Development of a low-cost, insect larvae-derived recombinant subunit vaccine against RHDV

Vaccine antigens against rabbit hemorrhagic disease virus (RHDV) are currently derived from inactivated RHDV obtained from livers of experimentally infected rabbits. Several RHDV-derived recombinant immunogens have been reported. However, their application in vaccines has been restricted due to their high production costs. In this paper, we describe the development of an inexpensive, safe, stable vaccine antigen for RHDV. A baculovirus expressing a recombinant RHDV capsid protein (VP60r) was used to infect Trichoplusia ni insect larvae. It reached an expression efficiency of 12.5% of total soluble protein, i.e. ∼ 2 mg of VP60r per larva. Preservation of the antigenicity and immunogenicity of the VP60r was confirmed by immunological and immunization experiments. Lyophilized crude larvae extracts, containing VP60r, were stable, at room temperature, for at least 800 days. In all cases, rabbits immunized with a single dose of VP60r by the intramuscular route were protected against RHDV challenge. Doses used were as low as 2 μg of VP60r in the presence of adjuvant or 100 μg without one. Orally administered VP60r in the absence of an adjuvant gave no protection. The potential costs of an RHDV vaccine made using this technology would be reduced considerably compared with producing the same protein in insect cells maintained by fermentation. In conclusion, the larva expression system may provide a broad-based strategy for production of recombinant subunit antigens (insectigens) for human or animal medicines, especially when production costs restrain their use. © 2007 Elsevier Inc. All rights reserved

The influence of single nucleotide polymorphisms of NOD2 or CD14 on the risk of Mycobacterium tuberculosis diseases: a systematic review

Abstract Background Tuberculosis (TB) is still one of the leading causes of death worldwide. Genetic studies have pointed to the relevance of the NOD2 and CD14 polymorphic alleles in association with the risk of diseases caused by Mycobacterium tuberculosis (Mtb) infection. Methods A systematic review was performed on PubMed, EMBASE, Scientific Electronic Library Online (SciELO), and Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) to examine the association between single nucleotide polymorphisms (SNP) and risk of Mtb diseases. Study quality was evaluated using the Newcastle-Ottawa Quality Scale (NOQS), and the linkage disequilibrium was calculated for all SNPs using a webtool (Package LDpop). Results Thirteen studies matched the selection criteria. Of those, 9 investigated CD14 SNPs, and 6 reported a significant association between the T allele and TT genotypes of the rs2569190 SNP and increased risk of Mtb diseases. The genotype CC was found to be protective against TB disease. Furthermore, in two studies, the CD14 rs2569191 SNP with the G allele was significantly associated with increased risk of Mtb diseases. Four studies reported data uncovering the relationship between NOD2 SNPs and risk of Mtb diseases, with two reporting significant associations of rs1861759 and rs7194886 and higher risk of Mtb diseases in a Chinese Han population. Paradoxically, minor allele carriers (CG or GG) of rs2066842 and rs2066844 NOD2 SNPs were associated with lower risk of Mtb diseases in African Americans. Conclusions The CD14 rs2569190 and rs2569191 polymorphisms may influence risk of Mtb diseases depending on the allele. Furthermore, there is significant association between NOD2 SNPs rs1861759 and rs7194886 and augmented risk of Mtb diseases, especially in persons of Chinese ethnicity. The referred polymorphisms of CD14 and NOD2 genes likely play an important role in risk of Mtb diseases and pathology and may be affected by ethnicity. Systematic review registration CRD4202018652

Systemic Inflammation Associated with Immune Reconstitution Inflammatory Syndrome in Persons Living with HIV

Antiretroviral therapy (ART) has represented a major advancement in the care of people living with HIV (PLWHH), resulting in significant reductions in morbidity and mortality through immune reconstitution and attenuation of homeostatic disruption. Importantly, restoration of immune function in PLWH with opportunistic infections occasionally leads to an intense and uncontrolled cytokine storm following ART initiation known as immune reconstitution inflammatory syndrome (IRIS). IRIS occurrence is associated with the severe and rapid clinical deterioration that results in significant morbidity and mortality. Here, we detail the determinants underlying IRIS development in PLWH, compiling the available knowledge in the field to highlight details of the inflammatory responses in IRIS associated with the most commonly reported opportunistic pathogens. This review also highlights gaps in the understanding of IRIS pathogenesis and summarizes therapeutic strategies that have been used for IRIS

