-
1دورية أكاديمية
المؤلفون: Ladomersky, Erik, Zhai, Lijie, Lauing, Kristen L, Bell, April, Xu, Jiahui, Kocherginsky, Masha, Zhang, Bin, Wu, Jennifer D, Podojil, Joseph R, Platanias, Leonidas C, Mochizuki, Aaron Y, Prins, Robert M, Kumthekar, Priya, Raizer, Jeffrey J, Dixit, Karan, Lukas, Rimas V, Horbinski, Craig, Wei, Min, Zhou, Changyou, Pawelec, Graham, Campisi, Judith, Grohmann, Ursula, Prendergast, George C, Munn, David H, Wainwright, Derek A
المصدر: Clinical Cancer Research. 26(19)
مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Brain Cancer, Neurosciences, Clinical Research, Rare Diseases, Orphan Drug, Aging, Cancer, Brain Disorders, Immunotherapy, Adult, Age Factors, Aged, Aged, 80 and over, Animals, B7-H1 Antigen, Brain, CTLA-4 Antigen, Cellular Senescence, Disease Models, Animal, Female, Glioblastoma, Humans, Immune Checkpoint Inhibitors, Immunosuppression Therapy, Indoleamine-Pyrrole 2, 3, -Dioxygenase, Isocitrate Dehydrogenase, Male, Mice, Knockout, Middle Aged, Progression-Free Survival, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
الوصف: PurposeWild-type isocitrate dehydrogenase-expressing glioblastoma (GBM) is the most common and aggressive primary brain tumor with a median age at diagnosis of ≥65 years. It accounts for approximately 90% of all GBMs and has a median overall survival (OS) of
وصف الملف: application/pdf
-
2دورية أكاديمية
المؤلفون: Johnson, Douglas B, Bordeaux, Jennifer, Kim, Ju Young, Vaupel, Christine, Rimm, David L, Ho, Thai H, Joseph, Richard W, Daud, Adil I, Conry, Robert M, Gaughan, Elizabeth M, Hernandez-Aya, Leonel F, Dimou, Anastasios, Funchain, Pauline, Smithy, James, Witte, John S, McKee, Svetlana B, Ko, Jennifer, Wrangle, John M, Dabbas, Bashar, Tangri, Shabnam, Lameh, Jelveh, Hall, Jeffrey, Markowitz, Joseph, Balko, Justin M, Dakappagari, Naveen
المصدر: Clinical cancer research : an official journal of the American Association for Cancer Research. 24(21)
مصطلحات موضوعية: Cell Line, Tumor, Humans, Melanoma, Neoplasm Metastasis, HLA-DR Antigens, Biopsy, Neoplasm Staging, Prognosis, Treatment Outcome, Retreatment, Immunohistochemistry, Protein Binding, Models, Biological, Adult, Aged, Middle Aged, Female, Male, Indoleamine-Pyrrole 2, 3, -Dioxygenase, Programmed Cell Death 1 Receptor, Biomarkers, Tumor, Antineoplastic Agents, Immunological, B7-H1 Antigen, Cancer, Prevention, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Oncology and Carcinogenesis, Oncology & Carcinogenesis
الوصف: Purpose: PD-1/L1 axis-directed therapies produce clinical responses in a subset of patients; therefore, biomarkers of response are needed. We hypothesized that quantifying key immunosuppression mechanisms within the tumor microenvironment by multiparameter algorithms would identify strong predictors of anti-PD-1 response.Experimental Design: Pretreatment tumor biopsies from 166 patients treated with anti-PD-1 across 10 academic cancer centers were fluorescently stained with multiple markers in discovery (n = 24) and validation (n = 142) cohorts. Biomarker-positive cells and their colocalization were spatially profiled in pathologist-selected tumor regions using novel Automated Quantitative Analysis algorithms. Selected biomarker signatures, PD-1/PD-L1 interaction score, and IDO-1/HLA-DR coexpression were evaluated for anti-PD-1 treatment outcomes.Results: In the discovery cohort, PD-1/PD-L1 interaction score and/or IDO-1/HLA-DR coexpression was strongly associated with anti-PD-1 response (P = 0.0005). In contrast, individual biomarkers (PD-1, PD-L1, IDO-1, HLA-DR) were not associated with response or survival. This