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Children with MIS-C have a highly activated immune system, studies find

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Researchers at the Philadelphia Children’s Hospital (CHOP) and the University of Pennsylvania’s Perelman School of Medicine have first digged deeper into how the immune system behaves in patients with pediatric multisystem inflammatory syndrome (MIS-C). The system is highly activated and in many respects resembles the adult immune system of severe COVID-19.

The results were published today Scientific immunochemistryA better understanding of immune activation in MIS-C patients has shown that not only can they help treat those patients better, but they can also improve the treatment of adults with severe COVID-19. I will.

This study shows that children with MIS-C are highly immunostimulated, especially for CD8. T cellsHowever, this activation subsides when the patient begins to improve clinically. Our findings provide a broad immunological basis for understanding the etiology and recovery of this new SARS-CoV-2 associated inflammatory syndrome and may affect adult diseases. “

Laura Vella, MD, PhD, Ph.D., Lead Author of Infectious Diseases Division and Study of CHOP

Pediatricians first recognized MIS-C in April 2020, when pediatric patients began to exhibit hyperinflammatory symptoms such as fever, gastrointestinal disorders, and cardiogenic shock. This syndrome, which is thought to be a post-infection complication of SARS-CoV-2 infection, has similar clinical symptoms to Kawasaki disease, especially vascular lesions, but is unique to Kawasaki disease in clinical and inflammation. sex, Autoantibodies signature. This syndrome also lacks the respiratory complications typical of COVID-19 in adults and children. However, until this point, the immunological characteristics driving MIS-C were not well understood.

To better understand the immunology behind MIS-C, researchers took blood samples from patients admitted to CHOP with COVID-19 or MIS-C between April and June 2020. Collected. They analyzed more than 200 immune parameters, including serological and plasma cytokine data. These data were then compared to samples from adult COVID-19 patients, recovered adult COVID-19 subjects, and healthy adults.

Researchers have found that children with MIS-C have highly elevated T cells, especially CD8 T cells, and that a subset of vascular patrol CD8 T cells is highly activated. These vascular patrol CD8 T cells have a proposed role in controlling the persistence or reactivation of viral infections and are also involved in cardiovascular disease that may be associated with the vascular symptoms observed in these patients. I will. Researchers have found patients with MIS-C who are all high in vascular patrol CD8 T cells, need support for vascular action, have elevated D-dimer, and have decreased platelets. Elevation of CD8 T cells far exceeded that observed by researchers in pediatric patients with acute COVID-19 and most adults with COVID-19, but with clinical improvement, CD8 T cells in MIS-C patients Level has dropped.

The study also highlighted a biased B-cell response in MIS-C patients compared to acute pediatric COVID-19 and resolved adult diseases. Patients with MIS-C are almost universally seropositive for SARS-CoV-2, which means that sufficient time has passed for antiviral antibodies to develop and be detected from the infection. To do. Pediatric and adult patients with acute COVID-19 are not seropositive, consistent with the belief that MIS-C is a delayed event after SARS-CoV-2 infection. Despite MIS-C being a delayed event, researchers have found that plasma cells in MIS-C patients are elevated or immature B cells, whereas adults recover from COVID-19. Plasma cells were found to return to baseline 2-3 weeks after the symptoms disappeared. A subset of adult patients admitted with COVID-19 showed a sustained increase in plasma cells.

Researchers have proposed three possible drivers of immune etiology in MIS-C: (1) continuous activation of adaptive immune responses driven by sustained SARS-CoV-2. antigen(2) Additional triggers such as viruses or secondary infections localized to new tissue types that occur 2-3 weeks after the initial infection with SARS-CoV-2. Or (3) autoimmune reaction. Further research is needed to investigate these potential scenarios.

“SARS-CoV2 infections can lead to widespread clinical and immunological outcomes,” said Dr. E. John Welly, director of the Institute of Immunology and senior author of the study. “The use of the’immune health’profiling approach for pediatric COVID-19 patients not only identified distinct features of pediatric MIS-C symptoms, but the insights gained by studying MIS-C patients are pediatric and Adult COVID-19 patients. “

Source:

Journal reference:

Bella, LA, et al. (2021) Deep immune profiling of MIS-C shows marked but transient immune activation compared to adult and pediatric COVID-19. Scientific immunochemistry.. doi.org/10.1126/sciimmunol.abf7570..

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