Cause of lupus and possible way to reverse it discovered

Systemic lupus erythematosus (SLE) is a serious chronic autoimmune disease that particularly affects women and causes different lesions. One of its most common manifestations is kidney damage, known as lupus nephritis. This condition prevented a 15-year-old girl named Uresa from leading a normal life, as she did not respond to available treatments. In June 2023, the young woman, now 16 years old, was treated with CAR-T cell therapy at the University Hospital of Erlangen (Germany) as a last resort to stop the progression of lupus that had deteriorated her kidney function to the point of having to undergo dialysis.

This treatment was unusual, as CAR-T cells had previously been used only to treat haematological cancers such as leukaemia or lymphoma, and in studies with adults suffering from advanced autoimmune diseases. Uresa was the first child with SLE to receive this therapy at the German Centre for Immunotherapy (DZI) at the University Hospital Erlangen. The results of this successful treatment have been published in the medical journal The Lancet.

“Giving CAR-T cells for an autoimmune disease is something special, as it was previously only approved for certain advanced types of cancer,” explains Dr. Tobias Krickau, a Uresa pediatric rheumatologist in the Department of Pediatrics and Adolescent Medicine. With Uresa’s lupus progressing rapidly and not responding to medication, the team decided to try this experimental treatment. The therapy involves extracting some T cells from the patient, modifying them in a lab to equip them with a chimeric antigen receptor (CAR), and then infusing them back into the patient to attack the harmful B cells responsible for lupus.

CAR-T CELLS TO COMBAT AUTOIMMUNE DISEASES

In a clinical trial previously conducted by researchers at the University of Erlangen-Nuremberg, CART-T cells had already been successfully tested in five patients with severe systemic lupus erythematosus and resistance to previous treatments, who experienced a disease remission of up to 17 months following receiving the innovative therapy, according to a study published in Nature Medicine in September 2022.

All five patients showed improvement in symptoms and disappearance of autoantibodies. Rheumatologist Georg Schett, one of the lead researchers, noted that the patients not only improved rapidly, but also lost the autoimmunity associated with lupus, which might mean a long-term cure. The trial also found that CAR-T therapy had mild side effects compared to its use in hematologic cancers, which researchers attributed to the lower B-cell load in lupus patients. No cases of neurotoxicity or serious infections were reported.

Speaking to SMC Spain, Ignacio Melero, professor of Immunology at the University of Navarra, researcher at CIMA and co-director of the Department of Immunology and Immunotherapy at the University of Navarra Clinic, said that although the study of this therapy should be extended to more patients, “the treatment appears reasonably safe in terms of risk-benefit and in these five cases it has proven effective.”

CAR-T THERAPY AS A LAST OPTION AGAINST LUPUS

Uresa’s symptoms began in the fall of 2022 with migraines, fatigue, joint and muscle pain, and the characteristic red butterfly-shaped rash on her face. Despite several treatments with different medications, her condition worsened, especially her kidney function, leading to the need for dialysis. SLE is less common in children than in adults, but it tends to be more aggressive in young people, and current treatments often cause complications and serious side effects.

Dr. Krickau took over Uresa’s treatment in late 2022, starting therapies approved for children to suppress her overactive immune system, but her kidney function continued to deteriorate. Since March 2023, Uresa has spent more time in the hospital than at home, isolated from friends and family, which has taken a toll on her emotional well-being.

With no other treatment options, Dr. Krickau proposed CAR-T therapy – an idea that required extensive preparation and risk assessment. After overcoming numerous organisational and legal hurdles, the Erlangen team succeeded in producing and delivering the CAR-T cells to Uresa. “We initiated CAR-T therapy as part of an extended access programme for severely ill patients,” explains Dr. Krickau.

With information from WebConsultas