By Marie Rosenthal
Intravenous immune globulin (IVIG)—a common treatment for multisystem inflammatory syndrome in children (MIS-C)—likely works by depleting neutrophils, according to a recent study from the University of California, San Diego.
The researchers also found that IVIG works in a similar manner for treating Kawasaki disease (KD), another rare inflammatory condition that affects children and shares symptoms with MIS-C (J Clin Invest 2021;131[20]:e147076).
MIS-C is a rare condition that usually affects school-age children who initially had only mild COVID-19 symptoms or no symptoms at all. As of Oct. 18, a total of 5,217 children have met the case definition of MIS-C and 46 have died, according to the CDC.
MIS-C is marked by severe inflammation of two or more parts of the body, including the heart, lungs, kidneys, brain, skin, eyes and gastrointestinal organs. Because symptoms overlap with KD, treatments for MIS-C are guided in part by what is known about treating KD. IVIG is a common and effective treatment for cardiac complications caused by KD. For patients with MIS-C, however, IVIG alone does not always resolve symptoms, and health care providers may need to prescribe additional anti-inflammatory drugs.
To better understand how IVIG works in children with MIS-C, researchers led by Ben A. Croker, PhD, and Jane C. Burns, MD, from the UC San Diego School of Medicine, profiled immune cells from patients with MIS-C or KD. The team sampled cells before treatment began as well as two to six weeks after patients received IVIG.
The researchers found that neutrophils from these patients were highly activated and a major source of interleukin-1beta, which is one driver of inflammation in the body. After IVIG treatment, these activated neutrophils were significantly depleted in patients with MIS-C or KD.
According to the researchers, their findings are the first to explain why IVIG is effective for both conditions. However, more work is needed to understand how IVIG causes apoptosis in these activated neutrophils and why certain patients with MIS-C require additional anti-inflammatory treatments.
Overall, the research will help health care providers as they determine the most effective methods to treat patients with MIS-C.
The study was funded by the National Institute of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute; and the National Institute of General Medical Sciences. The work is supported by the NIH’s CARING for Children with COVID, PreVAIL kIds and RADxSM-rad research programs.
In related news, researchers at Children’s Hospital Colorado found that adding infliximab, a monoclonal antibody used in a number of autoimmune diseases, to IVIG in patients with MIS-C improved cardiac outcomes (Pediatrics 2021 Sep 20. doi:10.1542/peds.2021-052702).
In addition, those patients had a decreased need for additional therapies, decreased ICU length of stay, decreased development of left ventricular dysfunction and more rapid resolution of inflammation. Infliximab is a medication often used to treat autoimmune diseases.
As a result of the improved outcomes associated with IVIG plus infliximab, Children’s Colorado has updated its MIS-C care pathway to recommend administration of intensified initial therapy (IVIG plus infliximab) for all patients highly suspected of or diagnosed with MIS-C.
“While further randomized controlled trials are necessary to confirm these findings, the demonstrated improvement in cardiac and other outcomes associated with IVIG plus infliximab made it imperative that we share this updated clinical pathway as quickly as possible,” said Sam Dominguez, MD, PhD, an infectious disease specialist at Children’s Colorado, in Aurora, and a co-author of the study.
The research is based on a retrospective cohort study of 72 pediatric MIS-C patients comparing outcomes of those who received an initial treatment of IVIG alone with those who received initial treatment with IVIG plus infliximab.
“Children’s Colorado has extensive experience in treating high-risk Kawasaki disease patients with IVIG plus infliximab, which reduces the need for additional therapies and the duration of treatment,” said Pei-Ni Jone, MD, a cardiologist and the director of the Kawasaki Disease Clinic at Children’s Colorado. “All MIS-C patients at Children’s Colorado, who are typically more ill than KD patients, are now being treated with an initial dual therapy to improve overall outcomes.”
