ISG15 and USP18 gene defects that cause harmful type I interferon disease

Human ISG15 and USP18 Deficiencies Underlying Type I Interferonopathies

NIH-funded research Columbia University Health Sciences · NIH-11133030

This project explores how genetic problems with ISG15 or USP18 lead to harmful type I interferon inflammation in children and others with rare interferon-related autoimmune and neurologic conditions.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionColumbia University Health Sciences NIH-funded
Lab location1 site (New York, United States)
Project IDNIH-11133030 on NIH RePORTER

What this research studies

This work focuses on people (often children) with ISG15 or USP18 genetic deficiencies that cause type I interferonopathy. Researchers will study blood cells and tissue samples from affected patients and perform lab experiments on patient-derived cells, together with animal studies, to find where interferon responses become harmful. They will use molecular and immunology techniques to map tissue-specific effects and test ways to dial down damaging interferon signals. The goal is to use those findings to guide the development of targeted treatments.

Who could benefit from this research

Good fit: Ideal candidates are children or adults diagnosed with type I interferonopathies or known ISG15 or USP18 genetic defects, or those with clinical signs similar to Aicardi–Goutières syndrome.

Not a fit: People whose illnesses are not driven by type I interferon signaling or who lack ISG15/USP18 mutations are unlikely to benefit directly.

Why it matters

Potential benefit: If successful, this research could point to targeted treatments that reduce harmful interferon-driven inflammation and improve neurologic and autoimmune symptoms.

How similar studies have performed: Genetic links between ISG15/USP18 deficiencies and interferonopathies have been previously reported, but translating those findings into effective therapies is still early and largely unproven.

Where this research is happening

New York, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions Acquired Immune Deficiency Syndrome VirusAcquired Immunodeficiency Syndrome VirusAicardi Goutieres syndrome
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.