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Sökning: WFRF:(Grankvist Anna)

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1.
  • Eimer, Johannes, et al. (författare)
  • Spiroplasma ixodetis Infections in Immunocompetent and Immunosuppressed Patients after Tick Exposure, Sweden
  • 2022
  • Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 28:8, s. 1681-1685
  • Tidskriftsartikel (refereegranskat)abstract
    • We report 2 cases of Spiroplasma ixodetis infection in an immunocompetent patient and an immunocompromised patient who had frequent tick exposure. Fever, thrombocytopenia, and increased liver aminotransferase levels raised the suspicion of anaplasmosis, but 16S rRNA PCR and Sanger sequencing yielded a diagnosis of spiroplasmosis. Both patients recovered after doxycycline treatment.
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2.
  • Aberšek, Nina, et al. (författare)
  • Calprotectin levels in amniotic fluid in relation to intra-amniotic inflammation and infection in women with preterm labor with intact membranes: A retrospective cohort study
  • 2022
  • Ingår i: European Journal of Obstetrics & Gynecology and Reproductive Biology. - : Elsevier BV. - 1872-7654 .- 0301-2115. ; 272, s. 24-29
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate the concentrations of calprotectin in amniotic fluid with respect to intra-amniotic inflammation and infection and to assess the presence or absence of bacteria in the amnio-chorionic niche with respect to presence or absence of intra-amniotic inflammation. Study design: Seventy-nine women with singleton pregnancies and preterm labor with intact membranes (PTL) were included in the study. Amniotic fluid was collected at the time of admission by amniocentesis and calprotectin levels were analyzed from frozen/thawed samples using ELISA. Interleukin (IL)-6 concentration was measured by point-of-care test. Samples from amniotic fluid and the amnio-chorionic niche (space between amniotic and chorionic membranes) were microbiologically analyzed. Microbial invasion of the amniotic cavity (MIAC) was diagnosed based on a positive PCR result for Ureaplasma species, Mycoplasma hominis, 16S rRNA or positive culture. Intra-amniotic inflammation (IAI) was defined as amniotic fluid point-of-care IL-6 concentration ≥ 745 pg/mL. The cohort of included women was divided into 4 subgroups based on the presence or absence of IAI/MIAC; i) intra-amniotic infection, ii) sterile IAI, iii) intra-amniotic colonization and iv) neither MIAC nor IAI. Results: Women with intra-amniotic infection had a significantly higher intra-amniotic calprotectin concentration (median; 101.6 µg/mL) compared with women with sterile IAI (median; 9.2 µg/mL), women with intra-amniotic colonization (median; 2.6 µg/mL) and women with neither MIAC nor IAI (median 4.6 µg/mL) (p = 0.001). Moreover, significantly higher amniotic fluid calprotectin concentration was seen in women who delivered within 7 days (p = 0.003). A significant negative correlation was found between amniotic fluid calprotectin and gestational age at delivery (rho = 0.32, p = 0.003). Relatively more bacteria in the amnio-chorionic niche were found in the sterile IAI group compared with the other groups. Conclusions: Calprotectin concentrations in amniotic fluid were significantly higher in the intra-amniotic infection group compared with the other groups. Moreover, the bacterial presence in the amnio-chorionic niche was higher in IAI group.
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4.
  • Dadgar, A., et al. (författare)
  • Fever of unknown origin in a multiple sclerosis patient on immunomodulatory therapy was due to neoehrlichiosis
  • 2017
  • Ingår i: Läkartidningen. - 0023-7205. ; 114:38
  • Tidskriftsartikel (refereegranskat)abstract
    • The emerging tick-borne bacterium Candidatus Neoehrlichia mikurensis is the etiologic agent of neoehrlichiosis, a febrile illness that may be accompanied by vascular complications. Severe cases of neoehrlichiosis have been described in patients with hematologic malignancies and systemic rheumatic diseases. We present the first case of neoehrlichiosis in a patient with multiple sclerosis undergoing rituximab therapy. © 2017, Swedish Medical Association. All rights reserved.