Systemic Inflammation Associated with Immune Reconstitution Inflammatory Syndrome in Persons Living with HIV

Antiretroviral therapy (ART) has represented a major advancement in the care of people living with HIV (PLWHH), resulting in significant reductions in morbidity and mortality through immune reconstitution and attenuation of homeostatic disruption. Importantly, restoration of immune function in PLWH with opportunistic infections occasionally leads to an intense and uncontrolled cytokine storm following ART initiation known as immune reconstitution inflammatory syndrome (IRIS). IRIS occurrence is associated with the severe and rapid clinical deterioration that results in significant morbidity and mortality. Here, we detail the determinants underlying IRIS development in PLWH, compiling the available knowledge in the field to highlight details of the inflammatory responses in IRIS associated with the most commonly reported opportunistic pathogens. This review also highlights gaps in the understanding of IRIS pathogenesis and summarizes therapeutic strategies that have been used for IRIS

In silico transcriptional analysis of mRNA and miRNA reveals unique biosignatures that characterizes different types of diabetes.

Diabetes (DM) has a significant impact on public health. We performed an in silico study of paired datasets of messenger RNA (mRNA) micro-RNA (miRNA) transcripts to delineate potential biosignatures that could distinguish prediabetes (pre-DM), type-1DM (T1DM) and type-2DM (T2DM). Two publicly available datasets containing expression values of mRNA and miRNA obtained from individuals diagnosed with pre-DM, T1DM or T2DM, and normoglycemic controls (NC), were analyzed using systems biology approaches to define combined signatures to distinguish different clinical groups. The mRNA profile of both pre-DM and T2DM was hallmarked by several differentially expressed genes (DEGs) compared to NC. Nevertheless, T1DM was characterized by an overall low number of DEGs. The miRNA signature profiles were composed of a substantially lower number of differentially expressed targets. Gene enrichment analysis revealed several inflammatory pathways in T2DM and fewer in pre-DM, but with shared findings such as Tuberculosis. The integration of mRNA and miRNA datasets improved the identification and discriminated the group composed by pre-DM and T2DM patients from that constituted by normoglycemic and T1DM individuals. The integrated transcriptomic analysis of mRNA and miRNA expression revealed a unique biosignature able to characterize different types of DM

Systems biology analysis of publicly available transcriptomic data reveals a critical link between AKR1B10 gene expression, smoking and occurrence of lung cancer.

BACKGROUND:Cigarette smoking is associated with an increased risk of developing respiratory diseases and various types of cancer. Early identification of such unfavorable outcomes in patients who smoke is critical for optimizing personalized medical care. METHODS:Here, we perform a comprehensive analysis using Systems Biology tools of publicly available data from a total of 6 transcriptomic studies, which examined different specimens of lung tissue and/or cells of smokers and nonsmokers to identify potential markers associated with lung cancer. RESULTS:Expression level of 22 genes was capable of classifying smokers from non-smokers. A machine learning algorithm revealed that AKR1B10 was the most informative gene among the 22 differentially expressed genes (DEGs) accounting for the classification of the clinical groups. AKR1B10 expression was higher in smokers compared to non-smokers in datasets examining small and large airway epithelia, but not in the data from a study of sorted alveolar macrophages. Moreover, AKR1B10 expression was relatively higher in lung cancer specimens compared to matched healthy tissue obtained from nonsmoking individuals. Although the overall accuracy of AKR1B10 expression level in distinction between cancer and healthy lung tissue was 76%, with a specificity of 98%, our results indicated that such marker exhibited low sensitivity, hampering its use for cancer screening such specific setting. CONCLUSION:The systematic analysis of transcriptomic studies performed here revealed a potential critical link between AKR1B10 expression, smoking and occurrence of lung cancer

Determinants of losses in the latent tuberculosis cascade of care in Brazil: A retrospective cohort study

