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1.
No commercial immunodiagnostic tests for human scabies are currently available, and existing animal tests are not sufficiently sensitive. The recombinant Sarcoptes scabiei apolipoprotein antigen Sar s 14.3 is a promising immunodiagnostic, eliciting high levels of IgE and IgG in infected people. Limited data are available regarding the temporal development of antibodies to Sar s 14.3, an issue of relevance in terms of immunodiagnosis. We utilised a porcine model to prospectively compare specific antibody responses to a primary infestation by ELISA, to Sar s 14.3 and to S. scabiei whole mite antigen extract (WMA). Differences in the antibody profile between antigens were apparent, with Sar s 14.3 responses detected earlier, and declining significantly after peak infestation compared to WMA. Both antigens resulted in >90% diagnostic sensitivity from weeks 8–16 post infestation. These data provide important information on the temporal development of humoral immune responses in scabies and further supports the development of recombinant antigen based immunodiagnostic tests for recent scabies infestations.  相似文献   

2.
The scabies mite, Sarcoptes scabiei var. hominis, infests human skin, causing allergic reactions and facilitating bacterial infection by Streptococcus sp., with serious consequences such as rheumatic fever and rheumatic heart disease. To identify a possible drug target or vaccine candidate protein, we searched for homologues of the group 3 allergen of house dust mites, which we subsequently identified in a cDNA library. The native protein, designated Sar s 3, was shown to be present in the mite gut and excreted in fecal pellets into mite burrows within the upper epidermis. The substrate specificity of proteolytically active recombinant rSar s 3 was elucidated by screening a bacteriophage library. A preference for substrates containing a RS(G/A) sequence at the P1-P2′ positions was revealed. A series of peptides synthesized as internally quenched fluorescent substrates validated the phage display data and high performance liquid chromatography/mass spectrometry analysis of the preferred cleaved substrate and confirmed the predicted cleavage site. Searches of the human proteome using sequence data from the phage display allowed the in silico prediction of putative physiological substrates. Among these were numerous epidermal proteins, with filaggrin being a particularly likely candidate substrate. We showed that recombinant rSar s 3 cleaves human filaggrin in vitro and obtained immunohistological evidence that the filaggrin protein is ingested by the mite. This is the first report elucidating the substrate specificity of Sar s 3 and its potential role in scabies mite biology.  相似文献   

3.

Background

Scabies is a disease of worldwide significance, causing considerable morbidity in both humans and other animals. The scabies mite Sarcoptes scabiei burrows into the skin of its host, obtaining nutrition from host skin and blood. Aspartic proteases mediate a range of diverse and essential physiological functions such as tissue invasion and migration, digestion, moulting and reproduction in a number of parasitic organisms. We investigated whether aspartic proteases may play role in scabies mite digestive processes.

Methodology/Principle Findings

We demonstrated the presence of aspartic protease activity in whole scabies mite extract. We then identified a scabies mite aspartic protease gene sequence and produced recombinant active enzyme. The recombinant scabies mite aspartic protease was capable of digesting human haemoglobin, serum albumin, fibrinogen and fibronectin, but not collagen III or laminin. This is consistent with the location of the scabies mites in the upper epidermis of human skin.

Conclusions/Significance

The development of novel therapeutics for scabies is of increasing importance given the evidence of emerging resistance to current treatments. We have shown that a scabies mite aspartic protease plays a role in the digestion of host skin and serum molecules, raising the possibility that interference with the function of the enzyme may impact on mite survival.  相似文献   

4.

Background

The resident skin microbiota plays an important role in restricting pathogenic bacteria, thereby protecting the host. Scabies mites (Sarcoptes scabiei) are thought to promote bacterial infections by breaching the skin barrier and excreting molecules that inhibit host innate immune responses. Epidemiological studies in humans confirm increased incidence of impetigo, generally caused by Staphylococcus aureus and Streptococcus pyogenes, secondary to the epidermal infestation with the parasitic mite. It is therefore possible that mite infestation could alter the healthy skin microbiota making way for the opportunistic pathogens. A longitudinal study to test this hypothesis in humans is near impossible due to ethical reasons. In a porcine model we generated scabies infestations closely resembling the disease manifestation in humans and investigated the scabies associated changes in the skin microbiota over the course of a mite infestation.

