Lupus Patients Shared Immune Cell Abnormality: 33 of 34 Showed It

An unexpected immune signal

Researchers at the La Jolla Institute for Immunology and the University of Washington examined RNA-splicing errors previously identified in neutrophils from people with lupus. These errors can join genetic-instruction segments incorrectly before cells use them to make proteins.

When cells read the altered instructions, they may produce unusual peptides—short chains of amino acids. The researchers found evidence that T cells and antibody-producing B cells could recognize these molecules, potentially contributing to lupus-related inflammation and tissue damage.

How the study developed

The work brought together Tomas Mustelin’s laboratory at the University of Washington School of Medicine and Stephen Schoenberger’s research group at the La Jolla Institute for Immunology. Mustelin’s team had observed unusually frequent splicing errors in neutrophils from lupus patients; Schoenberger investigated whether the errors could generate molecules that provoke an immune response.

A different view of autoimmunity

Lupus is a chronic autoimmune disease that can damage joints, skin, kidneys and other organs. Scientists have sought to understand why T cells and B cells attack the body’s own tissues.

One longstanding explanation is that immune tolerance—the safeguards that normally prevent attacks on healthy tissue—breaks down. Schoenberger proposed another possibility: immune cells may be responding as designed to molecules they perceive as foreign, alongside danger signals from inflammation.