Inflammatory CD4 Memory Subset Associated With Relapse in JIA

Researchers demonstrated the role of an inflammatory subset of CD4 memory cells in patients with juvenile idiopathic arthritis who are in remission and will relapse on anti-TNF withdrawal.

An inflammatory CD4 memory subset may be present in patients with juvenile idiopathic arthritis (JIA) before relapse and could discriminate clinical fate before the withdrawal of therapy, according to a study results published in the Annals of the Rheumatic Diseases.

Researchers examined the circulatory immunome of patients with JIA to determine the immunologic differences at the core of the dichotomic clinical fates, using high-dimensional single-cell resolution capabilities of cytometry by time of flight. Samples of peripheral blood mononuclear cells from a well-defined clinical cohort of patients with JIA (n=20) were used to attempt to uncover the CD4 T cell subsets responsible for disease persistence. Patients treated with antitumor necrosis factor alpha (TNFα) biologics with an inactive disease state for at least 6 months were enrolled in the study and subsequently withdrawn from therapy. These patients were rigorously scored for their disease activity by monthly clinical visits for 8 months. Clinical outcome was defined as relapse or remission. A separate JIA cohort (n=16) was used to verify the dysregulation of these circulatory subsets after 8 months.

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Results of the study indicated that an inflammatory memory subset of CD3⁺CD4⁺CD45RA¯TNFα⁺ T cells deficient in immune checkpoints (PD1¯CD152¯) was present in patients who relapsed, before therapy withdrawal. There was a stronger positive correlation of CD45RA¯TNFα⁺ with CD45RA¯CD152¯PD1¯ (r =0.8257) than with CD45RA¯CD152⁺PD1⁺ cells across all subsets of patients (r =0.5987).

The percentage of TNFα⁺ cells was significantly higher in CD45RA¯CD152¯/PD1¯ cells (P <.0001). Although there was perceptible increase in T effectors in the absence of CD152/PD1 in patients with relapse, there was a marked drop to upregulate CD152/PD1, compared with patients in remission.

“By applying a combination of high-dimensionality technologies, we have identified functional perturbations of the immunome in patients with arthritis who will relapse on withdrawal [of] anti-TNFα therapy,” the researchers concluded. “These aberrations show that relapse of clinical disease relies on a foundation of complex and diverse interlacing immune mechanisms, which affect both the effector and regulatory arms of adaptive T cell immunity. Our findings have an immediate translational valency.”


Leong JY, Chen P, Yeo JG, et al. Immunome perturbation is present in patients with juvenile idiopathic arthritis who are in remission and will relapse upon anti-TNFα withdrawal. [published online September 20, 2019]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-216059