Youthful Exuberance: The Year in Review for Pediatric Rheumatology

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WASHINGTON, D.C.—It is no small task to summarize an entire year’s worth of research accomplishments in any field of medicine, let alone one as complex as rheumatology. At ACR Convergence 2024, the Pediatric Year in Review not only provided a thoughtful summary, but also grouped advances along several different themes.

Immune Health & More

Dr. Turnier

Jessica Turnier, MD, MS, assistant professor of pediatric rheumatology, University of Michigan, Saline, began her talk by discussing new tools being used to study immune health.

One article by Sparks and colleagues was meant to provide an understanding of what constitutes a healthy immune system rather than what causes immune system dysregulation. By looking at transcriptomics, serum protein, peripheral immune cell frequency and clinical data from more than 220 patients with 22 different monogenic conditions, along with 42 age- and sex-matched healthy controls, Sparks and colleagues were able to use multiple approaches (e.g., supervised machine learning and an unsupervised approach) to converge on a unified immune health metric (IHM). Dr. Turnier explained that this IHM holds promise as a biomarker of disease activity or treatment response because it is lower in patients with high disease activity, vs. low disease activity, in pediatric systemic lupus erythematosus, and it is higher in patients with rheumatoid arthritis who responded to treatment than in those who did not.¹

In a different study, Cui and colleagues sought to develop an immune dictionary to understand cell-type response to various cytokines using a murine model. This immune dictionary, which comprises single-cell transcriptomic profiles of more than 17 immune cell types in response to 86 different cytokines, can now be used to: 1) generate new hypotheses for cytokine functions; 2) illuminate pleiotropic effects of cytokines; 3) provide information about the activation states of each immune cell type; and 4) provide a framework to deduce the roles of specific cytokines in immune responses.²

The Pathogenesis of Disease

Dr. Turnier next discussed studies describing new mechanisms in the pathogenesis of rheumatic disease. The first study, by Bodansky and colleagues, looked at the link between SARS-CoV-2 infection and the development of multi-system inflammatory syndrome in children (MIS-C), a rare but serious condition that can manifest with features that look very much like toxic shock syndrome of Kawasaki disease.

In this study, the authors compared proteome-wide autoantibody profiles in nearly 200 children with MIS-C with those from 45 children convalescing after asymptomatic or mild SARS-CoV-2 infection. They found that children with MIS-C have distinct autoantibodies to the autoantigen sorting nexin 8 (SNX8) and a specific region of the SARS-CoV-2 nucleocapsid (MADS). They also found that these children have cross-reactive CD8+ T cells that bind both SNX8 and MADS, thereby implying that MIS-C is associated with these cross-reactive autoantibodies and the T cell response to them.³