Background/Purpose: Adult-onset Still’s disease
(AOSD) is a rare auto-inflammatory disorder.¹ The superimposable
systemic clinical features of AOSD and the pediatric syndrome known as systemic
juvenile idiopathic arthritis (SJIA ) suggest both clinical phenotypes
represent the same disease continuum with different ages of onset. Previous
reports have shown that canakinumab repressed several inflammation- and innate immunity-related
genes, including those in interleukin (IL)-1 signaling pathways in SJIA patients.²
To evaluate if AOSD may be also an IL–1-driven condition, we investigated how
genes that respond to canakinumab in patients with SJIA behave in patients with
active AOSD, relative to healthy subjects.

Methods: For the gene expression analysis, blood
samples were obtained from 17 patients with active AOSD and 19 healthy controls.
Gene expression profiles were compared using Affymetrix U133Plus 2 DNA
microarrays. The probe sets identified in the blood samples of patients with
SJIA were used for supervised visualization of gene expression levels in
untreated patients with AOSD and healthy subjects. The data were
median-centered per gene for clearer visualization of the direction of
differential expression.

Results: An analysis of the average gene regulation
in overall patients showed that genes that were downregulated in patients
with SJIA following canakinumab treatment were upregulated in patients with
active AOSD, relative to healthy subjects (Figure). Comparison of the
gene expression patterns with neutrophil counts showed a correlation between
elevated neutrophil numbers and upregulation of canakinumab-responsive genes. Most
genes that were upregulated following canakinumab treatment in patients with
SJIA were downregulated in a majority of patients with AOSD (Figure).

Figure. Comparison
of gene expression data in patients with Adult Onset Still’s Disease
prior to canakinumab treatment and healthy subjects

Conclusion: The results of this gene expression
analysis are consistent with and further support the concept of a Still’s
disease continuum that includes both pediatric/juvenile (SJIA) and adult (AOSD)
onset of the disease. Genes that respond to canakinumab treatment in patients
with SJIA appear to be inversely dysregulated in those with AOSD. These
findings support further clinical evaluation of anti-IL-1β therapy in
patients with AOSD.

References

¹Martini A.
Ann Rheum Dis 2012;71(9):1437-39.

²Brachat A, et
al. Ann Rheum Dis 2014;73(Suppl2):62.