German scientists have discovered that children with classic autoinflammatory systemic juvenile idiopathic arthritis (sJIA) or chronic polyarticular sJIA have different molecular signatures that can be used to distinguish them.
Researchers are hopeful that in the future, these molecular biomarkers may be used to hasten diagnosis and aid physicians in selecting the best course of treatment for each child.
The study, “Molecular signature characterisation of different inflammatory phenotypes of systemic juvenile idiopathic arthritis,” was published in Annals of the Rheumatic Diseases.
sJIA is the most severe type of juvenile arthritis (JIA) and is characterized by widespread tissue inflammation that not only affects patients’ joints, but also organs and glands.
Recent studies have suggested that sJIA has two different phases: an early phase characterized by fever and systemic inflammation, with minor or no joint disease (classic autoinflammatory sJIA, or sJIAsyst); and a later phase characterized by chronic joint disease (chronic polyarticular sJIA, or sJIApoly).
In some cases, when the disease is rapidly identified, treat-to-target strategies may be used to stop disease progression, allowing patients to go into clinical remission. However, the absence of telltale signs of joint disease at the early stages of the disorder may, in some cases, delay the diagnosis.
“Early in disease, arthritis is minimal or absent, which complicates establishing the diagnosis when features also fitting differential diagnoses such as infections dominate,” researchers said.
“Early diagnosis and recognition of [symptoms shown] could therefore be key to initiate effective treat-to-target-based management strategies during a window of opportunity and also to prevent the progression of sJIA into a more aggressive chronic arthritis phenotype. There is an unmet need for laboratory tests to diagnose and monitor sJIA disease activity,” they said.
Researchers from the University of Münster in Germany and collaborators now set out to identify new molecular biomarkers that could be used to distinguish children at different stages of sJIA.
The study included two groups: a discovery group composed of 30 children (10 with sJIAsyst, 10 with sJIApoly and 10 with infections); and a verification group composed of 106 children (45 with sJIAsyst, 29 with sJIApoly and 32 with infections).
Serum samples from children in the discovery group were used to screen potential molecular biomarkers, while samples from children in the verification group were used to validate biomarker candidates previously identified in the discovery group.
Initial screenings identified 72 proteins whose levels were different among the three sets of children in the verification group. These included 41 proteins whose levels were different between children with sJIAsyst and children with sJIApoly , and 31 between children with sJIAsyst and children with infections.
From the 72 biomarker candidates identified, 48 were chosen to be validated. The top 30 biomarker candidates successfully distinguished 91% of children with sJIAsyst from children with sJIApoly , and 77% of children with sJIAsyst from children with infections.
“The identified protein signature of sJIA versus infections can help to establish an early diagnosis. The discrimination of SJIA [subtypes] may improve the understanding of the [disease mechanisms] underlying different disease phases and courses, which may inform future treat-to-target strategies,” the investigators stated.
“Future work could include biomarker measurements at specific time points, including at diagnosis and flare as well as in established phenotype switches in a larger cohort,” they said.