Combination of pegylated interferon-alpha and nucleos(t)ide analogue treatment enhances the activity of natural killer cells in nucleos(t)ide analogue experienced chronic hepatitis B patients
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Authors: Pang, X.; Zhang, L.; Liu, N.; Liu, B.; Chen, Z.; Li, H.; Chen, M.; Peng, M.; Ren, H.; Hu, P.
Abstract
A combination of pegylated interferon-alpha (peg-IFN-alpha) and nucleos(t)ides analogue (NA) therapy can effectively reduce hepatitis B surface antigen (HBsAg), especially in NA-experienced chronic hepatitis B (CHB) patients. However, the immune mechanism of this therapy is unclear. Forty NA-experienced CHB patients were enrolled into this study. The frequencies of peripheral blood natural killer (NK) cells, dendritic cells (DCs), CD4(+)T cells, CD8(+)T cells, T helper (Th) cells, regulatory T cells (T-reg), B cells and follicular T helper (Tfh) cells were evaluated by flow cytometry. Seven of the 40 patients converted to peg-IFN-alpha combined with NA treatment, while the other 33 continued to NA therapy. The decrease in HBsAg was more pronounced in the combination treatment group, and only patients receiving combination treatment achieved HBsAg loss. The frequency and absolute number of CD56(bright)NK cells in the combination treatment group increased significantly compared with the NA treatment group, whereas the CD56(dim)NK cells were decreased. In the NA treatment group, the proportions of CD4(+)T(N), CD8(+)T(N), CD19(+)B and cytotoxic T lymphocyte antigen-4 (CTLA-4)(+)CD4(+)T cells were increased, while the proportions of CD4(+)T(EM), CD8(+)T(EM), CD25(+)CD4(+)T(reg), CD25(high)CD4(+)T(reg), CD127(low)CD25(+)T(reg), programmed cell death 1 (PD-1)(+)CD4(+)T, PD-1(+)CD8(+)T, CTLA-4(+)CD8(+)T, CCR4(+)CD25(+)T(reg)and CCR4(+)CD25(high)T(reg)cells were decreased after therapy. For NA-experienced CHB patients who achieved low HBsAg levels, combination treatment is more likely to result in HBsAg decline and HBsAg clearance by increasing the activity of CD56(bright)NK cells.
Dendritic cells as predictive markers of responsiveness to hydroxychloroquine treatment in primary cicatricial alopecia patients
DERMATOLOGIC THERAPY
Authors: Klosowicz, Agata; Pastuszczak, Maciej; Dyduch, Grzegorz; Englert, Karolina; Lukasik, Adriana; Wojas-Pelc, Anna
Abstract
Primary cicatricial alopecia (PCA) encompasses a diverse group of inflammatory diseases characterized by the irreversible replacement of hair follicle structures by fibrous tissue. Although the pathogenesis of PCA remains not fully understood, the key to its understanding might be the location of dendritic cells (DCs) inflammatory infiltrate. One of the systemic therapy of choice in PCA patients is hydroxychloroquine (HCQ). We hypothesized that DCs are implicated in PCA pathogenesis and that they might constitute the biological target of HCQ treatment. For these reasons, we investigated whether DCs could affect the antimalarial responsiveness, and if DCs might be used as predictive factor of responsiveness to HCQ. In this retrospective cohort study, 65 patients diagnosed with PCA were grouped accordingly to their response to HCQ therapy. Skin biopsies had been taken before the treatment was started. Cell count was performed on immunohistochemistry by using characteristic monoclonal antibodies to specific subpopulations of DCs. In almost every second patient (47.7%), we observed remission of the disease during HCQ treatment. The number of plasmacytoid and myeloid DCs as well as Langerhans cells in lesional skin of HCQ responders was higher in comparison with HCQ nonresponders. Moreover, in a predictive model receiver operating characteristic (ROC curve) we showed that plasmacytoid DCs might be used as a predictive factor of responsiveness to HCQ. The results of this study are important as identifying biomarkers for responsiveness to a HCQ therapy will be helpful to individualize treatment and make it more effective.