Methodology/Principal Findings

In a 21 week trial, skin scrapings were collected from pigs infected with S. scabies var. suis and scabies-free control animals. A total of 96 skin scrapings were collected before, during infection and after acaricide treatment, and analyzed by bacterial 16S rDNA tag-encoded FLX-titanium amplicon pyrosequencing. We found significant changes in the epidermal microbiota, in particular a dramatic increase in Staphylococcus correlating with the onset of mite infestation in animals challenged with scabies mites. This increase persisted beyond treatment from mite infection and healing of skin. Furthermore, the staphylococci population shifted from the commensal S. hominis on the healthy skin prior to scabies mite challenge to S. chromogenes, which is increasingly recognized as being pathogenic, coinciding with scabies infection in pigs. In contrast, all animals in the scabies-free cohort remained relatively free of Staphylococcus throughout the trial.

Conclusions/Significance

This is the first experimental in vivo evidence supporting previous assumptions that establishment of pathogens follow scabies infection. Our findings provide an explanation for a biologically important aspect of the disease pathogenesis. The methods developed from this pig trial will serve as a guide to analyze human clinical samples. Studies building on this will offer implications for development of novel intervention strategies against the mites and the secondary infections.  相似文献   

5.
BackgroundMultiple recent outbreaks of Rift Valley Fever (RVF) in Africa, Madagascar, and the Arabian Peninsula have resulted in significant morbidity, mortality, and financial loss due to related livestock epizootics. Presentation of human RVF varies from mild febrile illness to meningoencephalitis, hemorrhagic diathesis, and/or ophthalmitis with residual retinal scarring, but the determinants for severe disease are not understood. The aim of the present study was to identify human genes associated with RVF clinical disease in a high-risk population in Northeastern Province, Kenya.Conclusions/SignificanceOf the 46 SNPs tested, TLR3, TLR7, TLR8, MyD88, TRIF, MAVS, and RIG-I were repeatedly associated with severe symptomatology, suggesting that these genes may have a robust association with RVFV-associated clinical outcomes. Studies of these and related genetic polymorphisms are warranted to advance understanding of RVF pathogenesis.  相似文献   

6.
The cellular response in the dermis of common wombats (Vombatus ursinus) with sarcoptic mange exhibited some typical aspects of an immune response to Sarcoptes scabiei. There was an induction phase for wombats experimentally infected with S. scabiei represented by absence of a dermal inflammatory infiltrate for at least 12 days after infection. T lymphocytes, plasma cells, mast cells, and neutrophils then entered the dermis, consistent with a type IV (delayed) hypersensitivity response. In free-living wombats with severe parakeratotic sarcoptic mange eosinophils were also present in the dermis suggesting that a type I (immediate) hypersensitivity response may develop after a type IV hypersensitivity response. Absence of plasma cells and B lymphocytes in free-living wombats with severe parakeratotic sarcoptic mange compared with their presence in wombats experimentally infected with S. scabiei suggested that some immune tolerance may develop with severe infections. A large proportion of cells in the dermal response were not identified but were possibly cells of connective tissue. The thickness of the epidermis increased within 4 days in response to S. scabiei infection. Some antibodies raised against human leucocyte antigens CD3, CD5, HLA-DP, DQ, DR, and CD79b cross-reacted with leucocyte antigens of common wombats and were used to identify cell types in inflammatory infiltrates using immunohistochemistry.  相似文献   

7.
8.
BackgroundScabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative.Conclusions/SignificanceOur data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.  相似文献   