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5.
  • Darsalia, Vladimer, et al. (författare)
  • Glucagon-like peptide-1 receptor activation reduces ischaemic brain damage following stroke in Type 2 diabetic rats
  • 2012
  • Ingår i: Clinical Science. - : Portland Press. - 0143-5221 .- 1470-8736. ; 122:9-10, s. 473-483
  • Tidskriftsartikel (refereegranskat)abstract
    • Diabetes is a strong risk factor for premature and severe stroke. The GLP-IR (glucagon-like peptide-1 receptor) agonist Ex-4 (exendin-4) is a drug for the treatment of T2D (Type 2 diabetes) that may also have neuroprotective effects. The aim of the present study was to determine the efficacy of Ex-4 against stroke in diabetes by using a diabetic animal model, a drug administration paradigm and a dose that mimics a diabetic patient on Ex-4 therapy. Furthermore, we investigated inflammation and neurogenesis as potential cellular mechanisms underlying the Ex-4 efficacy. A total of seven 9-month-old Type 2 diabetic Goto-Kakizaki rats were treated peripherally for 4 weeks with Ex-4 at 0.1, 1 or 5 mu g/kg of body weight before inducing stroke by transient middle cerebral artery occlusion and for 2-4 weeks thereafter. The severity of ischaemic damage was measured by evaluation of stroke volume and by stereological counting of neurons in the striatum and cortex. We also quantitatively evaluated stroke-induced inflammation, stem cell proliferation and neurogenesis. We show a profound anti-stroke efficacy of the clinical dose of Ex-4 in diabetic rats, an arrested microglia infiltration and an increase of stroke-induced neural stem cell proliferation and neuroblast formation, while stroke-induced neurogenesis was not affected by Ex-4. The results show a pronounced anti-stroke, neuroprotective and anti-inflammatory effect of peripheral and chronic Ex-4 treatment in middle-aged diabetic animals in a preclinical setting that has the potential to mimic the clinical treatment. Our results should provide strong impetus to further investigate GLP-IR agonists for their neuroprotective action in diabetes, and for their possible use as anti-stroke medication in non-diabetic conditions.
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7.
  • Grankvist, Anna (författare)
  • Candidatus Neoehrlichia mikurensis - a new agent of tick-borne infectious disease
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • “Candidatus Neoehrlichia mikurensis” (Ca. N. mikurensis) is a tick-borne bacterial pathogen that can cause disease particularly among immune compromised persons. This new infectious disease is called neoehrlichiosis. The clinical picture of neoehrlichios is characterized by fever, migrating pain, and vascular/thromboembolic complications. The bacterium received its name in 2004, after its discovery in ticks and rodents on the Japanese island of Mikura. This thesis have four main aims 1) Map this new infectious disease with respect to what types of patients that are afflicted, the clinical picture displayed by the patient categories, and the pattern of laboratory findings seen in infected patients. This is described in paper I; where clinical data of six patients participating in the “NEO-VÄST study” are described together with additional cases from Europe. 2) Determine if Ca. N. mikurensis is an opportunist that only afflicts immune compromised patients? In paper II we describe two immune competent patients who had raised levels of Ca. N. mikurensis DNA in the blood accompanied by a cytokine response for several months. The patients were diagnosed after PCR screening of plasma samples from 102 tick-bitten persons in Sweden who participated in the Tick-Borne Disease Study called STING. A PCR assay for clinical use was developed in this study and the cytokine levels were measured with multiplex technology. 3) Establish if Ca. N. mikurensis strains in Europe vary genetically. Paper III describes the development and use of a multilocus sequence analysis (MLSA) protocol to investigate the genetic diversity of clinical Ca. N. mikurensis strains in Europe. A low genetic diversity was seen among the strains, all of which were derived from immune compromised patients. Unexpectedly, Ehrlichia ruminantium was found to be the closest relative of Ca. N. mikurensis within the family of Anaplasmataceae. 4) Perform de novo whole-genome sequenc-ing of Ca. N. mikurensis to characterize the bacterium. In paper IV we determined the complete reference genome sequence of Ca. N. mikurensis, sequenced directly from the blood of three immune suppressed patients. We also compared these sequences with those of other whole-genome sequenced relatives of Ca. N. mikurensis. The sequencing strategy relied on library preparation using a new type of technology called 10X Chromium followed by Hiseq Illumina sequencing, sequence assembly and de novo annotation. Our studies have yielded more knowledge about this anonymous emerging pathogen but much remains to be resolved, the work continues!
