contribute to inflammation in conditions not previously linked to the complement system. Although confirmation in larger cohorts is necessary to determine the full clinical significance, these results open new avenues for understanding disease mechanisms By shifting complement research from genetic associations to functional validation, SciFiMed has laid the groundwork for more precise risk assessment and patient stratification. The project’s insights could eventually inform diagnostic tests to identify individuals at higher risk of complement-driven diseases.
Validation and clinical potential
The functional FH assay has already reached technology readiness level 3-4, meaning its feasibility and performance have been demonstrated in laboratory settings. Larger studies on clinical samples are now underway, and intellectual property protection is in progress. “Before we can consider point-of-care use, we must validate the functional FH assay in clinical trials,” emphasises Pauly. SciFiMed has taken a huge step forward by equipping the scientific community with powerful tools and methodologies. The ELISA kits and functional assay are expected to assist researchers in understanding how the FH family contributes to different eye and kidney pathologies. Long-term, these innovations will contribute to precision diagnostics and targeted therapies for conditions that once seemed beyond reach.
