Th type 17 (Th17) cells have been identified as a proinflammatory T‐cell subset. Here, we investigated the regulation of human Th17 cells by fetal BM‐derived mesenchymal stem cells (FBM‐MSC). We cocultured FBM‐MSC with human PBMC or CD4⁺ T cells from healthy donors. FBM‐MSC significantly suppressed the proliferation of CD4⁺ T cells stimulated by PHA and recombinant IL‐2. Significantly higher levels of IL‐17 were observed in FBM‐MSC cocultured with either PBMC or CD4⁺ T cells than that in PBMC cultured alone or CD4⁺ T cells cultured alone. Flow cytometry analysis showed that the percentage of Th17 cells in coculture of FBM‐MSC and CD4⁺ T cells was significantly higher than that in CD4⁺ T‐cell cultured alone. FBM‐MSC did not express IL‐17 protein. Consistent with the augmentation of Th17 cells, significantly higher levels of IL‐6 and IL‐1 were observed in coculture of FBM‐MSC and CD4⁺ T cells than that in CD4⁺ T‐cell culture, while the levels of IL‐23 were similar between FBM‐MSC + PBMC coculture and PBMC alone, or FBM‐MSC + CD4⁺ T‐cell and CD4⁺ T‐cell alone. The presence of FBM‐MSC decreased the percentage of Th1 cells, but minimally affected the expansion of CD4⁺CD25⁺ T cells. In conclusion, our data demonstrate for the first time that FBM‐MSC promote the expansion of Th17 cells and decrease IFN‐γ‐producing Th1 cells. These data suggest that IL‐6 and IL‐1, instead of IL‐23, may be partly involved in the expansion of Th17 cells.

BAFF (B-cell activating factor belonging to the TNF family) is an essential component of B-cell homeostasis, and is required for the normal survival and development of B cells. To further explore the role of this cytokine in the pathogenesis of idiopathic thrombocytopenic purpura (ITP), BAFF/BAFF-R (one of receptors of BAFF) expression levels were determined and the correlation between the clinical parameters and the BAFF expression levels was analyzed. A total of 57 patients with ITP were enrolled and 25 age and sex-matched healthy volunteers served as controls. Serum was obtained from 41 patients with ITP and 22 healthy volunteers and was analyzed with a commercial human soluble BAFF (sBAFF) ELISA kit. BAFF and BAFF-R mRNA expression of peripheral blood (PB) (n = 42) and splenocytes (SP) (n = 8) mononuclear cells (MNC) were determined by real-time quantitative PCR. The SPMNC of normal controls came from three hereditary spherocytosis patients who underwent splenectomy. The untreated patients with ITP had higher serum BAFF levels (Median 1430 pg/ml, Range: 534–5787 pg/ml) than those of normal controls (Median 1120 pg/ml, Range: 640–2376 pg/ml, p = 0.006) and treated ITP group (Median 662 pg/ml, Range 267–1265 pg/ml, p = 0.000). On the other hand, serum BAFF levels of treated patients with ITP were lower than those of normal controls (p = 0.001). There was a weak correlation (the Pearson correlation coefficient is − 0.242) between platelet count and BAFF (p = 0.064). However, BAFF levels did not correlate with platelet associated immunoglobulin or immunoglobulin levels. Moreover, the serum BAFF levels were not statistically different between acute and chronic ITP (p = 0.841). PBMNC of ITP had higher BAFF but not BAFF-R mRNA expression than that of normal controls. BAFF mRNA expression of SPMNC had a positive correlation with BAFF-R in ITP patients but not in PBMNC of normal controls and untreated ITP patients. The BAFF-R mRNA expression of SPMNC was shown to be 15.29 times higher than that of PBMNC in ITP. BAFF might contribute to autoimmunity and disease development in ITP. However, BAFF serum level must be carefully considered as a surrogate marker of disease activity in ITP.

Background: As a new non-factor therapy for hemophilia A (HA), real-world study of emicizumab is still scarce. This study aimed to investigate the real-world use of emicizumab in Chinese boys with HA.Methods: Patients with moderate or severe HA were enrolled at Beijing Children's Hospital. They take emicizumab weekly (3 mg/kg) for a month and then went into a maintenance period with a different dosing regimen. After obtaining platelet-poor plasma at end of the loading period and during the maintenance period, coagulation ability and FVIII inhibitor were determined using human and bovine chromogenic Bethesda assay. Patients' bleeding rates were calculated through patients' records from 24 weeks before to at least 6 months after the switch (to emicizumab).Result: In total, 13 pediatric patients with HA (severe: moderate = 11:2) were enrolled in this study. The patients' age was 3.51 (0.73–6.65) years. Eight had FVIII inhibitors at enrollment and one of them developed FVIII inhibitors again during the switch. The coagulation level of the maintenance period was 19.6 (13.5–32.8) IU/dL (N = 10). The median dose of each emicizumab injection was 2.7 (1.3–3.8) mg/kg and the monthly consumption of emicizumab was 5.2 (3.2–6.8) mg/kg/month. After switching to emicizumab, reduced annualized bleeding rate (ABR) [0.5 (0–4) vs. 4 (0–18), P < 0.01], annualized joint bleeding rate (AJBR) [0 (0–1.1) vs. 1.0 (0–12), P < 0.01], and annualized spontaneous bleeding rate (ASBR) [0 (0–1) vs. 2.0 (0–18), P < 0.01] were observed. In patients with or without FVIII inhibitor, similar ABR [0.33 (0–4) vs. 0.5 (0–3), P = 0.78], AJBR [0 (0–1.1) vs. 0 (0–0.5), P = 0.63], and ASBR [0 (0–1) vs. 0 (0–1.5), P = 0.73] were also noticed. Five inhibitor-positive patients (at enrollment) all had their inhibitor titer reduced. In addition, all target joints vanished after switching to emicizumab.Conclusion: Emicizumab could reduce bleeds in pediatric patients with/without FVIII inhibitors and eliminate target joints.