January 31, 2018
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Switched memory B cell expansion faster in juvenile arthritis

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Angela Aquilani
Emiliano Marasco

The expansion of switched memory B cells is faster among patients with juvenile idiopathic arthritis compared with healthy children, and the effect is particularly evident in children with early-onset disease, according to findings published in Arthritis and Rheumatology.

“This study is important because it identifies the B-cell compartment of the immune system as a crucial player in the development of oligoarticular and polyarticular [juvenile idiopathic arthritis], allowing us to better dissect the mechanisms of development of these forms of [juvenile idiopathic arthritis],” Emiliano Marasco, MD, and Angela Aquilani, MD, both of the Bambino Gesù Pediatric Hospital, in Rome, told Healio Rheumatology. “Moreover, it lays the groundwork for implementing B cells as biomarkers of disease activity and response to treatment.”

To study abnormalities in B-cell populations in children with juvenile idiopathic arthritis (JIA), the researchers enrolled 109 patients with oligoarticular and polyarticular JIA. Among the participants, the researchers followed 17 who were receiving methotrexate alone, and 33 who were treated with methotrexate in addition to a TNF inhibitor, for a median of 11.2 months. B-cell subsets were measured at the first and last visits of follow-up.

The researchers analyzed B-cell subsets in peripheral blood and synovial fluid using flow cytometry.

According to the researchers, switched memory B cells were significantly increased among patients with JIA, compared to their healthy peers (P < .0001). In addition, patients with early-onset disease — at less than 6 years — experienced greater expansion in switched memory B cells than those with late-onset JIA. That greater expansion among early-onset patients persisted throughout the course of the disease.

In longitudinal studies, the number of switched memory B cells increased significantly during methotrexate treatment, regardless of the presence of active or inactive disease. Patients who received methotrexate in addition to a TNF inhibitor and maintained remission, experienced a switched memory B cell increase that was significantly lower (P = .004) than in patients who experienced active disease. According to the researchers, TNF inhibitors reduced the expanded switched memory B cells only in children who had responded to treatment and achieved a good control of the disease.

“Our work describes abnormalities in B-cell subpopulations in children with oligoarticular and polyarticular JIA,” Marasco and Aquilani said. “Firstly, this provides a biological ground to separate oligoarticular and polyarticular JIA from, for example, systemic JIA and psoriatic JIA where, respectively, the innate immune system and T cells are thought to play a central role. Secondly, we observed that in patients responding to treatment, TNF inhibitors are able to correct the expansion in memory B cells observed in JIA patients, making these cells a promising biomarker.” – by Jason Laday

Disclosure: The researchers report grant funding from Ricerca Corrente, of the Ministero della Salute. See the full study for additional authors’ disclosures.