Anomalies in the number of immune cells and specific cellular signals are both linked to the severity of systemic juvenile idiopathic arthritis (JIA) symptoms, researchers in China found.

According to a study published in the journal Joint Bone Spine, these findings add new knowledge to the underlying processes regulating the clinical features of the disease. Also, recognizing this immune imbalance may help clinicians diagnose systemic JIA.

Juvenile arthritis, or JA, is often called idiopathic (JIA) because its cause is unknown.

The study is titled “Decreased PD-1 expression on circulating CD4+T cell and PD-L1 expression on myeloid dendritic cells correlate with clinical manifestations in systemic juvenile idiopathic arthritis.”

Systemic juvenile arthritis is an autoimmune disorder that accounts for about 10 percent of juvenile arthritis cases. Although rare, systemic JIA is associated with a poor outcome and is directly responsible for more than two-thirds of JIA patient deaths.

Besides joint inflammation, this disorder is also characterized by systemic symptoms, which include persistent and recurrent fever, lymph node enlargement, a temporary rash, and an enlarged liver and spleen.

To better understand which immune factors could contribute to systemic JIA, the research team examined 101 children with different JIA subtypes and 50 healthy volunteers, followed at Shanghai Children’s Medical Center in China.

The patients included 41 children with polyarthritis, 30 with enthesitis-related arthritis (ERA), and 30 with systemic JIA. They were also classified as having active disease (moderate or high disease activity) or inactive disease (mild disease activity or inactivity).

First, the team analyzed the numbers of immune cells and found that systemic JIA patients had significantly fewer T-cells positive for the CD4 marker (CD4+ T-cells) compared to other patients or healthy controls. CD4+ T-cells play a major role in initiating and shaping the immune response.

Also, patients with active disease were found to have the least amount of CD4+ T-cells. These patients also had significantly more myeloid dendritic cells, which are important regulators of autoimmune response, than any other group of patients and controls in the study.

Next, researchers looked at the levels of PD-1 and PD-L1 surface proteins. These proteins are involved in the interaction of dendritic cells and T-cells, preventing the activation of an immune response.

These levels of these inhibitory signals were lower in patients with active systemic JIA. Their CD4+ T-cells were found to have reduced levels of PD-1, and their myeloid dendritic cells had lower PD-L1 levels.

These findings suggest that fewer PD-1 and PD-L1 signals might contribute to disease development.

Indeed, a low percentage of the protein PD-1 in CD4+ T-cells was found to be linked to higher disease activity as measured by the 27-joint Juvenile Arthritis Disease Activity Score (JADAS-27) and the number of involved joints.

Also, a low percentage of PD-L1 in myeloid dendritic cells was found to be correlated with higher disease activity scores and the development of fever.

“In summary, for the first time we have observed decreased CD4⁺ T-cell and increased [myeloid dendritic cells] and corresponding reduced PD-1/PD-L1 expression in active [systemic JIA] patients,” the researchers wrote.

The team believes that recognizing immune responses in JIA may be helpful for the differential diagnosis of its subtypes and for identifying the processes “responsible for distinct clinical manifestations.”