Identification and functional analysis of ferritin 2 from the Taiga tick Ixodes persulcatus Schulze

Ferritin 2 (FER2) is an iron storage protein, which has been shown to be critical for iron homeostasis during blood feeding and reproduction in ticks and is therefore suitable as a component for anti-tick vaccines. In this study, we identified the FER2 of Ixodes persulcatus, a major vector for zoonotic diseases such as Lyme borreliosis and tick-borne relapsing fever in Japan, and investigated its functions. Ixodes persulcatus-derived ferritin 2 (Ip-FER2) showed concentration-dependent iron-binding ability and high amino acid conservation, consistent with FER2s of other tick species. Vaccines containing the recombinant Ip-FER2 elicited a significant reduction of the engorgement weight of adult I. persulcatus. Interestingly, the reduction of engorgement weight was also observed in Ixodes ovatus, a sympatric species of I. persulcatus. In silico analyses of FER2 sequences of I. persulcatus and other ticks showed a greater similarity with I. scapularis and I. ricinus and lesser similarity with Hyalomma anatolicum, Haemaphysalis longicornis, Rhipicephalus microplus, and R. appendiculatus. Moreover, it was observed that the tick FER2 sequences possess conserved regions within the primary structures, and in silico epitope mapping analysis revealed that antigenic regions were also conserved, particularly among Ixodes spp ticks. In conclusion, the data support further protective tick vaccination applications using the Ip-FER2 antigens identified herein.     

血液学指标在评估视神经脊髓炎谱系病患者疾病严重程度和治疗效果中的价值

目的 观察常见血液学指标在评估视神经脊髓炎谱系病(NMOSD)疾病严重程度和激素治疗效果中的价值.方法 纳入2015年8月至2020年4月安徽医科大学第一附属医院收治的101例初诊NMOSD患者,治疗前收集患者的一般资料及血液学指标[包括白细胞(WBC)、红细胞(RBC)、血红蛋白(HB)、血小板(PLT)、红细胞分布宽度(RDW)和全血细胞计数衍生参数如中性粒细胞淋巴细胞比率(NLR)、血小板淋巴细胞比率(PLR)、单核细胞淋巴细胞比率(MLR)、嗜酸性粒细胞淋巴细胞比率(ELR)、单核细胞高密度脂蛋白比率(MHR),以及C反应蛋白(CRP)、铁蛋白(FER)、肌酐(CR)、尿酸(UA)、总胆红素(TB)等指标],分别在患者治疗前后行扩展残疾状态量表(EDSS)评分,依据EDSS评分将NMOSD患者病情严重程度分为轻、中、重3组,比较3组间一般资料及血液学指标的差异.结果 3组患者年龄、性别、RBC、HB、RDW、PLT、PLR、ELR、MHR、TB、CR、UA等指标差异无统计学意义(P>0.05);3组间WBC、NLR、MLR、CRP、FER水平比较,差异有统计学意义(P<0.05).有序logistic回归分析结果表明,NLR(OR:1.566,95％CI:1.202～2.039,P<0.05)、FER(OR:1.003,95％CI:1.000～1.005,P<0.05)是NMOSD患者疾病严重程度的独立危险因素.Spearman相关分析结果显示,治疗前EDSS评分与WBC、NLR、MLR、CRP、FER成正相关(r=0.238、0.454、0.339、0.301、0.362,P<0.05);病情变化ΔEDSS(ΔEDSS=治疗前EDSS-治疗后EDSS)与CR成正相关(r=0.420,P<0.05),与MLR呈负相关(r=-0.199,P<0.05).结论 NMOSD患者血液学指标NLR、FER有助于判断疾病严重程度,CR、MLR与激素治疗效果相关.     