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2020-04-07T17:24:59Z No. of bitstreams: 1 Araujo, N.C.N. Determinants....pdf: 1976039 bytes, checksum: ddf32d2f5cd1578d464d7953f3f141d4 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2020-04-07T18:03:57Z (GMT) No. of bitstreams: 1 Araujo, N.C.N. Determinants....pdf: 1976039 bytes, checksum: ddf32d2f5cd1578d464d7953f3f141d4 (MD5)Made available in DSpace on 2020-04-07T18:03:57Z (GMT). No. of bitstreams: 1 Araujo, N.C.N. Determinants....pdf: 1976039 bytes, checksum: ddf32d2f5cd1578d464d7953f3f141d4 (MD5) Previous issue date: 2020-01-17Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB). The funders had no role in study design, data extraction and analysis, the decision to publish, or the preparation of the manuscript.Escola Bahiana de Medicina e Saúde Pública. Salvador, Ba, Brasil / Fundação José Silveira. Instituto Brasileiro para Investigação da Tuberculose. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Salvador, BA, Brasil.Escola Bahiana de Medicina e Saúde Pública. Salvador, Ba, Brasil / Obras Sociais Irmã Dulce. Salvador, BA, Brasil.Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação José Silveira. Instituto Brasileiro para Investigação da Tuberculose. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Salvador, BA, Brasil.Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.Fundação José Silveira. Instituto Brasileiro para Investigação da Tuberculose. Salvador, BA, Brasil / / Universidade Federal da Bahia. Complexo Hospitalar Universitário Professor Edgard Santos. Salvador, BA, Brasil.Escola Bahiana de Medicina e Saúde Pública. Salvador, Ba, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities. Salvador, BA, Brasil.The present study evaluated factors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of tuberculosis (TB) patients, in a referral center from a highly endemic region in Brazil. Methods: Contacts of 1,672 TB patients were retrospectively studied between 2009 and 2014. Data on TB screening by clinical investigation, radiographic examination and tuberculin skin test (TST) were extracted from medical records. Losses in the cascade of care and TB incidence within 2-year follow-up were calculated. Results: From a total of 1,180 TB contacts initially identified, only 495 were examined (58% loss), and 20 were diagnosed with active TB at this stage. Furthermore, 435 persons returned for TST result interpretation and 351 (~81%) were TST positive. Among those with positive TST, 249 (73%) were treated with isoniazid for 6 months whereas 51 abandoned therapy early. Three individuals who did not receive LTBI treatment, one with incomplete treatment and another who completed treatment developed active TB. A logistic regression analysis revealed that increases in age were associated with losses in the LTBI cascade independent of other clinical and epidemiological characteristics. Conclusions: Major losses occur at initial stages and older patients are at higher risk of not completing the LTBI cascade of care

Molecular degree of perturbation of plasma inflammatory markers associated with tuberculosis reveals distinct disease profiles between Indian and Chinese populations

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-08-01T12:15:41Z No. of bitstreams: 1 Souza, D.O. Molecular degree of perturbation...2019.pdf: 1729409 bytes, checksum: ab65dea396416432df6627a7b3160e01 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-08-01T12:42:19Z (GMT) No. of bitstreams: 1 Souza, D.O. Molecular degree of perturbation...2019.pdf: 1729409 bytes, checksum: ab65dea396416432df6627a7b3160e01 (MD5)Made available in DSpace on 2019-08-01T12:42:19Z (GMT). No. of bitstreams: 1 Souza, D.O. Molecular degree of perturbation...2019.pdf: 1729409 bytes, checksum: ab65dea396416432df6627a7b3160e01 (MD5) Previous issue date: 2019-01-29Fundação Oswaldo Cruz, Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.Fundação Oswaldo Cruz, Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.Fundação Oswaldo Cruz, Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.National Institutes of Health- National Institute for Research in Tuberculosis. International Center for Excellence in Research. India.Fundação Oswaldo Cruz, Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.Henan Chest Hospital. Zhengzhou, China.Henan Chest Hospital. Zhengzhou, China.Henan Chest Hospital. Zhengzhou, China.Sino-US International Research Center for Tuberculosis, and Henan Public Health Center. Zhengzhou, China.Laboratory of Clinical Immunology and Microbiology. Bethesda, USA.Laboratory of Clinical Immunology and Microbiology. Bethesda, USA.Laboratory of Clinical Immunology and Microbiology. Bethesda, USA.Laboratory of Parasitic Diseases. Bethesda, USA.National Institutes of Health- National Institute for Research in Tuberculosis. International Center for Excellence in Research. India.Laboratory of Clinical Immunology and Microbiology. Bethesda, USA.University of São Paulo. School of Pharmaceutical Sciences. Department of Pathophysiology and Toxicology. São Paulo, SP, Brazil.Fundação Oswaldo Cruz, Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.Fundação Oswaldo Cruz, Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil / Vanderbilt University School of Medicine. Division of Infectious Diseases. Department of Medicine.Tuberculosis (TB) is a chronic inflammatory disease caused by Mycobacterium tuberculosis infection which causes tremendous morbidity and mortality worldwide. Clinical presentation of TB patients is very diverse and disease heterogeneity is associated with changes in biomarker signatures. Here, we compared at the molecular level the extent of individual inflammatory perturbation of plasma protein and lipid mediators associated with TB in patients in China versus India. We performed a cross-sectional study analyzing the overall degree of inflammatory perturbation in treatment-naïve pulmonary TB patients and uninfected individuals from India (TB: n = 97, healthy: n = 20) and China (TB: n = 100, healthy: n = 11). We employed the molecular degree of perturbation (MDP) adapted to plasma biomarkers to examine the overall changes in inflammation between these countries. M. tuberculosis infection caused a significant degree of molecular perturbation in patients from both countries, with higher perturbation detected in India. Interestingly, there were differences in biomarker perturbation patterns and the overall degree of inflammation. Patients with severe TB exhibited increased MDP values and Indian patients with this condition exhibited even higher degree of perturbation compared to Chinese patients. Network analyses identified IFN-α, IFN-β, IL-1RI and TNF-α as combined biomarkers that account for the overall molecular perturbation in the entire study population. Our results delineate the magnitude of the systemic inflammatory perturbation in pulmonary TB and reveal qualitative changes in inflammatory profiles between two countries with high disease prevalence