finding was replicated in an independent validation cohort: patients with high PD-1/PD-L1 and/or IDO-1/HLA-DR were more likely to respond (P = 0.0096). These patients also experienced significantly improved progression-free survival (HR = 0.36; P = 0.0004) and overall survival (HR = 0.39; P = 0.0011). In the combined cohort, 80% of patients exhibiting higher levels of PD-1/PD-L1 interaction scores and IDO-1/HLA-DR responded to PD-1 blockers (P = 0.000004). In contrast, PD-L1 expression was not predictive of survival.Conclusions: Quantitative spatial profiling of key tumor-immune suppression pathways by novel digital pathology algorithms could help more reliably select melanoma patients for PD-1 monotherapy. Clin Cancer Res; 24(21); 5250-60. ©2018 AACR.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/92k1g956Test
-
3دورية أكاديمية
المصدر: Stem cells translational medicine. 6(1)
مصطلحات موضوعية: T-Lymphocytes, Monocytes, Spheroids, Cellular, Mesenchymal Stem Cells, Animals, Swine, Humans, Heparin, Anti-Inflammatory Agents, Immunosuppression, Cell Culture Techniques, Lymphocyte Activation, Cell Proliferation, Solubility, Indoleamine-Pyrrole 2, 3, -Dioxygenase, Interferon-gamma, Cell-Derived Microparticles, Immunomodulation, Cellular, Indoleamine 2, 3-dioxygenase, Mesenchymal stromal cells, Spheroids, Indoleamine-Pyrrole 2, 3, -Dioxygenase, Indoleamine 2, 3-dioxygenase, Clinical Research, Regenerative Medicine, Stem Cell Research, Transplantation, 5.2 Cellular and gene therapies, Inflammatory and Immune System, Biochemistry and Cell Biology, Medical Biotechnology, Clinical Sciences
الوصف: The immunomodulatory activity of mesenchymal stem/stromal cells (MSCs) to suppress innate and adaptive immune responses offers a potent cell therapy for modulating inflammation and promoting tissue regeneration. However, the inflammatory cytokine milieu plays a critical role in stimulating MSC immunomodulatory activity. In particular, interferon-γ (IFN-γ)-induced expression of indoleamine 2,3-dioxygenase (IDO) is primarily responsible for MSC suppression of T-cell proliferation and activation. Although pretreatment with IFN-γ is commonly used to prime MSCs for immunomodulatory activity prior to transplantation, the transient effects of pretreatment may limit the potential of MSCs to potently modulate immune responses. Therefore, the objective of this study was to investigate whether microparticle-mediated presentation of bioactive IFN-γ within three-dimensional spheroidal MSC aggregates could precisely regulate and induce sustained immunomodulatory activity. Delivery of IFN-γ via heparin-microparticles within MSC aggregates induced sustained IDO expression during 1 week of culture, whereas IDO expression by IFN-γ-pretreated MSC spheroids rapidly decreased during 2 days. Furthermore, sustained IDO expression induced by IFN-γ-loaded microparticles resulted in an increased and sustained suppression of T-cell activation and proliferation in MSC cocultures with CD3/CD28-activated peripheral blood mononuclear cells. The increased suppression of T cells by MSC spheroids containing IFN-γ-loaded microparticles was dependent on induction of IDO and supported by affecting monocyte secretion from pro- to anti-inflammatory cytokines. Altogether, microparticle delivery of IFN-γ within MSC spheroids provides a potent means of enhancing and sustaining immunomodulatory activity to control MSC immunomodulation after transplantation and thereby improve the efficacy of MSC-based therapies aimed at treating inflammatory and immune diseases. Stem Cells Translational Medicine 2017;6:223-237.