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8.
  • Grankvist, Anna, et al. (författare)
  • Infections with Candidatus Neoehrlichia mikurensis and Cytokine Responses in 2 Persons Bitten by Ticks, Sweden
  • 2015
  • Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 21:8, s. 1462-1465
  • Tidskriftsartikel (refereegranskat)abstract
    • The prevalence of Candidatus Neoehrlichia mikurensis infection was determined in 102 persons bitten by ticks in Sweden. Two infected women had erythematous rashes; 1 was co-infected with a Borrelia sp., and the other showed seroconversion for Anaplasma phagocytophilum. Both patients had increased levels of Neoehrlichia DNA and serum cytokines for several months.
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9.
  • Grankvist, Anna, et al. (författare)
  • Infections With the Tick-Borne Bacterium "Candidatus Neoehrlichia mikurensis" Mimic Noninfectious Conditions in Patients With B Cell Malignancies or Autoimmune Diseases
  • 2014
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 58:12, s. 1716-1722
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Candidatus Neoehrlichia mikurensis is a newly discovered noncultivatable bacterium spread among ticks and rodents in Europe and Asia that can infect humans, particularly immunocompromised patients. Methods.aEuro integral We compiled clinical and laboratory data from 11 patients with hematological malignances or autoimmune diseases who were diagnosed with Candidatus N. mikurensis infection in Europe 2010-2013. Both published (6) and unpublished cases (5) were included. Results.aEuro integral The patients had a median age of 67, were mostly male (8/11), and resided in Sweden, Switzerland, Germany, and the Czech Republic. All but one had ongoing or recent immune suppressive treatment and a majority were splenectomized (8/11). Less than half of them recalled tick exposure. The most frequent symptoms were fever (11/11), localized pain afflicting muscles and/or joints (8/11), vascular and thromboembolic events (6/11), that is, deep vein thrombosis (4), transitory ischemic attacks (2), pulmonary embolism (1), and arterial aneurysm (1). Typical laboratory findings were elevated C-reactive protein, leukocytosis with neutrophilia, and anemia. Median time from onset of symptoms to correct diagnosis was 2 months. In at least 4 cases, the condition was interpreted to be due to the underlying disease, and immunosuppressive therapy was scheduled. All patients recovered completely when doxycycline was administered. Conclusions.aEuro integral Candidatus N. mikurensis is an emerging tick-borne pathogen that may give rise to a systemic inflammatory syndrome in persons with hematologic or autoimmune diseases that could be mistaken for recurrence of the underlying disease and/or unrelated arteriosclerotic vascular events. Awareness of this new pathogen is warranted among rheumatologists, hematologists, oncologists, and infectious disease specialists.
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10.
  • Grankvist, Anna, et al. (författare)
  • Multi-locus sequence analysis (MLSA) of clinical "CandidatusNeoehrlichia mikurensis" strains from Europe.
