Host Genomics Could Reshape How Doctors Diagnose Immune Disorders and Treat Infections

Genomic technologies are now widely used in clinical care to identify pathogens and determine their antimicrobial susceptibilities, yet far less use is made of the patient’s own germline genomic variations in managing infectious disease. A group of more than 30 clinical immunologists, infectious disease specialists and geneticists met to outline the challenges and opportunities surrounding this gap, arguing that host genomics deserves a larger role in everyday infection care.

Their discussion, published as a mini review in Frontiers in Genetics, centers on inborn errors of immunity, or IEIs. These are genetic conditions that impair immune function, and most of them are rare. The authors emphasize that such conditions can be detected before severe complications develop, which is a key argument for expanding genetic testing rather than reserving it for patients who have already suffered serious infections.

Beyond rare diagnoses, the participants outlined several ways host genomics could assist with more common infections. These include risk stratification for severe disease, selection of antimicrobial therapy, and pharmacogenomic-guided dosing, in which a patient’s genetic makeup informs how drugs are prescribed and dosed.

The experts also identified substantial obstacles that currently limit the clinical use of host genomics. Among these are payer requirements that patients undergo extensive conventional diagnostics before genetic testing will be approved, a lack of interoperability between electronic health record systems, and limited evidence of efficacy and cost-effectiveness, a problem compounded by the individual rarity of most inborn errors of immunity.

That rarity creates a structural dilemma for evidence generation. Because each IEI affects few patients, assembling the data needed to demonstrate clinical benefit and economic value is difficult, and payers may therefore be reluctant to cover testing, reinforcing the cycle of limited evidence and limited adoption.

To broaden the use of host genomics, the group set out several priorities. These include publicizing the indicators of inborn errors of immunity so that clinicians recognize when testing is warranted, building those indicators into electronic health record informatics systems, and promoting multidisciplinary approaches to identifying patients with IEIs.

The multidisciplinary element reflects the composition of the meeting itself, which brought together specialists from immunology, infectious disease and genetics. The authors suggest that collaboration across these fields is needed to spot patients whose infection patterns may signal an underlying genetic susceptibility that a single specialty might miss.

The review is a perspective on the field rather than a report of new clinical trial results, and its recommendations represent the consensus views of the participating experts. It frames host genomics as an underused complement to pathogen-focused genomics, with potential applications spanning diagnosis of rare immune disorders, prediction of severe infection risk, and optimization of antimicrobial treatment.

As genomic sequencing becomes more routine, the authors argue that integrating germline findings into infectious disease management could shift care toward earlier detection of immune vulnerabilities and more precisely tailored therapy, provided the identified barriers to coverage, data sharing and clinical evidence can be addressed.

Subject of Research: The use of host germline genomics in diagnosing inborn errors of immunity and tailoring infectious disease treatment

Article Title: Host genomics in diagnosing inborn errors of immunity and tailoring infectious disease treatments

Article References: Buyon, L., Berg, J. S., Bogunovic, D., Green, E. D., Holland, S. M., Narula, J., Read, S. W., Rupert, A., Marrazzo, J. M., & Puck, J. M. (2026). Host genomics in diagnosing inborn errors of immunity and tailoring infectious disease treatments. Frontiers in Genetics, 17, Article 1984349. https://doi.org/10.3389/fgene.2026.1984349

Image Credits: AI Generated

DOI: 10.3389/fgene.2026.1984349

Keywords: host genomics, inborn errors of immunity, infectious diseases, primary immunodeficiency, precision medicine, genetic testing, electronic health records, risk stratification, pharmacogenomics, antimicrobial therapy, clinical decision support, Host