Polyclonal expansion of TCR Vbeta 21.3+ CD4+ and CD8+ T cells is a hallmark of Multisystem Inflammatory Syndrome in Children.

Multiple Inflammatory Syndrome in Children (MIS-C) is a delayed and severe complication of SARS-CoV-2 infection that strikes previously healthy children. As MIS-C combines clinical features of Kawasaki disease and Toxic Shock Syndrome (TSS), we aimed to compare the immunological profile of pediatric patients with these different conditions. We analyzed blood cytokine expression, and the T cell repertoire and phenotype in 36 MIS-C cases, which were compared to 16 KD, 58 TSS, and 42 COVID-19 cases. We observed an increase of serum inflammatory cytokines (IL-6, IL-10, IL-18, TNF-α, IFNγ, CD25s, MCP1, IL-1RA) in MIS-C, TSS and KD, contrasting with low expression of HLA-DR in monocytes. We detected a specific expansion of activated T cells expressing the Vß21.3 T cell receptor ß chain variable region in both CD4 and CD8 subsets in 75% of MIS-C patients and not in any patient with TSS, KD, or acute COVID-19; this correlated with the cytokine storm detected. The T cell repertoire returned to baseline within weeks after MIS-C resolution. Vß21.3+ T cells from MIS-C patients expressed high levels of HLA-DR, CD38 and CX3CR1 but had weak responses to SARS-CoV-2 peptides in vitro. Consistently, the T cell expansion was not associated with specific classical HLA alleles. Thus, our data suggested that MIS-C is characterized by a polyclonal Vß21.3 T cell expansion not directed against SARS-CoV-2 antigenic peptides, which is not seen in KD, TSS and acute COVID-19.

Review: Neonatal dialysis is technically feasible but ethical and global issues need to be addressed.

AIM: Our aim was to look at the technical, ethical and global issues related to neonatal dialysis. METHODS: We performed a PubMed research on manuscripts published from March 2010 to March 2020 and retrospectively reviewed all neonates who received dialysis in our French paediatric and neonatal intensive care units from April 2009 to March 2019. RESULTS: Dialysis is performed on neonates with pre-existing renal diseases, acute kidney injuries or inborn errors of metabolism. It is required in 0.5%-1% of neonates admitted to the neonatal intensive care units. Peritoneal dialysis and extracorporeal blood purification are both feasible, with more complications, but the results are close to those obtained in older infants, at least in children without multi-organ dysfunction. Novel haemodialysis machines are being evaluated. Ethical issues are a major concern. Multidisciplinary teams should consider associated comorbidities, risks of permanent end-stage renal disease and provide parents with full and neutral information. These should drive decisions about whether dialysis is in child's best interests. CONCLUSION: Neonatal dialysis is technically feasible, but ethically challenging, and short-term and long-term data remain limited. Prospective studies and dialysis registries would improve global management and quality of life of these patients at risk of chronic kidney disease.