9.
10.
Transarterial chemoembolization (TACE) has therapeutic effects in patients with unresectable hepatocellular carcinoma (HCC), but its impact on the cellular immune response during disease progression is largely unknown. Here we conducted a prospective study to evaluate the effect of TACE on immune status and to identify prognostic immune markers governing treatment success. In this study, 51 stage III HCC patients, 28 stage I HCC patients (TNM classification) and 20 healthy donors were enrolled. Flow cytometry and cytometric bead array were used to evaluate the circulating immune cell subsets, including CD4+ T cells (Th1, Th17 and Treg cells), CD8+ T cells, NK cells, and NKT cells, and plasma cytokines before TACE and 30 days after TACE. Interestingly, among those immune parameters, the frequency of circulating Th17 cells was higher in stage III HCC patients than in stage I HCC patients (P = 0.015) and healthy donors (P<0.001). Moreover, an increased frequency of circulating Th17 cells was observed 30 days after TACE (Th17D30) compared with the baseline level (P = 0.036). Kaplan-Meier analysis demonstrated that Th17D30 was positively associated with overall survival (OS; P = 0.007) and time to progression (TTP; P = 0.009). Multivariate Cox analysis revealed that Th17D30 was an independent prognostic factor for OS (HR = 0.317, P = 0.032) and TTP (HR = 0.304, P = 0.010). These results provide a potential prognostic marker for stage III HCC patients undergoing TACE and may be useful for identifying patients who can benefit from adjuvant immunotherapies.  相似文献   

11.
BackgroundThe suboptimal sensitivity and specificity of available diagnostic methods for scabies hampers clinical management, trials of new therapies and epidemiologic studies. Additionally, parasitologic diagnosis by microscopic examination of skin scrapings requires sample collection with a sharp scalpel blade, causing discomfort to patients and difficulty in children. Polymerase chain reaction (PCR)-based diagnostic assays, combined with non-invasive sampling methods, represent an attractive approach. In this study, we aimed to develop a real-time probe-based PCR test for scabies, test a non-invasive sampling method and evaluate its diagnostic performance in two clinical settings.Methodology/Principal findingsHigh copy-number repetitive DNA elements were identified in draft Sarcoptes scabiei genome sequences and used as assay targets for diagnostic PCR. Two suitable repetitive DNA sequences, a 375 base pair microsatellite (SSR5) and a 606 base pair long tandem repeat (SSR6), were identified. Diagnostic sensitivity and specificity were tested using relevant positive and negative control materials and compared to a published assay targeting the mitochondrial cox1 gene. Both assays were positive at a 1:100 dilution of DNA from a single mite; no amplification was observed in DNA from samples from 19 patients with other skin conditions nor from house dust, sheep or dog mites, head and body lice or from six common skin bacterial and fungal species. Moderate sensitivity of the assays was achieved in a pilot study, detecting 5/7 (71.4% [95% CI: 29.0% - 96.3%]) of clinically diagnosed untreated scabies patients). Greater sensitivity was observed in samples collected by FLOQ swabs compared to skin scrapings.Conclusions/SignificanceThis newly developed qPCR assay, combined with the use of an alternative non-invasive swab sampling technique offers the possibility of enhanced diagnosis of scabies. Further studies will be required to better define the diagnostic performance of these tests.  相似文献   

12.
The primary parasitic relations between the itch mite Sarcoptes scabiei (L.) and man are confirmed indirectly by the presence in the family Sarcoptidae of close genera, members of which parasitize primates. Judging from the composition of domestic and wild animals-hosts, the source of their infection with S. scabiei was man that gave rise to numerous forms of mites specific to individual species of hosts or their related groups belonging to different taxonomic ranks. Three types of host relations and, accordingly, forms of sarcoptosis are suggested at the infection from an alien host: pseudosarcoptosis, temporary self-curable and typical lingering sarcoptosis. The ways of reinfection, invasiveness of stages of the mite and clinical picture for each form of the disease are analyzed.  相似文献   

13.

