High neutrophil counts observed at the onset of systemic-onset juvenile idiopathic arthritis (JIA) decreased dramatically after initiation of recombinant interleukin-1 (IL-1) receptor agonist therapy, according to the results of a prospective cohort study published in Arthritis & Rheumatology. The results suggest that neutrophils play an important role in the early inflammatory phase of systemic-onset JIA.
Investigators from the University Medical Center Utrecht, The Netherlands, analyzed data from 50 patients with systemic-onset JIA who were being treated with a recombinant IL-1 receptor antagonist at disease onset and during remission. Treatment was initiated with 2 mg/kg per day subcutaneously after failure of nonsteroidal anti-inflammatory drugs (NSAIDs). When clinically inactive disease was achieved, recombinant IL-1 receptor antagonist therapy was tapered off after 3 months. Patients with persistent symptoms received corticosteroids in addition to the treatment regimen. If that therapy failed, patients were then switched to an alternative biologic agent. Serum obtained from patients with systemic-onset JIA was used to assess circulating levels of neutrophil-related proteins using multiplex immunoassay.
Neutrophil counts were increased at disease onset, correlated with levels of inflammatory mediators, and normalized within days following initiation of recombinant IL-1 receptor antagonist therapy. A substantial upregulation of inflammatory processes in neutrophils from patients with active systemic-onset JIA was detected by RNA sequencing, overlapping significantly with the transcriptome of sepsis. Neutrophils in participants with active systemic-onset JIA displayed a primed phenotype characterized by increased production of reactive oxygen species, CD62L shedding, and secretory vesicle degranulation, which was reversed during remission on recombinant IL-1 receptor antagonist therapy.
Participants with a short duration of disease had high neutrophil counts, more immature neutrophils, and a complete response to recombinant IL-1 receptor antagonist therapy, whereas those experiencing symptoms for >1 month had normal neutrophil counts and an unsatisfactory response to therapy.
The investigators concluded that the use of IL-1 blockade in patients with systemic-onset JIA helps to revert primed neutrophils that display sepsis-like features.
Ter Haar NM, Tak T, Mokry M, et al. Neutrophils in systemic onset juvenile idiopathic arthritis display sepsis-like features which can be reverted by IL-1 blockade [published online February 9, 2018]. Arthritis Rheumatol. doi:10.1002/art.40442