Patients with treated autoimmune hepatitis and persistent suppression of plasmacytoid dendritic cells: A different point of view

Abstract

Objectives: Plasmacytoid dendritic cells (pDCs) have been shown to have a role in autoimmune diseases, but their role in Autoimmune Hepatitis (AIH) is not completely clear. In the present study, we assessed the frequency of pDCs in peripheral blood of AIH patients under long-term standard immunosuppressive therapy. Methods: This cross-sectional analysis enrolled 27 AIH patients and 27 healthy controls. We analyzed and compared their proportion of pDCs, CD4⁺, CD8⁺, γδ T cells, CD25⁺ regulatory T (Treg) cells, FoxP3⁺, Foxp3⁺CD39⁺ Treg cells, total B (CD19⁺) cells, and plasma cells (CD38⁺) in peripheral blood using flow cytometry immunophenotyping. Results: AIH patients had a lower percentage of pDCs (median frequencies of 0.2% vs. 0.4%; p = .002) and higher expression of CD8 T cells (32.5% vs 28.6%; p = 0.008) in peripheral blood, when compared to healthy controls. We did not find statistically significant differences between the groups regarding the other cell subtypes.Conclusion: Our data suggest a persistent suppression of pDCs in AIH patients, along with increased CD8 T cell activity, years after AIH diagnosis and despite of good clinical response to treatment, thus pointing to a role of pDCs in the AIH pathogenesis.

Keywords: autoimmune hepatitis; flow cytometry; plasmacytoid dendritic cells.

Figure 1.

Flow cytometry plots showing the median rate of pDC in (a) patients with AIH under immunosuppressant therapy and (b) healthy controls, and comparison between both groups in a dot plot graphic (c). Flow cytometry plot showing the median CD8⁺ T cells in (d) patients with AIH under immunosuppressant therapy and (e) healthy controls, and comparison between both groups in a dot plot graphic (f). The middle bar in the dot plots indicates the median, the lower and upper bars indicate the first and third quartiles, respectively. AIH: Autoimmune Hepatitis

Figure 2.

Dot plot graphics showing the (a) rate of T (CD3⁺) cells, (b) rate of helper (CD4⁺) T cells between all T cells, (c) ratio between CD4⁺ and CD8⁺ T cells within T cells, (d) rate of γδ T cells within T cells, (e) rate of regulatory T (Treg) cells expressing (CD25⁺) within T cells, (f) rate of Treg cells expressing FoxP3 (CD3⁺CD4⁺FoxP3⁺) within T cells, (g) rate of Treg cells expressing FoxP3 and CD39 (CD3⁺CD4⁺FoxP3⁺CD39⁺), (h) rate of B (CD19⁺) cells, and (i) rate of plasma cells (CD19⁺CD38⁺) within B cells. The middle bars indicate the medians; the lower and upper bars indicate the first and third quartiles, respectively. (ns) not significant; *p ≤ 0.05.