Pediatric Year in Review Summarizes Recent Impactful Papers on Basic and Clinical Science

This year’s Pediatric Year in Review at ACR Convergence included new insights in basic and clinical science from dozens of the nearly 2,000 papers in pediatric rheumatology cited in PubMed, starting with a literal look into juvenile idiopathic arthritis (JIA).

“This is the first time we get to see inside the JIA knee,” said Peter Nigrovic, MD, Chief of Immunology at Boston Children’s Hospital, the Prince Turki bin Abdul Aziz al-Saud Chair and Professor of Pediatrics and Medicine at Harvard Medical School, and Director of the Center for Adults with Pediatric Rheumatic Illnesses at Brigham and Women’s Hospital. “(Authors) obtained tissue from the joint as well as peripheral blood and synovial fluid and analyzed these across different axes.”

Recorded sessions at ACR Convergence 2025, including the Pediatric Year in Review, will be available on demand to all registered meeting participants within 72 hours of the live presentation through October 31, 2026, by logging into the meeting website.

Spatial transcriptomics and immunofluorescence helped map cell types and tissue niches throughout the JIA knee to identify differences between JIA and adult rheumatoid arthritis (RA), Dr. Nigrovic noted. Most RA patients, unlike JIA patients, were seropositive. And JIA joints had a specific B cell signature that seems to be unique to pediatric patients.

JIA synovial fluid is enriched in T peripheral helper (Tph) cells, and B cells in JIA synovial fluid are primarily switched memory B cells that have been exposed to an antigen.

“That suggests there is a population of T cells [in synovial fluid)] ready and waiting to help the B cells do something,” Dr. Nigrovic said. “There is evidence for a Tph-to-B cell autoantibody mechanism, especially in early onset JIA.”

Additional basic science developments in pediatric rheumatology include new work on the hemophagocytic lymphohistiocytosis (HLH) immune synapse between T killer cells and target cells that characterized the killing mechanism involving the cytokine interferon-gamma (IFNγ). The immune synapse persists when target cells resist death, resulting in more IFNγ production. Interleukin-18 (IL-18) can increase the kill rate but produces more IFNγ. Target resistance from cancer or other causes can transform the killer cell-target cell pair into an IFNγ generator with impaired killing.

A newly identified gene, dedicator of cytokinesis 8 (DOCK8), is a guanine nucleotide exchange factor involved in multiple immune functions, including macrophage activation syndrome (MAS).

Another study linked Epstein-Barr virus (EBV) infection and cytokine storm syndromes via hyperinflammation. Acute EBV looks like mild MAS, Dr. Nigrovic explained, although the mechanisms are not clear.

A strip of tape may be a new, quick option for taking a skin sample for juvenile dermatomyositis (JDM). Early work suggests that sticking tape to skin, then pulling it off, can produce high IFN and mitochondrial dysfunction scores and other genetic signatures similar to what is achieved through traditional biopsy on lesional or non-lesion skin, Dr. Nigrovic said. Muscle biopsy from JDM patients show similar genetic signatures.

He also reviewed how tissue-specific proteomic signatures can highlight pathways reflecting persistent JDM. These plasma proteins correlate with global disease activity. Chemokine interferon-γ inducible protein 10 kDa (CXCL10) and other biomarkers are on the horizon.

Monogenic diseases have long been a puzzle, starting with the highly variable phenotypes seen between disease carriers. Autosomal random monoallelic expression (aRMAE), the random and durable silencing of one allele, may explain some of the phenotypic variation, Dr. Nigrovic noted.

aRMAE affects about 5% of all genes and correlates with phenotype for inborn errors of immunity responsible for monogenic diseases. Genotype translates to phenotype via the transcriptotype, an individual’s allelic expression. The transcriptotype may represent a novel avenue for treatment, turning active patients into asymptomatic carriers.

Clinical Science

On the clinical side, a new analysis of registry data suggests that cyclophosphamide is not the automatic choice of treatment for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

Rituximab had a similar rate of remission in pediatric patients, 63%, but 22% of rituximab patients were hospitalized versus 10% of cyclophosphamide patients. The median 12-month pediatric vasculitis damage index (pVDI) score was 1 in both groups, and there were no significant differences in the rates of remission, severe adverse events, or organ damage.

“The damage index was very low in both groups,” said Karen Onel, MD, Chief of Pediatric Rheumatology at the Hospital for Special Surgery and Professor of Clinical Pediatrics at Weill Cornell Medical School. “For those of us who remember this disease in the dark ages, we really made great progress in helping these children get well and stay well.”

One of the most important JIA findings of the year was that earlier is better for starting treatment. Early combination therapy with a conventional plus biologic disease-modifying antirheumatic drug (DMARD) beat step-up therapy for clinically inactive disease at three years, 42% versus 35%. Additionally, the odds for the rapid improvement trajectory were improved by starting a DMARD in the first or second month from baseline, Dr. Onel explained,

Patients should expect to remain on therapy for years, she said. New data on deprescribing medication suggested most patients can expect to flare after treatment is withdrawn. A retrospective analysis of DMARD withdrawal in children called discontinuation a Sisyphean endeavor.

“People who are sick enough to go on biologics don’t come off easily,” Dr. Onel said. “Even if they were on methotrexate alone, it was quite challenging to discontinue the drug. Permanent treatment withdrawal is probably not a realistic goal for the therapies that we currently have.”

Discontinuing treatment also affects uveitis relapse. A retrospective multicenter study of adalimumab tapering found that 46% of patients had uveitis relapse. Beginning tapering after at least two years of adalimumab treatment significantly reduced the risk of recurrence. The median time to recurrence was shorter for fast tapering over 10 weeks versus 37 weeks.

Uveitis damage is associated with longer tapering of glucocorticoids and a longer delay in immunosuppressive treatment.

“This has been a banner year for medications in pediatric rheumatology,” Dr. Onel said. “There wasn’t a lot of difference between drugs we used, as long as it was used first. And the side effects were pretty low.”

The U.S. Food and Drug Administration (FDA) approved two new indications using extrapolation of adult data rather than pediatric trials: emapalumab for HLH/MAS, and guselkumab for plaque psoriasis and psoriatic arthritis.

There have also been advances in aggressive treatment.

A second-generation CD19 chimeric antigen receptor (CAR) T cell agent, varnimcabtagene autoleucel, showed progressive long-term improvement in aggressive melanoma differentiation-associated gene 5 antibody-positive dermatomyositis associated rapidly progressive interstitial lung disease (MDA5+ DM-RPILD) without immunosuppression, Dr. Onel noted.

Stem cell transplantation produced complete response in nine children with sJIA-LD. Another four patients died from transplant-associated complications.

When it comes to interacting with patients, potential patients, and their families, pediatric rheumatologists are active on social media, but most content creators, 76.8%, are not health professionals. Pediatric rheumatology content in the 150 most popular posts on Facebook, Instagram, and TikTok accounted for 37.6 million interactions and 520.8 million views, Dr. Onel shared.

“We might be making better content, but it’s obviously less fun content,” she said. “We have to make it fun.”