Polymorphisms in TLR4 and TNFA and Risk of Mycobacterium tuberculosis Infection and Development of Active Disease in Contacts of Tuberculosis Cases in Brazil: A Prospective Cohort Study

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-12-20T12:44:35Z No. of bitstreams: 1 Cubillos Angulo. J. Polymorphisms in TLR4 and TNFA...2018.pdf: 805310 bytes, checksum: bebe122765e604537a2614a12036daae (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-12-20T13:12:03Z (GMT) No. of bitstreams: 1 Cubillos Angulo. J. Polymorphisms in TLR4 and TNFA...2018.pdf: 805310 bytes, checksum: bebe122765e604537a2614a12036daae (MD5)Made available in DSpace on 2018-12-20T13:12:03Z (GMT). No. of bitstreams: 1 Cubillos Angulo. J. Polymorphisms in TLR4 and TNFA...2018.pdf: 805310 bytes, checksum: bebe122765e604537a2614a12036daae (MD5) Previous issue date: 2018This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Instituto Nacional de Ciência e Tecnologia (INCT, grant number: 573548/2008-0) and Fundação de Amparo à Pesquisa do Rio de Janeiro (FAPERJ, grant number: E-26/110.974/2011). AK is the recipient of a career award from CNPq (produtividade em pesquisa) and FAPERJ (Cientistas do Nosso Estado). The work from BBA and KFF was supported by intramural research program from FIOCRUZ and from the National Institutes of Health (U01AI115940). JMC-A was supported by the Organization of American States - Partnerships Program for Education and Training (OAS-PAEC). MBA receives a fellowship from the Fundação de Amparo à Pesquisa da Bahia (FAPESB).Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brazil / State University of North Fluminense Darcy Ribeiro. Recognize the Biology Laboratory. Center of Bioscience and Biotechnology. Rio de Janeiro, RJ, Brazil.Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brazil / Fundação Oswaldo Cruz. Instituto Osvaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brazil.Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, BrazilUniversidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Ribeirão Preto, SP, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brazil.Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, Tennessee, USA.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Vanderbilt University School of Medicine. Department of Medicine. Division of Infectious Diseases. Nashville, Tennessee, USA / University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Disease Research in Africa. Cape Town, South Africa / Universidade Salvador. Laureate University. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.Background: The role of genetic polymorphisms in latent tuberculosis (TB) infection and progression to active TB is not fully understood. Methods: We tested the single nucleotide polymorphisms (SNPs) rs5743708 (TLR2), rs4986791 (TLR4), rs361525 (TNFA), rs2430561 (IFNG) rs1143627 (IL1B) as risk factors for tuberculin skin test (TST) conversion or development of active TB in contacts of active TB cases. Contacts of microbiologically confirmed pulmonary TB cases were initially screened for longitudinal evaluation up to 24 months, with clinical examination and serial TST, between 1998 and 2004 at a referral center in Brazil. Data and biospecimens were collected from 526 individuals who were contacts of 177 active TB index cases. TST conversion was defined as ≥5 f TST result (0 mm) at baseline or month 4 visit. Independent associations were tested using logistic regression models

