Changes in red blood cells contribute to lupus

Mitochondria (marked with anti-COXIV antibody) can be detected in lupus red blood cells (marked with Band 3 antibody), but not in healthy red blood cells.Credit: Cornell University

According to a study led by researchers at Weil Cornell Medicine, the autoimmune disease lupus can be caused by a faulty process in the development of red blood cells (RBCs). This discovery could lead to new ways to classify and treat patients with the disease.

Researchers who released the survey results on Aug. 11 found that in many lupus patients, mature red blood cells were unable to remove mitochondria. This is a small molecular reactor that helps most cell types convert oxygen into chemical energy, but is usually excluded from red blood cells.

This abnormal retention of mitochondria can cause a cascade of inappropriate and harmful immune activity that is characteristic of the disease.

“Our results confirm that red blood cells can play a very important role in promoting inflammation in a subset of lupus patients,” said the Gale and Iradrkiel Institute for Pediatric Health and Ronemen Shell. Dr. Virginia Pasqual, senior writer and director of Dolkiel, said. Professor of Pediatrics at Weil Cornell Medicine. “Therefore, we can add new pieces to the lupus puzzle and open the door to new possibilities for therapeutic interventions.”

The lead author of this study was Dr. Simone Caielli, Assistant Professor of Pediatric Immunology Research at the Drukier Institute and Weill Cornell Medicine.

Lupus, also known as systemic lupus erythematosus, is a chronic condition characterized by intermittent and sometimes debilitating seizures. Immune system It acts on the body’s own healthy tissues such as skin, joints, hair follicles, heart and kidneys. A common underlying factor is abnormally increased production of an immune stimulating protein called type I interferon.

Treatments, which are often used over a long period of time and have side effects, aim to suppress immune activity, such as inflammation caused by interferon. There is no cure for lupus, and how it occurs is still largely a mystery. It is estimated that it affects around 200,000 people in the United States, most of whom are women.

Previous studies have shown mitochondrial defects in the immune cells of lupus patients. In a new study, the researchers looked at red blood cells that appear to be completely free of mitochondria. They found that many lupus patients had red blood cells with detectable mitochondria – and these cells were especially common in those with the most severe lupus symptoms. In contrast, healthy controls lacked red blood cells, including mitochondria.

Later, Kaieri in previous studies looked at mitochondria mainly in mice, how to normally remove mitochondria when human red blood cells mature, and why this process is flawed in patients with lupus. I studied.

Further experiments have shown how these abnormal red blood cells cause inflammation. Generally, red blood cells are cleared out by immune cells called macrophages as they age or show signs of damage. Antibodies that bind to red blood cells also make it easier to remove them.

When taken up by macrophages, the mitochondrial DNA of the erythrocytes stimulates a potent inflammatory pathway called the cGAS / STING pathway to stimulate the production of type I interferon. Emphasizing the relevance of these results, “Lupus patients with evidence of anti-RBC antibodies circulating with red blood cells, including mitochondria, had a higher interferon signature than those who did not,” Kaieri said. ..

Researchers are currently studying the complex processes by which mitochondria are preserved. Red blood cells and it will cause abnormal immune activation. Identifying patients who have lupus symptoms in this way can help identify when they are likely to develop lupus. Lupus To identify flares and specific treatments for them.

Platelets can play an important role in the development of lupus

For more informations:
Simone Caielli et al., Erythrocyte Mitochondrial Retention Induces Bone Marrow Dependent Type I Interferon in Human SLE. Cell (2021). DOI: 10.1016 / j.cell.2021.07.021

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Cornell University

Quote: Red blood cell changes were retrieved from https://medicalxpress.com/news/2021-08-red-blood-cell-contribute-lupus.html on August 11, 2021 (August 11, 2021)

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