Background/Purpose: pSLE and JDM are multisystem inflammatory diseases, whereas juvenile idiopathic arthritis (JIA) is typically an organ-limited disease. “B10 cells”, a rare subset of human B cells with anti-inflammatory properties characterized by their functional capacity to produce IL-10, originate from a progenitor pool (“B10pro cells”) and expand in response to inflammation. We conducted the first pediatric study of B10/B10pro cells with the primary objective of evaluating whether peripheral blood B10/B10pro cell frequencies expand and correlate with disease activity in the 3 most common pediatric autoimmune diseases.

Methods: Following institutional review board approval, pediatric (1-16 years old) subjects with JIA, JDM or pSLE were recruited from the outpatient pediatric rheumatology clinic and the inpatient unit at Duke Children’s Hospital. Subjects with systemic-onset JIA, rituximab therapy within 1 year, current intercurrent illness, or major surgical procedure within 3 months were excluded. For analysis, two groups were defined (JDM/pSLE vs. JIA) and assessed for disease activity (inactive vs. active). After obtaining informed consent, a single blood sample from each subject was analyzed by flow cytometry. B10 and B10+B10pro cell numbers were determined by surface CD19 and intracellular IL-10 staining following ex vivo incubation with lipopolysaccharide (LPS) or CpG oligonucleotides in the absence (5 hour assay measuring B10 cells) or presence (48 hour assay measuring B10+B10pro cells) of recombinant CD40L. A visual analog scale (VAS) score was used to estimate disease activity. Non-parametric tests were used for statistical analysis due to small sample size. B10 and B10+B10pro frequencies were compared using the Mann-Whitney U test. VAS score correlations were performed by Spearman’s rho. Due to multiple comparisons, significance was defined as p<0.01.

Results: 33 patients were recruited, 17 with JIA (8 inactive, 9 active) and 16 with JDM/pSLE (8 inactive, 8 active). No significant differences in the frequencies of B10 or B10+B10pro cells were observed in JIA between active and inactive subjects. Significant differences were observed during disease remission between JIA and JDM/pSLE, with the later group having lower frequencies of B10 (p=0.0003) and B10+B10pro (p=0.0006) cells in response to CpG. Within the JDM/pSLE group, there were significant differences in the frequencies of B10 cells in response to LPS (p=0.0030) and CpG (p=0.0019), and B10+B10pro cells in response to CpG (p=0.0006) between active and inactive subjects. Significant positive correlations with disease activity were observed in the JDM/pSLE group in the B10 responses to LPS (p=0.0034, rho=0.685) and CpG (p=0.0036, rho=0.682), and the B10+B10pro responses to CpG (p=0.000001, rho=0.915).

Conclusion: During disease remission, patients with JDM/pSLE have lower frequencies of B10 and B10+B10pro cells compared to patients with JIA. B10 and B10+B10pro cell frequencies increase with active disease in JDM/pSLE (but not in JIA); the magnitude of this expansion highly correlates with disease activity. Thereby, peripheral blood B10+B10pro cell expansion may represent a novel disease activity marker in patients with JDM/pSLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-interleukin-10-il-10-producing-regulatory-b-cell-b10-cell-compartment-expands-with-disease-activity-in-juvenile-dermatomyositis-jdm-and-pediatric-onset-systemic-lupus-eryth/