JIA patients in remission differed genetically from healthy controls
Children with juvenile idiopathic arthritis who were in remission after treatment had a different gene expression compared with healthy controls, according to recent study results.
“What our study shows is that, when children with juvenile idiopathic arthritis achieve remission on medication (defined as 6 continuous months with no disease activity), there are persistent immune abnormalities,” researcher James N. Jarvis, MD, clinical professor and chief, allergy/immunology and rheumatology, department of pediatrics at the University at Buffalo School of Medicine and Biomedical Sciences, told Healio.com.
“The most striking abnormalities are in the innate immune system, something we have long suspected,” Jarvis said. “Thus, although children may be functioning at a completely normal level (in sports, etc.), their completely healthy appearance belies ongoing immunologic perturbation.”
Jarvis and colleagues studied two cohorts. A training cohort included 14 patients with juvenile idiopathic arthritis (JIA; mean age, 8.9 years) who achieved clinical remission on medication (CRM) after use of methotrexate (MTX), 14 children (mean age, 8.9 years) who achieved CRM with MTX plus etanercept (Et) and 15 healthy controls (mean age, 11.5 years). A testing cohort, used to validate training cohort results, included eight JIA patients (mean age, 9.4 years) who achieved CRM with MTX therapy, eight patients with JIA (mean age, 9.6 years) who reached CRM with MTX+Et and eight healthy controls (mean age, 11.1 years).
“RNA was prepared separately from peripheral blood mononuclear cells and granulocytes to identify differentially expressed genes using whole genome microarrays,” the researchers reported. Quantitative, real-time polymerase chain reaction was used to confirm expression results.
Numerous differences in gene expression characterized remission in JIA through MTX or MTX and Et, when compared with healthy controls, showing that remission did not restore immunologic normalcy. Several gene networks that distinguished JIA patients from controls had a hub of steroid hormone receptor superfamily member hepatocyte nuclear factor 4 alpha, according to analysis of differently expressed genes.
“Confocal microscopy … [suggested] a previously unsuspected role for this transcription factor in regulating leukocyte function and therapeutic response in JIA,” the researchers reported.
“These findings provide a framework from which to understand therapeutic response in JIA and, furthermore, may be used to develop strategies to increase the frequency with which remission is achieved in adult forms of rheumatoid arthritis,” the researchers concluded.
Disclosure: The researchers report no relevant financial disclosures.