Developing antibody based diagnostic tests

Context:

The biophysical features of antibodies are exquisitely sensitive to the environment of the body at the time of production, and changes in these features have been observed across health and disease, with dramatic changes noted with age, during pregnancy, across geographic areas, and with autoimmune disease, infection, and malignancy. Importantly, these changes in antibody features can be harnessed to develop antibody-based diagnostic tests that can be used to guide clinical care of patients. As such, Systems Serology can be used to identify the antibody features and functions that discriminate particular patient populations, which can then be used to develop more effective diagnostic tests.

Problem:

Illustration of Tubuculosis in the body

Tuberculosis is the leading cause of infectious disease deaths worldwide. Complicating the effective treatment of tuberculosis patients is that an accurate and cost-effective diagnostic test is lacking. The currently used clinical tests largely rely on the use of nonspecific clinical symptoms, expensive microbial tests, and T cell–based tests that cannot discriminate between individuals with latent infection who are clinically well and the subset of individuals in this population who progress to active tuberculosis disease. As a simple point-of-care diagnostic with an enhanced ability to distinguish latent from active tuberculosis could dramatically limit the spread of this disease, Systems Serology was used to identify the antibody features and functions that could distinguish patients with active infection from those with latent infection.

Systems Serology Application:

Innate Antibody Fc effector profile

Reprinted from Cell, 167(2), Lenette, LL, et al.,
A Functional Role for Antibodies in Tuberculosis,
433-443, 2016, with permission from Elsevier.

Individuals with either latent or active tuberculosis generated antibody responses against the bacteria. However, these responses were functionally distinct, with latently infected individuals demonstrating increased antibody-dependent NK cell functions, whereas actively infected individuals demonstrated increased antibody-dependent phagocytic responses. In addition to these differences in functionality, significant differences in the biophysical features of the bacteria-specific bacteria were observed including increased binding to FCGR3 and unique antibody glycosylation patterns. Combined, these data suggest that individuals with active infection have an antibody profile that is functionally and biophysically distinct from individuals with latent infection.


Conclusion:

Biomarkers are important for the diagnosis and management of disease, providing a means to predict development of and diagnose a disease, predict response to particular therapies, and monitor disease progression and treatment efficacy. Antibodies are increasingly being recognized as potential biomarkers, demonstrating diagnostic and prognostic potential across a range of diseases, including autoimmune disease, infection, malignancies, and Alzheimer’s disease. Beyond the mere presence of particular antibodies, changes in the functional or biophysical features of antibodies has the potential to more precisely distinguish patient groups or predict outcome, potentially allowing for more individualized care. The Systems Serology suite of assays offered by SeromYx provides an opportunity to identify potential biomarkers that can distinguish patient populations or predict disease progression, providing the information critical for the development of cost-effective, point-of-care diagnostic tests and personalized medicine.

References

Lu LL, et al., Functional Role for Antibodies in Tuberculosis. Cell. 2016 Oct 6; 167(2): 433–443.e14.

updated: 2 weeks ago