الوصول الحر: https://escholarship.org/uc/item/94v837nnTest
-
4دورية أكاديمية
المؤلفون: Müller, Sören, Agnihotri, Sameer, Shoger, Karsen E, Myers, Max I, Smith, Nicholas, Chaparala, Srilakshmi, Villanueva, Clarence R, Chattopadhyay, Ansuman, Lee, Adrian V, Butterfield, Lisa H, Diaz, Aaron, Okada, Hideho, Pollack, Ian F, Kohanbash, Gary
المصدر: JCI Insight. 3(7)
مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Immunization, Immunotherapy, Vaccine Related, Biotechnology, Clinical Research, Rare Diseases, Brain Cancer, Pediatric, Cancer, Clinical Trials and Supportive Activities, Neurosciences, Minority Health, Brain Disorders, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Adolescent, Adult, B7-H1 Antigen, Biomarkers, Tumor, Brain Neoplasms, Cancer Vaccines, Carboxymethylcellulose Sodium, Child, Follow-Up Studies, Glioma, Humans, Immunogenicity, Vaccine, Indoleamine-Pyrrole 2, 3, -Dioxygenase, Lymphocyte Activation, Male, Monocytes, Poly I-C, Polylysine, Progression-Free Survival, Sequence Analysis, RNA, Survival Analysis, T-Lymphocytes, Vaccines, Subunit, Young Adult, Cancer immunotherapy, Cellular immune response, Peptides, Vaccines, Biomedical and clinical sciences, Health sciences
الوصف: Low-grade gliomas (LGGs) are the most common brain tumor affecting children. We recently reported an early phase clinical trial of a peptide-based vaccine, which elicited consistent antigen-specific T cell responses in pediatric LGG patients. Additionally, we observed radiologic responses of stable disease (SD), partial response (PR), and near-complete/complete response (CR) following therapy. To identify biomarkers of clinical response in peripheral blood, we performed RNA sequencing on PBMC samples collected at multiple time points. Patients who showed CR demonstrated elevated levels of T cell activation markers, accompanied by a cytotoxic T cell response shortly after treatment initiation. At week 34, patients with CR demonstrated both IFN signaling and Poly-IC:LC adjuvant response patterns. Patients with PR demonstrated a unique, late monocyte response signature. Interestingly, HLA-V expression, before or during therapy, and an early monocytic hematopoietic response were strongly associated with SD. Finally, low IDO1 and PD-L1 expression before treatment and early elevated levels of T cell activation markers were associated with prolonged progression-free survival. Overall, our data support the presence of unique peripheral immune patterns in LGG patients associated with different radiographic responses to our peptide vaccine immunotherapy. Future clinical trials, including our ongoing phase II LGG vaccine immunotherapy, should monitor these response patterns.
وصف الملف: application/pdf
-
5دورية أكاديمية
المؤلفون: Monjazeb, Arta M, Kent, Michael S, Grossenbacher, Steven K, Mall, Christine, Zamora, Anthony E, Mirsoian, Annie, Chen, Mingyi, Kol, Amir, Shiao, Stephen L, Reddy, Abhinav, Perks, Julian R, Culp, William TN, Sparger, Ellen E, Canter, Robert J, Sckisel, Gail D, Murphy, William J
المصدر: Clinical Cancer Research. 22(17)
مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Immunization, Vaccine Related, Clinical Trials and Supportive Activities, Cancer, Biotechnology, Clinical Research, Animals, Disease Models, Animal, Dogs, Enzyme Activation, Female, Immunomodulation, Immunosuppression Therapy, Indoleamine-Pyrrole 2, 3, -Dioxygenase, Melanoma, Experimental, Mice, Neoplasms, Oligodeoxyribonucleotides, Radioimmunotherapy, T-Lymphocyte Subsets, Treatment Outcome, Tumor Microenvironment, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
