October 7, 2024 —

A groundbreaking study partly funded by the Lupus Research Alliance (LRA), published in Immunity, uncovered an unexpected contributor to inflammation in lupus.

Led by Drs. Virginia Pascual and Simone Caielli from Weill Cornell Medical College, the research identified a specific subset of monocytes (a type of immune cell) that release an inflammatory protein called IL-1β. This occurs when these monocytes ingest red blood cells containing mitochondria (small structures in a cell that generate energy). Mitochondria-containing red blood cells are an abnormal type of red blood cell previously identified by the same team in children with systemic lupus erythematosus (SLE) (Caielli et al., Cell, 2021).

“This study offers a new view on both potential biomarkers and therapies to treat SLE, a disease where so many therapeutic approaches have failed,” said Dr. Pascual. The study was supported by Dr. Caielli’s 2020 LRA Lupus Innovation Award. Dr. Pascual was previously awarded the LRA’s 2017 Lupus Insight Prize and 2021 Global Team Science Award.

Lupus-related inflammation is often driven by molecules called type I interferons, but blocking these molecules doesn’t fully alleviate symptoms, indicating other factors are involved. The researchers discovered that in children with SLE, monocytes not only produce interferons but also IL-1β, a powerful inflammatory molecule not previously associated with lupus. The presence of these dual-producing monocytes was linked to the severity of the disease, suggesting they could be a useful marker for tracking lupus activity.

They also discovered that the release of IL-1β from these dual-producing monocytes is regulated by a protein called MxA, which enables IL-1β to exit the cell without causing cell death.

“It was exciting for us to confirm how studying children with SLE can provide new insights into the novel inflammatory mechanisms driving this complex disease,” said Dr. Caielli.

Weill Cornell Medicine Press Release