Amniotic immune biomarkers as risk factors in women with different symptoms of threatened late miscarriage.

PROBLEM: To investigate risk factors that can help identify the possibility of pregnancy loss in threatened late miscarriage (TLM) patients with and without spontaneous uterine contractions. METHOD OF STUDY: Amniotic immune biomarkers (IL2ß receptor, IL6, IL8, IL10, IL1ß, and TNFα) were assayed, and "sludge" was assessed. Patients without intrauterine infections were treated and followed up until delivery, and pregnancy outcomes were recorded. The two groups were compared for the differences in biomarker levels and "sludge," and the independent associations of biomarkers, "sludge," and other maternal factors with late miscarriage were investigated. RESULTS: The amniotic levels of IL2ßR, IL8, and TNFα were higher in the group with contractions (P < .05). When considered alone, each of the six biomarkers was significantly associated with late miscarriage in the no-contractions group and four of these (IL8, IL10, IL1ß, and TNFα) in the contractions group (P < .05). Biomarker levels were correlated, and in multivariate Cox regression analysis, there was an independent effect only for IL8 in the no-contractions group (HR = 18.16, 95% CI: 5.75-57.43) and TNFα in the contractions group (HR = 4.11, 95% CI: 1.68-10.08). For patients with contractions, IL10, IL8, and IL1ß were different in those with and without "sludge," but no such difference was seen in the no-contractions group. CONCLUSION: For TLM patients without intrauterine infections, amniotic immune biomarkers differ between patients with different symptoms, not only for their levels but also for the impact of these biomarkers on the risk of late miscarriage. These findings suggest that the symptoms of TLM should be considered in the study of miscarriage risk.

The imbalance between regulatory memory B cells reveals possible pathogenesis involvement in pediatric immune thrombocytopenia.

Introduction: CD19+CD24hiCD38hi regulatory B cells (Bregs) and CD19+CD27+ memory B cells (Bmems) are B cell subsets with specific immunoregulatory properties. In this study, the balance of these subsets was investigated in pediatric immune thrombocytopenia (ITP) patients, and the frequencies of Bregs and Bmems before and after first-line therapy were measured. Methods: Forty-nine pediatric ITP patients and 19 normal controls were enrolled in this study. The total CD19+ B cells, Bregs and Bmems in the peripheral blood (PB) of all cases were measured by flow cytometry. Results: We found higher frequencies of total CD19+ B cells and Bmems in newly diagnosed ITP patients than those in normal controls (p < 0.01), whereas the frequencies of CD19+CD24hiCD38hi Bregs was significantly lower in ITP patients (p < 0.001). After therapy with MP + IVIG, the level of CD19+CD24hiCD38hi Bregs and Bmems were almost normalized. Conclusion: Our results indicated that pediatric ITP patients were characterized by a decline in CD19+CD24hiCD38hi Bregs and increment of CD19+CD27+Bmems, and an increase of total CD19+ B cells in their peripheral blood.

Regulatory T cells and CD20+ B cells in pediatric very severe aplastic anemia: possible clinical markers for evaluating the therapeutic efficacy and prognosis.

OBJECTIVES: To investigate the immune status of children with very severe aplastic anemia (VSAA), and evaluate the frequencies of CD20+ B cells and Regulatory T cells (Tregs) as potential markers for evaluating the therapeutic efficacy and prognosis. METHODS: We systematically analyzed CD20+ B cells and Tregs using Flow Cytometry in 36 children with VSAA (14 newly diagnosed cases and 22 cases in remission after therapy with HDIVIG + r-ATG + CSA). RESULTS: In newly diagnosed VSAA patients, the percentage of CD20+ B cells was higher than that in healthy children (P < .01), whereas the percentage of Tregs was lower than that in healthy children (P < .001). After treatment with HDIVIG + r-ATG + CSA, the percentage of CD20+ B cells in peripheral blood was decreased obviously, and the percentage of Tregs was significantly increased. CONCLUSION: There is a moderate negative correlation between the percentage of Tregs and CD20+ B cells in our study. Our results shed light on the roles of Tregs and CD20+ B cells as therapeutic efficacy and prognostic markers of pediatric VSAA. Moreover, the mechanism underlying the decrease of blood Tregs and increase of CD20+ B cells in pediatric VSAA patients have been discussed, indicating that Tregs may suppress B cell responses.

Declined Natural Killer Cells Emerging in Women with Unexplained Recurrent Spontaneous Abortion and Further Reducing after Medical Therapy.

BACKGROUND: As focus grows on reproduction, the issue of Recurrent Spontaneous Abortion (RSA), especially for unexplained reasons (URSA), is grabbing more and more attention in gynecological immunology. We investigated the changes of peripheral lymphocyte subsets focusing on whether they had some relationship with development of URSA. METHODS: The percentage and absolute count of lymphocyte subsets (T cells, Th cells, Ts cells, B cells, NK cells) were simultaneously evaluated by flow cytometry in URSA patients (n = 48) and healthy controls (HC, n = 22). RESULTS: Significantly lower percentage and absolute counts of NKT cells and NK cells were observed in URSA compared to the HC. After medical therapy, an obviously increase was shown in the percentage of both T cells and B cells, whereas it presented a reduction in the percentage of NK cells. CONCLUSIONS: The flow cytometry test in T, B, NK cells is a method available to identify URSA patients from healthy women and to provide reference guides for clinical therapy.

Thrombophilia Markers in Patients with Recurrent Early Miscarriage.

BACKGROUND: This study was to investigate the association between thrombophilia and REM by the change of thrombophilia markers and to evaluate their contribution in diagnosis and treatment of REM. METHODS: 199 women with REM history were divided into two groups within the study group: 151 pregnant (REM-P) and 48 nonpregnant (REM-NP). In addition, 121 healthy age-matched women without REM history were divided into two groups of the control group: 75 pregnant (Control-P) and 46 nonpregnant (Control-NP). Lupus anticoagulant (LA), anticardiolipin antibodies (ACA), and anti-ß2-glycoprotein-I antibodies (anti-ß2GPI-ab) and coagulation-related factors such as protein S (PS), protein C (PC), anti-thrombin III (AT-III), and D-dimer were analysed. The prevalence of antiphospholipid antibodies (aPL) and the coagulation-related factors between groups were compared. RESULTS: The overall prevalence of aPL positivity in REM-P (14.57%) showed a difference compared with REM-NP (2.66%) but not for aCL, anti-ß2GPI-ab or LA alone. There were significant differences in the mean levels of protein S, protein C, and AT-III in REM-P. The mean values of protein C (90.3 ± 28.42%) and protein S (71.80 ± 24.68%) in the aPL positive study group were similar with that of the aPL negative study group (p = 0.406, p = 0.880). Comparing with the aPL negative study group, the mean value of AT-III (87.71 ± 21.84%) was significantly lower (p = 0.018), while the mean value of D-dimer (0.98 ± 1.1 mg/L FEU) was significantly higher (p = 0.013). CONCLUSIONS: We briefly address the role of the prevalence of aPL and the related coagulation factors for predicting a prethrombotic state in patients with REM. The results of the use of anticoagulants for treating REM are encouraging.