Activin a suppresses peripheral CD8+ T lymphocyte activity in acute-phase Kawasaki disease

Abstract

Background Kawasaki disease is an autoimmune disease characterized by systemic vasculitis of unknown aetiology and most commonly occurs in children under 5 years old. Previous studies have found that the over-activation of lymphocytes is an important mechanism of Kawasaki disease. Activin A, also known as immunosuppressive factor P, is a multifunctional growth and transforming factor. However, whether activin A is involved in the regulation of peripheral lymphocytes activity in Kawasaki disease is unclear. Thus, we aimed to investigate the effect of activin A on the activity of peripheral lymphocytes in acute-phase Kawasaki disease. Methods Seven patients with Kawasaki disease and seven healthy controls were studied. Peripheral blood lymphocytes were isolated by Ficoll density gradient centrifugation. The activation of CD4+ and CD8+ T cells and CD19+ B cells was investigated by flow cytometry. The expression of activin type IIA receptors was investigated by flow cytometry. Results Immune imbalance in CD4 and CD8 lymphocytes were detected in acute-phase Kawasaki disease. The expression of activin type IIA receptors on CD8+ T cells and CD19+ B cells was increased in acute-phase Kawasaki disease and decreased following treatment with activin A. Activin A suppressed the expression of CD25 and CD69 on CD8+ T cells and the expression of CD69 on CD19+ B cells. Conclusions The expression of activin type IIA receptor was increased on CD8+ T cells and CD19+ B cells in Kawasaki disease. Activin A suppressed the expression of CD25, CD69 and activin type IIA receptors on peripheral CD8+ T lymphocyte. Activin A plays different roles in different lymphocyte subsets and suppresses peripheral CD8+ T lymphocyte activity in acute-phase Kawasaki disease.

Immunophenotyping of peripheral blood cells allows to discriminate MIS-C and Kawasaki disease

“…These data is in agreement with a previous study that described a significant T lymphopenia (in our case we found also a significant reduction of B lymphocytes) during the acute phase of MIS-C with the subsequent reversion during resolution, again similarly to what we observed in adult patients with severe COVID, that had a significant B and T cell lymphopenia [ 12 ] reverted after one week of hospitalization [ 13 ]. While, differently from our results, a previous study described the alteration of cytotoxic lymphocytes in KD [ 16 ] and another reported a suppression of peripheral activity but not a reduction of the number of CD8 in 7 patients with KD [ 14 ].…”

“…The deep immune profiling of patients with MIS-C demonstrated a marked, although transient, lymphopenia with a more pronounced T-cell involvement i.e., the same profile that we observed in adult patients with severe, acute Sars-CoV-2 infection [ 12 , 13 ]. Furthermore, a suppression of CD8 was reported in KD [ 14 ]. The circulating cell profile of patients with the two diseases helps to define diagnostic biomarkers that may contribute to the early diagnosis of each of the two entities and also to discriminate between them [ 15 ] since different outcome and therapy response were reported in patients with KD and MIS-C [ 16 ].…”

Different Immunoregulation Roles of Activin A Compared With TGF-β

“…Similar to TGF-β blockade, knockdown (KD) of activin A induced CD8 + T cells priming during radiation therapy of 4T1 tumor-bearing mice, and combination of TGF-β blockade with acitivin A KD significantly augmented this effect ( 55 , 56 ). Activin A could also inhibit the activity of CD8 + T cells in peripheral blood of acute Kawasaki disease patients ( 57 ).…”