  • 2015
  • Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 53:10, s. 3126-3132
  • Tidskriftsartikel (refereegranskat)abstract
    • CandidatusNeoehrlichia mikurensis is the tick-borne agent of neoehrlichiosis, an infectious disease that primarily affects immunocompromised patients. So far, the genetic variability of Neoehrlichia has been studied only by comparing 16S rRNA gene and groEL operon sequences. We describe the development and use of a multi-locus sequence analysis (MLSA) protocol to characterize the genetic diversity of clinicalNeoehrlichiastrains in Europe and their relatedness to other species within the Anaplasmataceae family.Six genes were selected:ftsZ, clpB, gatB,lipA,groEL and 16SrRNA. Each MLSA locus was amplified by real-time PCR, and the PCR-products sequenced. Phylogenetic trees of MLSA locus relatedness were constructed from aligned sequences. Blood samples from 12 patients with confirmed Neoehrlichia infection from Sweden (n = 9), the Czech Republic (n = 2) and Germany (n = 1) were analyzed with the MLSA protocol.Threeof the Swedish strains exhibited identical lipA sequences, while the lipA sequences of the strains from the other nine patients were identical to each other.One of the Czech strains had one differing nucleotide in the clpB sequence from the sequences of the other 11 strains. All 12 strains had identical sequences for the genes 16SrRNA,ftsZ, gatB, and groEL.According to the MLSA, Neoehrlichia is most closely related to E. ruminantium, less so to A. phagocytophilum and least to Wolbachiaendosymbiont, among the Anaplasmataceae.To conclude, three sequence types of infectious Neoehrlichia wereidentified: one in the west of Sweden, one in the Czech Republic, and one spread throughout Europe.
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11.
  • Grankvist, Anna, et al. (författare)
  • Multilocus sequence analysis of clinical "candidatus neoehrlichia mikurensis" strains from Europe
  • 2015
  • Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 53:10, s. 3126-3132
  • Tidskriftsartikel (refereegranskat)abstract
    • Copyright © 2015, American Society for Microbiology. All Rights Reserved. Candidatus Neoehrlichia mikurensis" is the tick-borne agent of neoehrlichiosis, an infectious disease that primarily affects immunocompromised patients. So far, the genetic variability of "Ca. Neoehrlichia" has been studied only by comparing 16S rRNA genes and groEL operon sequences. We describe the development and use of a multilocus sequence analysis (MLSA) protocol to characterize the genetic diversity of clinical "Ca. Neoehrlichia" strains in Europe and their relatedness to other species within the Anaplasmataceae family. Six genes were selected: ftsZ, clpB, gatB, lipA, groEL, and 16S rRNA. Each MLSA locus was amplified by real-time PCR, and the PCR products were sequenced. Phylogenetic trees of MLSA locus relatedness were constructed from aligned sequences. Blood samples from 12 patients with confirmed "Ca. Neoehrlichia" infection from Sweden (n9), the Czech Republic (n2), and Germany (n1) were analyzed with the MLSA protocol. Three of the Swedish strains exhibited identical lipA sequences, while the lipA sequences of the strains from the other nine patients were identical to each other. One of the Czech strains had one differing nucleotide in the clpB sequence from the sequences of the other 11 strains. All 12 strains had identical sequences for the genes 16S rRNA, ftsZ, gatB, and groEL. According to the MLSA, among the Anaplasmataceae, "Ca. Neoehrlichia" is most closely related to Ehrlichia ruminantium, less so to Anaplasma phagocytophilum, and least to Wolbachia endosymbionts. To conclude, three sequence types of infectious "Ca. Neoehrlichia" were identified: one in the west of Sweden, one in the Czech Republic, and one spread throughout Europe.
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12.