الوصف: PurposePrevious studies demonstrate that intratumoral CpG immunotherapy in combination with radiotherapy acts as an in-situ vaccine inducing antitumor immune responses capable of eradicating systemic disease. Unfortunately, most patients fail to respond. We hypothesized that immunotherapy can paradoxically upregulate immunosuppressive pathways, a phenomenon we term "rebound immune suppression," limiting clinical responses. We further hypothesized that the immunosuppressive enzyme indolamine-2,3-dioxygenase (IDO) is a mechanism of rebound immune suppression and that IDO blockade would improve immunotherapy efficacy.Experimental designWe examined the efficacy and immunologic effects of a novel triple therapy consisting of local radiotherapy, intratumoral CpG, and systemic IDO blockade in murine models and a pilot canine clinical trial.ResultsIn murine models, we observed marked increase in intratumoral IDO expression after treatment with radiotherapy, CpG, or other immunotherapies. The addition of IDO blockade to radiotherapy + CpG decreased IDO activity, reduced tumor growth, and reduced immunosuppressive factors, such as regulatory T cells in the tumor microenvironment. This triple combination induced systemic antitumor effects, decreasing metastases, and improving survival in a CD8(+) T-cell-dependent manner. We evaluated this novel triple therapy in a canine clinical trial, because spontaneous canine malignancies closely reflect human cancer. Mirroring our mouse studies, the therapy was well tolerated, reduced intratumoral immunosuppression, and induced robust systemic antitumor effects.ConclusionsThese results suggest that IDO maintains immune suppression in the tumor after therapy, and IDO blockade promotes a local antitumor immune response with systemic consequences. The efficacy and limited toxicity of this strategy are attractive for clinical translation. Clin Cancer Res; 22(17); 4328-40. ©2016 AACR.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/0jw8r8xxTest
-
6دورية أكاديمية
المؤلفون: Lee, Sulggi A, Mefford, Joel A, Huang, Yong, Witte, John S, Martin, Jeffrey N, Haas, David W, Mclaren, Paul J, Mushiroda, Taisei, Kubo, Michiaki, Byakwaga, Helen, Hunt, Peter W, Kroetz, Deanna L
المصدر: AIDS. 30(11)
مصطلحات موضوعية: Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Human Genome, Clinical Research, Genetics, Sexually Transmitted Infections, HIV/AIDS, Infectious Diseases, Aetiology, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Adult, Anti-Retroviral Agents, Female, HIV Infections, Humans, Indoleamine-Pyrrole 2, 3, -Dioxygenase, Interferon-gamma, Kynurenine, Male, Metabolism, Plasma, Risk Assessment, Signal Transduction, Survival Analysis, Toll-Like Receptors, Tryptophan, Tumor Necrosis Factor-alpha, Uganda, antiretroviral therapy, genome-wide association study, HIV, kynurenine, tryptophan, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology, Biomedical and clinical sciences, Health sciences
الوصف: ObjectivePlasma kynurenine/tryptophan ratio, a biomarker of indoleamine 2,3-dioxygenase-1 (IDO) activity, is a strong independent predictor of mortality in HIV-infected Ugandans initiating antiretroviral therapy (ART) and may play a key role in HIV pathogenesis. We performed a genome-wide study to identify potential host genetic determinants of kynurenine/tryptophan ratio in HIV-infected ART-suppressed Ugandans.Design/methodsWe performed genome-wide and exome array genotyping and measured plasma kynurenine/tryptophan ratio during the initial 6-12 months of suppressive ART in Ugandans. We evaluated more than 16 million single nucleotide polymorphisms in association with log10 kynurenine/tryptophan ratio using linear mixed models adjusted for cohort, sex, pregnancy, and ancestry.ResultsAmong 597 Ugandans, 62% were woman, median age was 35, median baseline CD4 cell count was 135 cells/μl, and median baseline HIV-1 RNA was 5.1 log10 copies/ml. Several polymorphisms in candidate genes TNF, IFNGR1, and TLR4 were associated with log10 kynurenine/tryptophan ratio (P
