HLA-DRB1*15 and Eosinophilia Are Common Among Patients With Systemic Juvenile Idiopathic Arthritis

Area of Science:

• Rheumatology
• Immunogenetics
• Pulmonology

Background:

• Systemic juvenile idiopathic arthritis (JIA) treatment with interleukin (IL)-1 and IL-6 blockers raises concerns for adverse drug reactions and lung disease (systemic JIA-LD).
• The HLA-DRB1*15 genotype has been implicated as a potential risk factor for adverse drug reactions in systemic JIA patients.

Purpose of the Study:

• To investigate the association between HLA-DRB1*15 carriage, IL-1/IL-6 blocker use, and the development of systemic JIA-LD.
• To evaluate the role of eosinophilia as a potential biomarker for adverse drug reactions and systemic JIA-LD.

Main Methods:

• Retrospective chart review of 86 systemic JIA patients treated between 1996 and 2022.
• HLA typing performed on 23 patients.
• Comparison of clinical characteristics, including HLA-DRB1*15 status, eosinophilia, and systemic JIA-LD, between patient subgroups.

Main Results:

• HLA-DRB1*15 carriage was prevalent (74%) in the HLA-typed cohort and strongly associated with systemic JIA-LD (all 7 patients with JIA-LD carried DRB1*15).
• Eosinophilia occurred in 39% of systemic JIA patients, often preceding IL-1/IL-6 blockade, and was linked to adverse drug reactions and macrophage activation syndrome.
• Patients with systemic JIA-LD were younger at diagnosis and more likely to have had macrophage activation syndrome.

Conclusions:

• HLA-DRB1*15 carriage is more common in systemic JIA patients and significantly associated with systemic JIA-LD.
• Eosinophilia and systemic JIA-LD are more frequent in severe systemic JIA cases complicated by macrophage activation syndrome.
• The findings highlight potential genetic and clinical risk factors for adverse outcomes in systemic JIA treated with targeted therapies.