Relation between iron content of serum ferritin and clinical status factors extracted by factor analysis in patients with hyperferritinemia

OBJECTIVES: The aims of this study were to develop a new technique for determination of iron content of serum ferritin (ICF, micromol Fe/mg protein) and to investigate relations between ICF and clinical status in patients with hyperferritinemia. METHODS: ICF values were determined by a combination of immunoprecipitation of ferritin and direct colorimetric iron assay. One hundred fifty patients with hyperferritinemia were screened. Factor analysis of the results of 11 laboratory tests was applied to extract factors representing the clinical status of patients. Relations between the extracted factors and the ICF values or serum ferritin concentrations were assessed. RESULTS: Within-run coefficients of variation (CVs) of the ICF assay were <==5.7%. The mean ICF value of 150 patients was 0.423 micromol/mg (SD, 0.211 micromol/mg). Three factors representing clinical status were identified: inflammation, tissue cell damage, and body iron status. Serum ferritin level correlated with all three factors. In contrast, ICF correlated significantly only with the factor representing tissue cell damage (r = 0.293, p = 0.001), and this correlation was independent of inflammation and iron status (p = 0.008). CONCLUSIONS: ICF changes in response to tissue cell damage independent of inflammatory and body iron statuses, whereas serum ferritin changes in response to all three pathologic statuses.     

Hepcidin-to-ferritin ratio: A potential novel index to predict iron overload-liver fibrosis in ß-thalassemia major

ObjectivesWe aimed to determine a threshold cutoff for hepcidin, ferritin, and the hepcidin-to-ferritin ratio in the diagnosis of liver fibrosis caused by iron overload in chronic hepatitis C virus (HCV)-free ß-thalassemia major patients .MethodsThis 1:1-matched case-control study included 102 individuals (3–30 yr.); 51 ß-thalassemia major patients with iron overload , and 51 apparently healthy individuals.ResultsThe highest areas under the receiver operating characteristic curves (AUC-ROCs) for the diagnosis of patients vs. controls had overlapping 95% confidence intervals (CIs): serum hepcidin (0.758; 0.64–0.87;    P ? 0.001), serum ferritin (1.000; 1.00–1.00; P  ?0.001), and the hepcidin/ferritin ratio (1.000; 1.00–1.00; P ? 0.001). For differentiation of patients with liver fibrosis stages of F0–F1 vs. F2–F4 and F0–F1 vs. F3–F4, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) with P-values ? 0.001 were the only statistically significant parameters, while the AUC-ROCs of the hepcidin/ferritin ratio (0.631, P = 0.188 and 0.684, P = 0.098) exhibited 90% and 89.5% sensitivity, respectively, in staging liver fibrosis.ConclusionOur results showed that the hepcidin/ferritin ratio is as effective as the APRI and maybe a better predictor for the diagnosis of liver fibrosis and discriminating its stages, with excellent sensitivity and specificity compared to its components.     

Acute liver failure caused by drug-induced hypersensitivity syndrome associated with hyperferritinemia

Drug-induced hypersensitivity syndrome(DIHS) is a severe reaction usually characterized by fever,rash,and multiorgan failure,occurring 2-6 wk after drug introduction.It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release.A 54-year-old woman was diagnosed with rheumatic arthritis and initiated salazosulfapyridine by mouth.About 10 d later,she had a high fever,skin rash and liver dysfunction.She was admitted to hospital and diagnosed with a drug eruption.She wa...     

Biochemical Markers of Bone Metabolism in Children with <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection

We investigated the biochemical markers of bone metabolism in children with Helicobacter pylori infection. Biochemical markers of bone metabolism and serum levels of vitamin B12, ferritin and estradiol were measured in 41 H. pylori-positive (+) children (23 girls, 18 boys; aged 11.8+/-3 years). Serum levels of intact parathyroid hormone, ss-collagen I carboxy terminal telopeptide, total alkaline phosphatase (ALP), bone-specific ALP, N-terminal cross-links of human procollagen type I, N-mid-osteocalcin, calcium, phosphate, ferritin, and estradiol did not differ significantly between H. pylori(+) and H. pylori negative (-) children. Vitamin B12 levels were significantly decreased in H. pylori(+) compared to H. pylori(-) children. H. pylori infection was not accompanied by significant changes in markers of bone metabolism in children, although vitamin B12 levels were decreased. Further studies are required to clarify whether H. pylori infection causes time-dependent changes in bone turnover markers during the long course of this inflammatory disease.     

血红素加氧酶-1在铁代谢中的作用

铁是机体必需的微量元素,有着广泛的生物学作用,包括氧化运输和细胞呼吸作用,缺铁会引起细胞生长停滞或死亡,铁过载会使细胞发生氧化应激进而损伤细胞膜、蛋白质、核酸.血红素加氧酶-1(HO-1)分解血红素产生铁是铁重复利用最主要的来源,在铁代谢中的作用至关重要.