Browsing by Author "Musselwhite, Laura W"

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    Chagas disease: "the new HIV/AIDS of the Americas".
    (PLoS Negl Trop Dis, 2012) Hotez, Peter J; Dumonteil, Eric; Woc-Colburn, Laila; Serpa, Jose A; Bezek, Sarah; Edwards, Morven S; Hallmark, Camden J; Musselwhite, Laura W; Flink, Benjamin J; Bottazzi, Maria Elena
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    Country of residence is associated with distinct inflammatory biomarker signatures in HIV-infected patients.
    (J Virus Erad, 2017-01-01) Manion, Maura; Andrade, Bruno B; DerSimonian, Rebecca; Gu, Wenjuan; Rupert, Adam; Musselwhite, Laura W; Sierra-Madero, Juan G; Belaunzaran-Zamudio, Pablo F; Sanne, Ian; Lederman, Michael M; Sereti, Irini
    BACKGROUND: Inflammation and coagulation biomarkers are independent predictors of morbidity and mortality in HIV-infected patients. The impact of country of residence on these biomarkers is unknown and was investigated in persons at similar stages of HIV infection. METHODS: Cryopreserved plasma specimens were analysed from 267 ART-naive patients with CD4 cell counts <100 cells/μl from Mexico (n=124) and South Africa (n=143). Biomarkers were compared and dimension reduction analyses were performed to highlight biosignatures according to nationality, gender and tuberculosis co-infection. RESULTS: Mexican patients were significantly different from South Africans with regard to age, gender, CD4 cell count, haemoglobin, presence of AIDS-defining illness and prevalence of active tuberculosis. After adjusting for baseline characteristics, patients from Mexico had higher levels of IFN-γ, IL-8, and CXCL-10 whereas patients from South Africa had higher levels of fibrinogen, LTB4, P-selectin, protein S, and sCD40 ligand. The effect of country on the profile of biomarker expression was stronger than gender differences and tuberculosis co-infection. CONCLUSION: Inflammation and coagulation biomarkers vary significantly by country. Further studies are needed to evaluate how these differences may contribute to HIV pathogenesis and prognosis in diverse populations and how they can be accounted for in studies using biomarkers as surrogate end points.
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    IL-10, IL-15, IL-17, and GMCSF levels in cervical cancer tissue of Tanzanian women infected with HPV16/18 vs. non-HPV16/18 genotypes.
    (Infect Agent Cancer, 2015) Vidal, Adriana C; Skaar, David; Maguire, Rachel; Dodor, Seyram; Musselwhite, Laura W; Bartlett, John A; Oneko, Olola; Obure, Joseph; Mlay, Pendo; Murphy, Susan K; Hoyo, Cathrine
    BACKGROUND: Despite comparable screening rates for precancerous lesions, higher incidence and mortality related to cervical cancer in minority women persists. Recent evidence suggests that minority women with precancerous cervical lesions harbor a wider range of human papillomavirus (HPV) genotypes, many of these distinct from HPV16/18, those most commonly found in Caucasian women. The goal of the analysis was to determine if inflammatory cytokines and chemokines varied by HPV 16/18 versus other genotypes in cervical cancer tissues from Tanzanian women. METHODS: HPV genotypes and concentrations of chemokines and cytokines were measured from homogenized fresh tumor tissue of thirty-one women with invasive cervical cancer (ICC). Risk factors for cervical cancer including age, parity, hormonal contraceptive use and cigarette smoking were obtained by questionnaire. Generalized linear models were used to evaluate differences between chemokines/cytokine levels in women infected with HPV16/18 and those infected with other HPV genotypes. RESULTS: After adjusting for age, parity and hormonal contraceptives, IL-17 was found significantly more frequently in invasive cervical cancer samples of women infected with HPV16/18 compared to women infected with other HPV genotypes (p = 0.033). In contrast, higher levels for granular macrophage colony-stimulating factor (p = 0.004), IL-10 (p = 0.037), and IL-15 (p = 0.041) were found in ICC tissues of women infected with genotypes other than HPV16/18 when compared to those of women infected with HPV16/18. CONCLUSIONS: While the small sample size limits inference, our data suggest that infection with different HPV genotypes is associated with distinct pro-inflammatory cytokine expression profiles; whether this explains some of the racial differences observed in cervical cancer is still unclear. Future studies are needed to confirm these findings.
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    Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndrome.
    (Blood, 2012-11-29) Funderburg, Nicholas T; Zidar, David A; Shive, Carey; Lioi, Anthony; Mudd, Joseph; Musselwhite, Laura W; Simon, Daniel I; Costa, Marco A; Rodriguez, Benigno; Sieg, Scott F; Lederman, Michael M
    The mechanisms responsible for increased cardiovascular risk associated with HIV-1 infection are incompletely defined. Using flow cytometry, in the present study, we examined activation phenotypes of monocyte subpopulations in patients with HIV-1 infection or acute coronary syndrome to find common cellular profiles. Nonclassic (CD14(+)CD16(++)) and intermediate (CD14(++)CD16(+)) monocytes are proportionally increased and express high levels of tissue factor and CD62P in HIV-1 infection. These proportions are related to viremia, T-cell activation, and plasma levels of IL-6. In vitro exposure of whole blood samples from uninfected control donors to lipopolysaccharide increased surface tissue factor expression on all monocyte subsets, but exposure to HIV-1 resulted in activation only of nonclassic monocytes. Remarkably, the profile of monocyte activation in uncontrolled HIV-1 disease mirrors that of acute coronary syndrome in uninfected persons. Therefore, drivers of immune activation and inflammation in HIV-1 disease may alter monocyte subpopulations and activation phenotype, contributing to a pro-atherothrombotic state that may drive cardiovascular risk in HIV-1 infection.
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    Vitamin D, D-dimer, Interferon γ, and sCD14 Levels are Independently Associated with Immune Reconstitution Inflammatory Syndrome: A Prospective, International Study
    (EBioMedicine, 2016-02-01) Musselwhite, Laura W; Andrade, Bruno B; Ellenberg, Susan S; Tierney, Ann; Belaunzaran-Zamudio, Pablo F; Rupert, Adam; Lederman, Michael M; Sanne, Ian; Sierra Madero, Juan G; Sereti, Irini
    © 2015To determine the immunological profile most important for IRIS prediction, we evaluated 20 baseline plasma biomarkers in Acquired Immunodeficiency Syndrome (AIDS) patients initiating antiretroviral therapy (ART). Patients were enrolled in a randomized, placebo-controlled ART initiation trial in South Africa and Mexico to test whether maraviroc could prevent IRIS. Participants were classified prospectively as having IRIS within 6 months of ART initiation. Twenty plasma biomarkers were measured at study enrollment for 267 participants. Biomarkers were tested for predicting IRIS with adjustment for covariates chosen through forward stepwise selection. Sixty-two participants developed IRIS and of these 19 were tuberculosis (TB)-IRIS. Baseline levels of vitamin D and higher D-dimer, interferon gamma (IFNγ), and sCD14 were independently associated with risk of IRIS in multivariate analyses. TB-IRIS cases exhibited a distinct biosignature from IRIS related to other pathogens, with increased levels of C-reactive protein (CRP), sCD14, IFNγ, and lower levels of Hb that could be captured by a composite risk score. Elevated markers of Type 1 T helper (Th1) response, monocyte activation, coagulation and low vitamin D were independently associated with IRIS risk. Interventions that decrease immune activation and increase vitamin D levels warrant further study.