  • Hammarström, Helena, et al. (författare)
  • Serum-based diagnosis of Pneumocystis pneumonia by detection of Pneumocystis jirovecii DNA and 1,3-beta-D-glucan in HIV-infected patients: a retrospective case control study
  • 2019
  • Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPneumocystis jirovecii pneumonia (PCP) is one of the most common HIV-related opportunistic infections. The diagnosis of PCP is based on analyses from respiratory tract specimens which may require the invasive procedure of a diagnostic bronchoscopy. The objective of this study was to evaluate the diagnostic potential of Pneumocystis jirovecii PCR in serum combined with the 1,3-beta-D-glucan (betaglucan) test for the diagnosis of PCP in HIV-infected patients.MethodsThis was a retrospective case-control study including serum samples from 26 HIV-infected patients with PCP collected within 5days prior to the start of PCP treatment, 21 HIV-infected control subjects matched by blood CD4(+) cell counts, and 18 blood donors. The serum samples were analyzed for Pneumocystis jirovecii PCR and betaglucan. The reference standard for PCP was based on previously described microbiological and clinical criteria.ResultsAll patients with PCP had detectabe Pneumocystis jirovecii DNA in serum yielding a sensitivity for the Pneumocystis jirovecii PCR assay in serum of 100%. All blood donors had negative Pneumocystis PCR in serum. The specificity when testing HIV-infected patients was 71%, but with a PCR Cycle threshold (Ct) value of 34 as cut-off the specificity was 90%. At a putative pretest probaility of 20%, the negative and positive predictive value for the Pneumocystis PCR assay in serum was 0.99 and 0.71, respectively. Betaglucan with cut-off level 200pg/ml combined with a positive Pneumocystis jirovecii PCR result had sensitivity and specificity of 92 and 90%, respectively. The concentration of Pneumocystis jirovecii DNA in serum samples, expressed by the PCR Ct values, correlated inversely to the betaglucan levels in serum.ConclusionIn this case-control study including 70% of all HIV-infected patients with PCP treated at Sahlgrenska University Hospital during a time period of 13years, Pneumocystis PCR analysis on serum samples had a very high sensitivity and negative predictive value for the diagnosis of PCP in HIV-infected patients. A serum-based diagnostic procedure either based on Pneumocystis jirovecii PCR alone or in combination with betaglucan analysis may thus be feasible and would facilitate the care of HIV-infected patients with suspected PCP.
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13.
  • Höper, Linnea, et al. (författare)
  • Vasculitis due to Candidatus Neoehrlichia mikurensis : a cohort study of 40 Swedish patients
  • 2021
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 73:7, s. e2372-e2378
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Candidatus (Ca.) Neoehrlichia (N.) mikurensis is an emerging tick-borne pathogen of humans that is closely related to Ehrlichia and Anaplasma species. This strict intracellular bacterium escapes detection by routine microbiologic diagnostic methods such as blood culture leading to considerable under-diagnosis of the infectious disease it causes, neoehrlichiosis.METHODS: Here, we describe the vascular and thromboembolic events afflicting a series of 40 patients diagnosed with neoehrlichiosis in Sweden during a 10-year period (2009-2019).RESULTS: The majority of the patients (60%) developed vascular events ranging from repeated thrombophlebitis, deep vein thrombosis, pulmonary embolism, transitory ischemic attacks to arteritis. Younger age was a risk factor for vascular complications. In contrast, there was no difference in the incidence of vascular events between immunosuppressed and immunocompetent patients. However, there were qualitative differences such that deep vein thrombosis exclusively afflicted the immunosuppressed patients whereas arteritis was restricted to the immunocompetent ones. We also present the case histories of two patients who developed vasculitis mimicking polyarteritis nodosa and giant cell arteritis. Both were cured by doxycycline treatment.CONCLUSIONS: Ca. N. mikurensis infection should be considered in patients living in tick-endemic areas of Europe and northern Asia who present with atypical vascular and/or thromboembolic events. Early diagnosis and antibiotics targeting this emerging infectious agent can eradicate the infection and prevent the development of new vascular events.
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14.
  • Nilsson, Monica, 1955-, et al. (författare)
  • Lek, lärande och lycka : lekande och utforskande i förskolan
  • 2018
  • Bok (övrigt vetenskapligt/konstnärligt)abstract
    • Vad händer när lek, som inspireras av kultur, estetik och pedagogers rollgestaltningar, möter utforskande projektarbete? Vilka utmaningar och möjligheter till växande, lärande, glädje och samvaro innebär det för barn och pedagoger i förskolan? Vilka möjligheter till utveckling av förskolans verksamhet kan det innebära och kan det förstås som undervisning?I den här boken beskrivs hur förskollärare och forskare tillsammans planerar, genomför och reflekterar över en förskoledidaktik som önskar leva upp till läroplanens intentioner om en verksamhet som är rolig, trygg och lärorik för alla barn, men också för pedagogerna.Boken är en beskrivning av ett forskningsprojekt där vad som kallas lekvärldar introducerades i en förskola vars verksamhet är starkt inspirerad av Reggio Emilia-pedagogikens utforskande arbetssätt. Författarna ger en översikt av internationell forskning om lek inom olika discipliner. De diskuterar lekens ställning i förskolan och beskriver olika former av lek. Forskning om pedagogers olika förhållningssätt till lek redovisas och problematiseras också.