Background

Follicular stimulating hormone (FSH) is a glycoprotein and widely used for the treatment of infertility; FSH action is mediated by FSH receptor (FSHR), SNPs of which determine the ovarian response. Two polymorphisms of the FSHR gene were identified, which caused a change of threonine (T) to alanine (A) at position 307 and asparagine (N) to serine(S) at position 680. Both polymorphic sites give rise to three discrete variants of the FSHR: TT, TA, and AA for position 307; NN, NS, and SS for position 680.

Methodology/Principal Findings

450 Chinese women were recruited in an assisted reproductive technology program from October 2011 to March 2012. FSHR polymorphisms at the positions 307 and 680 were examined by PCR-RFLP. Serum FSH and estradiol level, FSH amount, ovarian response and pregnancy rate were recorded during treatment. The basal FSH levels were higher in AA [7.38 ± 2.07 vs 6.34 ± 1.75, 6.63 ± 1.94, P<0.05, 95% CI (6.75, 8.01)] and SS [7.51 ± 2.01 vs 6.31 ± 1.75, 6.66 ± 1.96, P<0.05, 95% CI (6.88, 8.15)] compared to other genotypes respectively; the days for ovulation induction was slightly longer in AA and SS. Women with AA and SS have higher rates of poor response compared to carriers of other genotypes (P<0.05). Furthermore, there is a nearly complete linkage between these two polymorphisms in Chinese women (D’=0.95, r2=0.84).

Conclusions/Significance

In Chinese women receiving ART, the subjects with AA and SS genotypes have higher basal FSH levels, and these genotypes are associated with an increased risk of poor response. Our data suggested that the personalized FSH therapy may be applied according to patient’s genetic background in clinical settings. The linkage suggested that the polymorphisms of Thr307Ala and Asn680Ser may be used as TAG-SNP markers for analysis of potential genotyping in ART.  相似文献   

14.

Background

Atherosclerosis is a chronic inflammatory disease mediated by immune cells. Th22 cells are CD4+ T cells that secret IL-22 but not IL-17 or IFN-γ and are implicated in the pathogenesis of inflammatory disease. The roles of Th22 cells in the pathophysiologic procedures of acute coronary syndrome (ACS) remain unclear. The purpose of this study is to investigate the profile of Th22, Th17 and Th17/Th1 cells in ACS patients, including unstable angina (UA) and acute myocardial infarction (AMI) patients.

Design and Methods

In this study, 26 AMI patients, 16 UA patients, 16 stable angina (SA) patients and 16 healthy controls were included. The frequencies of Th22, Th17 and Th17/Th1 cells in AMI, UA, SA patients and healthy controls were examined by flow cytometry. Plasma levels of IL-22, IL-17 and IFN-γ were measured by enzyme-linked immunosorbent assay (ELISA).

Results

Th22, Th17 and Th17/Th1 cells were significantly increased in AMI and UA patients compared with SA patients and healthy controls. Moreover, plasma IL-22 level was significantly elevated in AMI and UA patients. In addition, Th22 cells correlated positively with IL-22 as well as Th17 cells in AMI and UA patients.

Conclusion

Our findings showed increased frequencies of both Th22 and Th17 cells in ACS patients, which suggest that Th22 and Th17 cells may play a potential role in plaque destabilization and the development of ACS.  相似文献   

