[Expression and Clinical Significance of Serum sFas/sFasL in Patients with Secondary Hemophagocytic Lymphohistiocytosis].

OBJECTIVE: To investigate the expression and clinical significance of soluble Fas (sFas) and sFasL in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). METHODS: From September 2015 to December 2020, 86 sHLH patients who met the HLH2004 diagnostic criteria were collected. They were divided into 55 cases in the MAHLH group and 31 cases in the NonMAHLH group according to the etiology. Thirty healthy persons were chosen as the normal control group, and 20 patients with systemic lupus erythematosus (SLE) were chosen as the disease control group. The expression levels of sFas and sFasL in the serum of patients with each group were detected by ELISA, and the clinical data were collected for statistical analysis. The significance of sFas and sFasL in sHLH was analyzed by ROC curve. RESULTS: Serum levels of sFas and sFasL in patients with newly diagnosed sHLH were significantly higher than those in disease control group and normal control group (P<0.01). The levels of sFas and sFasL in MAHLH group were significantly higher than those in nonMAHLH (infection related HLH and autoimmune disease related HLH) group (P<0.01). The serum levels of sFas and sFasL in 17 newly treated patients with sHLH (17/86) after treatment were significantly lower than those before treatment (P<0.01). The serum sFas level in newly diagnosed sHLH patients was positively correlated with SF(r=0.35), sCD25(r=0.79) and sFasL(r=0.73). The serum sFasL level was positively correlated with SF(r=0.39), sCD25(r=0.64) and sFas(r=0.73). Compared with the NonMAHLH group, the area under the ROC curve was 0.707 (95% CI: 0.593-0.821) (P=0.0015). The optimal critical value for diagnosing MAHLH by sFas level was 12 743 pg/ml, and the sensitivity and specificity were 70.9% and 71% respectively. Compared with the NonMAHLH group, the area under the ROC curve was 0.765(95% CI: 0.659-0.87)(P<0.01). The median OS time of sFas high expression group (≥16798.5 pg/ml) and sFasL high expression group (≥4 785 pg/ml) was significantly shorter than that of the low expression group (P<0.001). CONCLUSION: Serum levels of sFas and sFasL can be used for the early diagnosis and differential diagnosis of sHLH disease, and are the factor related to the poor prognosis of sHLH.

Low T3 syndrome is a prognostic marker of poor outcomes in secondary hemophagocytic lymphohistiocytosis.

This study aimed to examine the association between low T3 syndrome and overall survival (OS) in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). The study consisted of 111 consecutive patients hospitalized due to newly diagnosed sHLH with detailed thyroid hormone profiles on admission. Low T3 syndrome was found in 75.7% of the studied sHLH population. After a median follow-up of 83 (interquartile range 25-365) days, there were 60 (71.4%) cumulative deaths in the low T3 syndrome group and 13 (48.1%) in the euthyroid group. Survival analysis showed a lower survival probability for patients with low FT3 than for those with normal FT3 (median OS, 60 vs. 365 days, p = .011). In the multivariate analysis, low T3 syndrome was an independent prognostic factor for OS (HR = 2.474; 95% CI 1.351-4.532, p = .003). Low T3 syndrome is frequently found and associated with worse outcomes in patients with sHLH.

[Expression and Clinical Significance of Soluble B7-H3 in Patient with Secondary Hemophagocytic Lymphohistiocytosis].

OBJECTIVE: To investigate the expression and clinical significance of soluble B7-H3 (sB7-H3) in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). METHODS: The plasma samples of 85 newly diagnosed sHLH patients from December 2012 to April 2018 were collected. The patients were divided into lymphoma-related HLH（LHLH）group and infection-related HLH（IHLH）group. The expression of sB7-H3 in plasma was detected by ELISA, and the clinical data were collected for analysis. Fifteen healthy people were chosen as control group. RESULTS: The expression level of sB7-H3 in lymphoma-related HLH and infection-related HLH group significant increased as compared with the control group, (P＜0.05), and the expression level of sB7-H3 in lymphoma-related HLH group was significant higher than that in infection-related HLH group [(35.75± 9.90) vs (28.70±8.95) ng/ml)] (P＜0.001). There were no significant statistical difference in the expression of some clinical factors (including age, fever, splenomegaly, ANC, Plt, FIB, calcium ion, serum albumin, LDH, serum ferritin, sCD25) in lymphoma-related HLH and infection-related HLH group (P＞0.05). The evaluation of expression and significance of sB7-H3 in sHLH by using ROC curve, showed that the area under ROC curve comparison of patients in lymphoma-related HLH group and infection-related HLH group was 0.718 (95% CI 0.610-0.810) (P=0.0002), and predicting the sensitivity and specificity of the lymphoma-related HLH patients were 77.36% and 59.38%, respectively. The best cut-off value of patients in sB7-H3 was 29.81 ng/ml, the overall survival time of sB7-H3 high-expression group (≥29.81 ng/ml) was significant shorter than that in low-expression group (＜29.81 ng/ml) (24 vs 440 d) (P＜0.001). The clinical factors affecting the survival status of sHLH patients were neutrophils, albumin, serum ferritin, serum calcium ions and sB7-H3 levels. CONCLUSION: sB7-H3 associates with poor prognosis of sHLH patients, and may be involved in disease progression.

Correlation between HCN4 gene polymorphisms and lone atrial fibrillation risk.

Background and objective: Atrial electrical remodelling (AER) was significantly associated with atrial fibrillation (AF) development. Polymorphisms in hyperpolarization activated cyclic nucleotide gated potassium channel 4 (HCN4) gene might be correlated with AER. In the present study, we explored the association of HCN4 polymorphisms (rs498005 and rs7164883) with lone AF risk in a Chinese Han population. Methods: In this case-control study, the Sanger sequencing method was utilized to genotype the HCN4 polymorphisms. Relative risk of AF was assessed by the χ2 test, and presented by odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Logistic regression analysis was performed for multivariate analysis. The effects of HCN4 polymorphisms on AF clinical features were analyzed by the Mann-Whitney U test and adjusted by the Bonferroni method. Results: C allele of rs498005 was significantly correlated with increased risk of AF (OR = 1.412, 95%CI = 1.012-1.970), and the association still exited after adjustment by age, gender, the status of smoking and drinking, histories of diabetes, hyperlipidaemia and myocardial infarction (adjusted OR = 1.473, 95%CI = 1.043-2.081). G allele of rs7164883 SNP was marginally associated with enhanced AF risk after adjustment by the above clinical parameters (adjusted OR = 1.742, 95%CI = 1.019-2.980). Atrial late potential (ALP), including TP (P wave duration after filtering) and LP20 (the amplitude of superimposed potential in the final 20 ms of P wave) were significantly associated with rs498005 genotype (p < .001). Conclusion: HCN4 rs498005 and rs7164883 polymorphisms are significantly associated with AF risk.