Year in Review Covers Cutting-Edge Research in Pediatric Rheumatology

In the past year, researchers have made several critical breakthroughs with clinical, basic, and translational research in pediatric rheumatology. Led by two experts in the field, the Pediatric Year in Review provided an update on recent significant contributions to the literature.

This session is available on demand for registered ACR Convergence 2023 participants through Oct. 31, 2024, on the meeting website.

Hanna Kim, MD, MS, Assistant Clinical Investigator at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), delivered this year’s basic science research review. Among the publications she cited was a recent paper on research into the role of CD14+ monocyte-derived oxidized mitochondrial DNA in the inflammatory interferon (IFN) type 1 signature in juvenile dermatomyositis (JDM).

Analyzing JDM monocytes, researchers found decreased mitochondrial gene expression with higher levels of oxidative stress and production of oxidized mitochondrial DNA (Ox-mtDNA). Ox-mtDNA was associated with increased IFN-stimulated gene expression, which was ultimately suppressed using N-acetylcysteine (NAC), toll-like receptor 9 (TLR9) antagonists, and cyclic GMP-AMP synthase (cGAS) inhibitors. Dr. Kim noted that additional research targeting mitochondrial biology may yield further discoveries with JDM’s pathologic IFN signature.

She also discussed new findings related to type 1 IFN signature and cycling lymphocytes in macrophage activation syndrome (MAS) that compared MAS to systemic juvenile idiopathic arthritis (SJIA) and Still’s disease (SD) using bulk RNA-seq and single-cell RNA-seq.

“The top two most different things between MAS and active SD are type 1 and type 2 IFN,” Dr. Kim explained. “So, they looked at type 1 and type 2 IFN-specific scores, and they found that both type 1 and type 2 scores are increased in MAS.”

Researchers found that increased type 1 IFN, along with elevated levels of interleukin-15 (IL-15), in MAS can synergistically increase the generation of CD38+HLA-DR+ lymphocytes. Dr. Kim noted that Janus kinase (JAK) inhibitors showed promise in mitigating this response.

Stacy Ardoin, MD, MSc, Assistant Professor at The Ohio State University, presented the clinical research review. She noted several important updates in practice guidance related to vaccines, including the ACR’s 2022 Guideline for Vaccinations in Patients with Rheumatic and Musculoskeletal Diseases.

The updated guideline recommends withholding the use of methotrexate in pediatric patients for two weeks after receiving the influenza vaccine. It also suggests that while the flu vaccine is safe to administer, pediatric patients should wait until six months after the use of rituximab before receiving other non-live vaccines. The ACR guideline also stipulates that infants exposed in utero to tumor necrosis factor (TNF) inhibitors should be given the rotavirus vaccine in their first six months.

Dr. Ardoin also discussed the prevalence of mental health issues in pediatric patients potentially related to the presence of rheumatic diseases, and referenced a paper that examined the incidence and accumulated burden of psychiatric disorders in juvenile idiopathic arthritis (JIA) relative to the general population and their same-sex siblings. Investigators found that compared to the general population, the risk of psychiatric disorders, including suicidal behavior, increased in patients with JIA.

Another mental health study, from Canada, evaluated the high rates of depression and anxiety symptoms in adolescents with JIA using the Revised Child Anxiety and Depression Scale. The results showed that 24% of respondents reported struggling with a major depressive disorder, while 22% struggled with a panic disorder.

“Both of these studies really demonstrate that mental health disorders are prevalent in probably most of our conditions, including JIA, and really underscore the need for more work in our community to ensure these patients are aptly cared for,” Dr. Ardoin said.