15.
摘要 目的:探讨慢性牙周炎(CP)合并2型糖尿病(T2DM)患者龈沟液微小核糖核酸(miR)-21、miR-34a表达水平与牙周指标和辅助性T细胞(Th)1/Th2/Th17失衡的关系。方法:选取2020年3月~2022年3月首都医科大学附属北京世纪坛医院口腔科收治的114例CP患者,根据是否合并T2DM分为CP合并T2DM组36例和单纯CP组78例,另选取60名健康体检者为对照组。对比三组牙周指标、龈沟液miR-21、miR-34a表达和外周血Th1、Th2、Th17、Th1/Th2/Th17、血清Th1、Th2、Th17相关细胞因子水平,采用Spearman相关性分析CP合并T2DM患者龈沟液miR-21、miR-34a表达与牙周指标和外周血Th1、Th2、Th17、Th1/Th2/Th17及其相关细胞因子水平的相关性。采用Pearson/Spearman相关性分析CP合并T2DM患者牙周指标与外周血Th1、Th2、Th17、Th1/Th2/Th17及其相关细胞因子水平的相关性。结果:对照组、单纯CP组、CP合并T2DM组菌斑指数(PLI)、牙龈出血指数(BI)、附着丧失(AL)、探诊深度(PD)依次增加,龈沟液miR-21和外周血Th2及血清白细胞介素(IL)-2、干扰素-γ(INF-γ)依次降低,龈沟液miR-34a和外周血Th1、Th17、Th1/Th2/Th17及血清IL-4、IL-10、IL-17、肿瘤坏死因子-α(TNF-α)依次升高(P<0.05)。Spearman相关性分析显示,CP合并T2DM患者龈沟液miR-21表达与PLI、BI、AL、PD和外周血Th1、Th17、Th1/Th2/Th17及血清IL-4、IL-10、IL-17、TNF-α呈负相关,与外周血Th2和血清IL-2、INF-γ呈正相关(P<0.05);而miR-34a则与之相反。Pearson/Spearman相关性分析显示,CP合并T2DM患者PLI、BI、AL、PD与外周血Th1、Th17、Th1/Th2/Th17和血清IL-4、IL-10、IL-17、TNF-α呈正相关,与外周血Th2和血清IL-2、INF-γ呈负相关(P<0.05)。结论:CP合并T2DM患者龈沟液miR-21低表达和miR-34a高表达,与牙周状况差有关,可能通过调节Th1/Th2/Th17失衡参与CP合并T2DM进展。  相似文献   

16.
Mycoplasma arthritidis, an inflammatory murine pathogen, secretes a potent superantigen, Mycoplasma arthritidis mitogen (MAM) that contributes to toxic shock, arthritis and skin necrosis. Previously we showed that MAM induced type 2 T-cell cytokines in mice that express functional TLR2 and TLR4, but type 1 cytokines in mice that lack TLR4 function. We show here that IL-17, pSTAT3 and retinoid-related orphan nuclear receptorγt are rapidly expressed in wild-type C3H/HeSnJ (TLR2+/4+) mice but are significantly delayed in mutant C3H/HeJ (TLR2+/4-) mice. This marked kinetic difference was associated with a high level of IL-6 in TLR2+/4+ mice versus high levels of IL-1β and TNFα in TLR2+/4- mice. Also antibodies to IL-6 and IL-23, suppressed IL-17 responses to MAM in TLR2+/4+ mice whereas anti-IL-1β, but not anti-TNFα, enhanced IL-17 in TLR2+/4- mice. Antibody blocking of TLR4 in TLR2+/4+ mice decreased IL-17 and IL-6 but not IL-23. In addition both IL-17 and IL-6 but not IL-23 were elevated in TLR2 KO mice versus wild-type TLR2+/4+ mice given MAM. We conclude that the MAM interaction with TLR2 versus TLR4 leads to distinct cytokine pathways mediated primarily by IL-1β or IL-6/IL-17 signalling respectively. Our findings suggest that the differential interaction of MAM with different TLRs might play an important role in disease outcomes by M. arthritidis.  相似文献   