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15.
  • Quarsten, H., et al. (författare)
  • Candidatus Neoehrlichia mikurensis and Borrelia burgdorferi sensu lato detected in the blood of Norwegian patients with erythema migrans
  • 2017
  • Ingår i: Ticks and Tick-Borne Diseases. - : Elsevier BV. - 1877-959X. ; 8:5, s. 715-720
  • Tidskriftsartikel (refereegranskat)abstract
    • The most common tick-borne human disease in Norway is Lyme borreliosis. Ticks in Norway also harbour less known disease-causing agents such as Candidatus Neoehrlichia mikurensis, Borrelia miyamotoi and Rickettsia heivetica. However, human infections caused by these pathogens have never been described in Norway. The main aims of the study were to evaluate the contribution of several tick-borne bacterial agents, other than Borrelia burgdorferi sensu lato, to zoonotic diseases in Norway and to determine their clinical pictures. Blood samples from 70 symptomatic tick-bitten adults from the Agder counties in southern Norway were screened for seven tick-borne pathogens by using a commercial multiplex PCR-based method and by singleplex real-time PCR protocols. Most patients (65/70) presented with a rash clinically diagnosed as erythema migrans (EM). The most frequently detected pathogen DNA was from Ca. N. mikurensis and was found in the blood of 10% (7/70) of the patients. The Ca. N. mikurensis-infected patients presented with an EM-like rash as the only symptom. B. burgdorferi s.l. DNA was present in the blood of 4% (3/70) of the study participants. None had detectable Anaplasma phagocytophilum, B. miyamotoi, Rickettsia typhus group or spotted fever group, Francisella tularensis, Coxiella burnetii or Battonella spp. DNA in the blood. The commercially available multiplex PCR bacteria flow chip system failed to identify half of the infected patients detected by corresponding real-time PCR protocols. The recovery of Ca. N. mikurensis DNA was higher in the pellet/plasma fraction of blood than from whole blood. To conclude, Co.. N. mikurensis appeared to be the etiological agent in patients with EM in a surprisingly large fraction of tick-bitten persons in the southern part of Norway.
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16.
  • Späth, Florentin, et al. (författare)
  • Pre-diagnostic serum levels of EGFR and ErbB2 and genetic glioma risk variants : a nested case-control study
  • 2016
  • Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1010-4283 .- 1423-0380. ; 37:8, s. 11065-11072
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variants have been associated with the risk of developing glioma, but functional mechanisms on disease phenotypic traits remain to be investigated. One phenotypic trait of glioblastoma is the mutation and amplification of the epidermal growth factor receptor (EGFR) gene. We investigated associations between pre-diagnostic serum protein concentrations of EGFR and ErbB2, both members of the EGFR family, and future risk of glioma. Further, we studied if EGFR glioma risk variants were associated with EGFR and ErbB2 serum levels. We assessed the associations between genetic glioma risk variants and serum concentrations of EGFR and ErbB2, as measured in pre-diagnostic cohort serum samples of 593 glioma patients and 590 matched cancer-free controls. High serum EGFR and ErbB2 levels were associated with risk of developing glioblastoma (P = 0.008; OR = 1.58, 95 % CI = 1.13-2.22 and P = 0.017, OR = 1.63, 95 % CI = 1.09-2.44, respectively). High serum ErbB2 concentration was also associated with glioma risk overall (P = 0.049; OR = 1.39, 95 % CI = 1.00-1.93). Glioma risk variants were not associated with high serum protein abundance. In contrast, the EGFR risk variant rs4947986 (T) was correlated with decreased EGFR serum levels (study cohort P = 0.024 and controls P = 0.009). To our knowledge, this is the first study showing an association of EGFR and ErbB2 serum levels with glioma more than a decade before diagnosis, indicating that EGFR and ErbB2 serum proteins are important in early gliomagenesis. However, we did not find evidence that glioma risk variants were associated with high pre-diagnostic serum concentrations of EGFR and ErbB2.
