Key result
In children with Kawasaki disease, the percentages of activated circulating follicular helper T cell subsets and serum IL-21 levels were significantly increased during the acute phase compared to healthy controls.
Why the study?
Although cTfh cells are associated with disease progression and severity in multiple conditions, their role in the development of Kawasaki disease had not been investigated.
Case-Control (n=44)
Yes
Circulating follicular helper T cells and serum IL-21 levels are significantly elevated in the acute phase of Kawasaki disease, suggesting their essential role in its immune pathogenesis.
Supports Tfh/IL-21 investigation in Kawasaki disease; hypothesis-generating and should not change practice.
Circulating follicular helper T (cTfh) cells are a specialized subset of CD4 + T cells that express the CXC-chemokine receptor 5 (CXCR5). These cells exhibit immune activities by inducing B cell differentiation and proliferation via the secretion of interleukin (IL)-21. Multiple studies have demonstrated that cTfh cells are associated with the progression and severity of numerous diseases. To investigate the role of cTfh cells in the development of Kawasaki disease (KD), we analyzed the distinct subpopulations of cTfh cells and serum IL-21 levels in different phases of KD. According to the differential expression of inducible co-stimulator (ICOS) and programmed cell death protein 1 (PD-1), cTfh cells were divided into distinct subsets. We used flow cytometry and flow cytometric bead arrays (CBA) to analyze subsets of CD4 + CXCR5 + T cells and serum IL-21 levels. The samples were collected from control subjects and Kawasaki disease patients in the acute and remission phases. In the acute phase (AP), the percentages of ICOS high PD-1 high , ICOS + PD-1 + , ICOS − PD-1 + , CD45RA − IL-21 + cTfh cells and serum IL-21 levels significantly increased. Furthermore, the percentages of ICOS high PD-1 high and ICOS + PD-1 + cTfh cells positively correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values, whereas the percentage of ICOS − PD-1 + cTfh cells indicated negative correlations. The percentages of ICOS + PD-1 + , ICOS high PD-1 high and CD45RA − IL-21 + cTfh cells correlated positively with serum IL-21 levels. In the remission phase (RP), the percentages of ICOS − PD-1 + , CD45RA − IL-21 + cTfh cells and serum IL-21 levels were significantly decreased. In contrast, the percentages of ICOS + PD-1 + , ICOS high PD-1 high , and ICOS + PD-1 − cTfh cells were further increased. Among these subsets, only CD45RA − IL-21 + cTfh cells correlated positively with serum IL-21 levels. The present study is the first investigation that examined the distribution of circulating cTfh cell subsets in Kawasaki disease. Both cTfh cells and serum IL-21 are essential to the pathogenesis of KD. Our study provides further understanding of the immune response involved in KD and offers novel insights in the pathogenetic mechanism of this disease.
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Xu et al. (2018) conducted a case-control in Kawasaki disease (n=44). Kawasaki disease vs. Healthy age-matched controls was evaluated on Percentages of circulating Tfh cell subsets and serum IL-21 levels. In children with Kawasaki disease, the percentages of activated circulating follicular helper T cell subsets and serum IL-21 levels were significantly increased during the acute phase compared to healthy controls.
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