IMMUNOLOGY2026™ Conference Recordings For Attendees-Uncovering the immunological determinants of progressive liver disease in X-linked Myotubular Myopathy

Uncovering the immunological determinants of progressive liver disease in X-linked Myotubular Myopathy

Video Transcription

Video Summary

This talk described research into why XLMTM gene therapy patients developed severe liver disease, despite preclinical mouse models showing no liver toxicity. The speaker proposed that missing environmental factors—especially diet and infection—may “unmask” liver vulnerability in MTM1-deficient mice. When knockout mice were fed a refined diet similar to patients’ tube feeds, they developed cholestasis, abnormal liver tests, immune-cell infiltration, and inflammatory gene signatures, unlike mice on standard chow. Gene therapy further increased cytokine responses in these diet-stressed mice. Viral challenge with H1N1 and LPS-induced endotoxemia also caused exaggerated inflammation and much higher mortality in knockout animals, with elevated cytokines such as IL-6 and TNF-related signals. Overall, the data support a multi-hit model in which MTM1 loss plus environmental stressors drive liver injury through abnormal immune activation.

Meta Tag

Date April 19, 2026 10:00 AM - 10:15 AM

Room 153 AB

Session Primary Immune Deficiency and Immune Dysregulation

Speaker Yingxuan Zhu

Track Immune Mechanisms of Human Disease (HUM)

Year 2026

Keywords

XLMTM

MTM1 deficiency

liver disease

diet stress

immune activation

April 19, 2026 10:00 AM - 10:15 AM

153 AB

Primary Immune Deficiency and Immune Dysregulation

Yingxuan Zhu

Immune Mechanisms of Human Disease (HUM)

2026