Polymorphisms in interferon pathway genes and risk of Mycobacterium tuberculosis infection in contacts of tuberculosis cases in Brazil

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2020-02-03T11:53:23Z No. of bitstreams: 1 Cubillos-Angulo JM Polymorphisms in Interferon Int J Infect Dis.pdf: 2351156 bytes, checksum: 46b584145c4ea7161f673f992685ac9c (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2020-02-03T12:21:55Z (GMT) No. of bitstreams: 1 Cubillos-Angulo JM Polymorphisms in Interferon Int J Infect Dis.pdf: 2351156 bytes, checksum: 46b584145c4ea7161f673f992685ac9c (MD5)Made available in DSpace on 2020-02-03T12:21:55Z (GMT). No. of bitstreams: 1 Cubillos-Angulo JM Polymorphisms in Interferon Int J Infect Dis.pdf: 2351156 bytes, checksum: 46b584145c4ea7161f673f992685ac9c (MD5) Previous issue date: 2019-01-13Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Instituto Nacional de Ciência e Tecnologia (INCT, Journal Pre-proof grant number: 421703/2017-2) and Fundação de Amparo à Pesquisa do Rio de Janeiro (FAPERJ, grant number: E-26/110.974/2011). BBA, JRLS, and AK are senior investigators from CNPq and AK and JRLS receive senior fellowships from FAPERJ. The work from BBA and KFF was supported by intramural research program from FIOCRUZ and from the National Institutes of Health (U01AI115940). JMC-A was supported by the Organization of American States - Partnerships Program for Education and Training (OAS-PAEC) and his study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) - Finance Code 001. MBA receives a fellowship from the Fundação de Amparo à Pesquisa da Bahia (FAPESB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil.Universidade Federal do Rio de Janeiro. Centro de Pesquisas em Doenças Infecciosas e Parasitárias. Laboratório de Micobacteriologia Molecular. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Pesquisas em Doenças Infecciosas e Parasitárias. Laboratório de Micobacteriologia Molecular. Rio de Janeiro, RJ, Brasil / Universidade Federal do Norte Fluminense Darcy Ribeiro. Centro de Biociências e Biotecnologia. Laboratório de Biologia do Reconhecer. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / Universidad Franz Tamayo. Coordinación Nacional de Investigación. La Paz, Bolivia.Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil.Vanderbilt University. School of Medicine. Nashville. Department of Medicine. Division of Infectious Diseases. Tennessee, USA.University of Washington. Department of Medicine. Seattle, WA, USA.Universidade Federal do Rio de Janeiro. Faculdade de Medicina e Complexo Hospitalar. Programa Acadêmico de Tuberculose. Rio de Janeiro, RJ, Brasil.University of Washington. Department of Medicine. Seattle, WA, USA.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Vanderbilt University. School of Medicine. Nashville. Department of Medicine. Division of Infectious Diseases. Tennessee, USA / University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Disease Research in Africa. Cape Town, South Africa / Universidade Salvador. Laureate Universities. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.Host genetic polymorphisms may be important in determining susceptibility to Mycobacterium tuberculosis (Mtb) infection, but their role is not fully understood. Detection of microbial DNA and activation of type I interferon (IFN) pathways regulate macrophage responses to Mtb infection. Methods: We examined whether seven candidate gene SNPs were associated with tuberculin skin test (TST) positivity in close contacts of microbiologically confirmed pulmonary TB patients in Brazil. Independent associations with TST positivity were tested using multivariable logistic regression (using genotypes and clinical variables) and genetic models. Results: Among 482 contacts of 145 TB index cases, 296 contacts were TST positive. Multivariable regression analysis adjusted for population admixture, age, family relatedness, sex and clinical variables related to increased TB risk demonstrated that SNPs in PYHIN1-IFI16-AIM2 rs1101998 (adjusted OR [aOR]: 3.72; 95%CI = 1.15–12.0; p=0.028) and in PYHIN1-IFI16-AIM2 rs1633256 (aOR= 24.84; 95%CI = 2.26–272.95; p=0.009) were associated with TST positivity in a recessive model. Furthermore, an IRF7 polymorphism (rs11246213) was associated with reduced odds of TST positivity in a dominant model (aOR: 0.50, 95%CI: 0.26-0.93; p=0.029). Conclusions: Polymorphisms in PYHIN1-IFI16-AIM2 rs1633256, rs1101998 and in IRF7 rs11246213 were associated with altered susceptibility to Mtb infection in this Brazilian cohort