Garvan Institute Researchers Overturn Longstanding Theory on Rare Inflammatory Disease Mevalonate Kinase Deficiency

Garvan Institute researchers find natural killer cells cause MKD inflammation, opening the door for JAK inhibitor treatments for this rare immune condition.

By: AXL Media

Published: May 1, 2026, 11:06 AM EDT

Source: Information for this report was sourced from EurekAlert!

A Fundamental Shift in Understanding Autoinflammatory Mechanisms

Researchers at the Garvan Institute of Medical Research have identified a critical immune system malfunction that drives the rare and potentially fatal disorder known as mevalonate kinase deficiency. For thirty years, the prevailing scientific consensus maintained that immune cells called macrophages were the primary drivers of the intense inflammation associated with the disease. However, according to the study published in the journal Immunity, the actual cause is a defect in natural killer cells, which serve as the body's first line of defense against viral threats. This revelation effectively turns decades of medical dogma on its head and explains why current treatments targeting macrophage signals fail in approximately fifty percent of cases.

The Diagnostic Odyssey of Mevalonate Kinase Deficiency

Mevalonate kinase deficiency, or MKD, is a lifelong autoinflammatory condition characterized by recurring episodes of high fever, joint pain, skin rashes, and severe abdominal inflammation. While only hundreds of cases are officially recorded worldwide, Professor Mike Rogers, a lead author of the study, suggests that many more individuals likely remain undiagnosed. The condition can be life-threatening during severe inflammatory flares, particularly when patients encounter routine infections. By using blood samples from patients and preclinical models, the Australian research team was able to pinpoint exactly where the immune response deviates from its normal path during these episodes.

Identifying the Domino Effect of Misfiring Natural Killer Cells

The research team discovered that in patients with MKD, natural killer cells fail to mature properly and cannot release the toxic granules they typically use to eliminate infected cells. Dr. Marcia Munoz, a lead researcher on the project, explains that when these cells are unable to kill their targets, they remain "trapped" with their ammunition inside. To compensate for this failure, the cells emit an urgent signal for help by pumping out massive quantities of interferon gamma. This powerful inflammatory signal then triggers a secondary reaction in other immune cells, resulting in the dangerous systemic inflammation and high fevers that define the disorder.