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17.
  • Wass, Linda, et al. (författare)
  • Cultivation of the causative agent of human neoehrlichiosis from clinical isolates identifies vascular endothelium as a target of infection.
  • 2019
  • Ingår i: Emerging microbes & infections. - : Informa UK Limited. - 2222-1751. ; 8:1, s. 413-425
  • Tidskriftsartikel (refereegranskat)abstract
    • Candidatus (Ca.) Neoehrlichia mikurensis is the cause of neoehrlichiosis, an emerging tick-borne infectious disease characterized by fever and vascular events. The bacterium belongs to the Anaplasmataceae, a family of obligate intracellular pathogens, but has not previously been cultivated, and it is uncertain which cell types it infects. The goals of this study were to cultivate Ca. N. mikurensis in cell lines and to identify possible target cells for human infection. Blood components derived from infected patients were inoculated into cell lines of both tick and human origin. Bacterial growth in the cell cultures was monitored by real-time PCR and imaging flow cytometry. Ca. N. mikurensis was successfully propagated from the blood of immunocompromised neoehrlichiosis patients in two Ixodes spp. tick cell lines following incubation periods of 7-20 weeks. Human primary endothelial cells derived from skin microvasculature as well as pulmonary artery were also susceptible to infection with tick cell-derived bacteria. Finally, Ca. N. mikurensis was visualized within circulating endothelial cells of two neoehrlichiosis patients. To conclude, we report the first successful isolation and propagation of Ca. N. mikurensis from clinical isolates and identify human vascular endothelial cells as a target of infection.
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18.
  • Wass, Linda, et al. (författare)
  • Serological reactivity to Anaplasma phagocytophilum in neoehrlichiosis patients
  • 2018
  • Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 37:9, s. 1673-1678
  • Tidskriftsartikel (refereegranskat)abstract
    • The tick-borne bacterium Candidatus (Ca.) Neoehrlichia (N.) mikurensis is a cause of "fever of unknown origin" because this strict intracellular pathogen escapes detection by routine blood cultures. Case reports suggest that neoehrlichiosis patients may display serological reactivity to Anaplasma (A.) phagocytophilum. Since Anaplasma serology is part of the diagnostic work-up of undetermined fever in European tick-exposed patients, we wanted to investigate (1) the prevalence of A. phagocytophilum seropositivity among neoehrlichiosis patients, (2) the frequency of misdiagnosed neoehrlichiosis patients among A. phagocytophilum seropositive patients, and (3) the frequency of A. phagocytophilum and Ca. N. mikurensis co-infections. Neoehrlichiosis patients (n = 18) were analyzed for A. phagocytophilum IgM and IgG serum antibodies by indirect immunofluorescence assay. Serum samples from suspected anaplasmosis patients (n = 101) were analyzed for bacterial DNA contents by singleplex PCR specific for A. phagocytophilum and Ca. N. mikurensis, respectively. One fifth of the neoehrlichiosis patients (4/18) were seropositive for IgM and/or IgG to A. phagocytophilum at the time of diagnosis. Among the patients with suspected anaplasmosis, 2% (2/101) were positive for Ca. N. mikurensis by PCR whereas none (0/101) had detectable A. phagocytophilum DNA in the serum. To conclude, patients with suspected anaplasmosis may in fact have neoehrlichiosis. We found no evidence of A. phagocytophilum and Ca. N. mikurensis co-infections in humans with suspected anaplasmosis or confirmed neoehrlichiosis.
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