17.
摘要 目的:探讨外周血辅助T细胞(Th)1/Th2比值、白介素(IL)-23/Th17轴与中重度斑块状银屑病(PP)患者颈动脉粥样硬化和临床疗效的关系。方法:选取2021年1月~2022年1月徐州医科大学附属医院收治的97例中重度PP患者为中重度PP组,根据颈动脉内中膜厚度(CIMT)分为增厚组39例和正常组58例,根据甲氨蝶呤(MTX)治疗是否应答有效分为无应答组和应答组,另选取同期50例体检健康志愿者为对照组。采用流式细胞术检测外周血Th1、Th2百分比和Th1/Th2比值,酶联免疫吸附法检测外周血IL-23、IL-17A水平。采用Pearson相关性分析中重度PP患者外周血Th1、Th2、Th1/Th2比值和IL-23/Th17轴相关因子与CIMT的相关性,多因素Logistic回归分析中重度PP患者MTX治疗无应答的影响因素。结果:与对照组比较,中重度PP组外周血Th1、Th1/Th2比值、IL-23和IL-17A水平升高,Th2比例降低(P均<0.001)。97例中重度PP患者颈动脉粥样硬化发生率为40.21%(39/97)。与正常组比较,增厚组外周血Th1、Th1/Th2比值、IL-23和IL-17A水平升高,Th2比例降低(P均<0.001)。Pearson相关性分析显示,中重度PP患者外周血Th1、Th1/Th2比值、IL-23、IL-17A与CIMT呈正相关,Th2与CIMT呈负相关(r=0.695、0.706、0.688、0.650、-0.639,P均<0.001)。97例中重度PP患者MTX治疗无应答率为21.65%(21/97)。多因素Logistic回归分析显示,重度PP和Th1、Th1/Th2比值、IL-23、IL-17A升高为中重度PP患者MTX治疗无应答的独立危险因素,Th2升高为独立保护因素(P均<0.05)。结论:中重度PP患者外周血Th1/Th2比值和IL-23/Th17轴相关因子升高,与颈动脉粥样硬化和MTX治疗无应答有关,可能成为中重度PP患者颈动脉粥样硬化和临床疗效评估指标。  相似文献   

18.

Introduction  

T cell abnormalities have been associated with the pathogenesis of systemic sclerosis (SSc). Recently, besides T helper (Th)17 cells, the Th22 subset has been identified in humans. Our purpose was to investigate the pattern of cytokines produced and chemokine-receptors expressed by peripheral blood (PB) Th cells in SSc and healthy donors (HD) focusing on cells producing interleukin (IL)-17 and IL-22 and to identify specific clinical associations.  相似文献   

19.
OBJECTIVES: Several cytokines secreted from breast cancer tissues are suggested to be related to disease prognosis. We examined Th1/Th2/Th17 cytokines produced from three-dimensionally cultured breast cancer tissues and related them with patient clinical profiles. METHODS: 21 tumor tissues and 9 normal tissues surgically resected from breast cancer patients were cultured in thermoreversible gelatin polymer–containing medium. Tissue growth and Th1/Th2/Th17 cytokine concentrations in the culture medium were analyzed and were related with hormone receptor expressions and patient clinical profiles. RESULTS: IL-6 and IL-10 were expressed highly in culture medium of both cancer and normal tissues. However, IFN-γ, TNF-α, IL-2, and IL-17A were not detected in the supernatant of the three-dimensionally cultured normal mammary gland and are seemed to be specific to breast cancer tissues. The growth abilities of hormone receptor–negative cancer tissues were significantly higher than those of receptor-positive tissues (P = 0.0383). Cancer tissues of stage ≥ IIB patients expressed significantly higher TNF-α levels as compared with those of patients with stage < IIB (P = 0.0096). CONCLUSIONS: The tumor tissues resected from breast cancer patients can grow in the three-dimensional thermoreversible gelatin polymer culture system and produce Th1/Th2/Th17 cytokines. Hormone receptor–positive cancer tissues showed less growth ability. TNF-α is suggested to be a biomarker for the cancer stage.  相似文献   

20.
李妍  康辉 《微生物学杂志》2008,28(5):98-101
探讨Th1、Th2和Th17型细胞在类风湿性关节炎(RA)和系统性红斑狼疮(SLE)发病机制中的作用。收集37例RA患者、25例SLE患者和34例健康人的抗凝血,应用ELISA检测血清中IFN-γ、IL-10和IL-17的水平。与健康对照组比较,RA和SLE患者血清中IFN-γ的水平均具有统计学意义(P<0.05);SLE患者IL-10水平出现有意义的升高(P<0.05);而RA患者IL-17的升高具有统计学意义(P<0.05)。由此提示Th1、Th2和Th17细胞在自身免疫性疾病中均发挥不同的重要作用。  相似文献   

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