وصف الملف: application/pdf
-
7دورية أكاديمية
المؤلفون: Avelino-Silva, Vivian I, Miyaji, Karina T, Hunt, Peter W, Huang, Yong, Simoes, Marisol, Lima, Sheila B, Freire, Marcos S, Caiaffa-Filho, Helio H, Hong, Marisa A, Costa, Dayane Alves, Dias, Juliana Zanatta C, Cerqueira, Natalia B, Nishiya, Anna Shoko, Sabino, Ester Cerdeira, Sartori, Ana M, Kallas, Esper G
المصدر: PLOS Neglected Tropical Diseases. 10(12)
مصطلحات موضوعية: Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Vaccine Related, Vaccine Related (AIDS), Minority Health, Emerging Infectious Diseases, Prevention, Sexually Transmitted Infections, Biotechnology, Women's Health, HIV/AIDS, Clinical Research, Immunization, Health Disparities, Infection, Good Health and Well Being, Adult, Antibodies, Neutralizing, Antibodies, Viral, CD4-CD8 Ratio, Female, HIV Infections, Humans, Immunogenicity, Vaccine, Indoleamine-Pyrrole 2, 3, -Dioxygenase, Kynurenine, Male, Middle Aged, Prospective Studies, Tryptophan, Viremia, Yellow Fever, Yellow Fever Vaccine, Yellow fever virus, Biological Sciences, Medical and Health Sciences, Tropical Medicine, Biological sciences, Biomedical and clinical sciences, Health sciences
الوصف: BackgroundHIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence vaccine response in this population.MethodsWe prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models.Results12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV-infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers.ConclusionsHIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio.
وصف الملف: application/pdf
-
8دورية أكاديمية
المؤلفون: Somsouk, Ma, Estes, Jacob D, Deleage, Claire, Dunham, Richard M, Albright, Rebecca, Inadomi, John M, Martin, Jeffrey N, Deeks, Steven G, McCune, Joseph M, Hunt, Peter W
المصدر: AIDS. 29(1)
مصطلحات موضوعية: Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Clinical Research, HIV/AIDS, Sexually Transmitted Infections, 2.1 Biological and endogenous factors, Aetiology, Infection, Adult, Antiretroviral Therapy, Highly Active, Apoptosis, CD4-Positive T-Lymphocytes, Cell Proliferation, Chronic Disease, Cross-Sectional Studies, Epithelial Cells, Female, HIV Infections, HIV-1, Humans, Indoleamine-Pyrrole 2, 3, -Dioxygenase, Inflammation, Interleukin-6, Intestinal Mucosa, Lipopolysaccharide Receptors, Male, Middle Aged, Neutrophil Infiltration, epithelial proliferation, HIV, immune activation, inflammation, microbial translocation, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology, Biomedical and clinical sciences, Health sciences
الوصف: ObjectiveMicrobial translocation and innate immune action characterize HIV infection. Continued gut mucosal dysfunction during treatment and its relationship to CD4 T-cell recovery has not been well described.DesignA cross-sectional study was performed of antiretroviral therapy (ART)-suppressed (immunologic responders with CD4 > 500 cells/μl and immunologic nonresponders with CD4
وصف الملف: application/pdf
-
9دورية أكاديمية
المؤلفون: Martinez, Priscilla, Tsai, Alexander C, Muzoora, Conrad, Kembabazi, Annet, Weiser, Sheri D, Huang, Yong, Haberer, Jessica E, Martin, Jeffrey N, Bangsberg, David R, Hunt, Peter W
المصدر: JAIDS Journal of Acquired Immune Deficiency Syndromes. 65(4)
مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Mental Illness, HIV/AIDS, Clinical Research, Infectious Diseases, Depression, Mental Health, Sexually Transmitted Infections, Behavioral and Social Science, Brain Disorders, Adult, Antiretroviral Therapy, Highly Active, Female, HIV Infections, Humans, Indoleamine-Pyrrole 2, 3, -Dioxygenase, Kynurenine, Male, Metabolic Networks and Pathways, Plasma, Treatment Outcome, Tryptophan, Uganda, tryptophan catabolism, indoleamine 2, 3-dioxygenase-1, depression, antiretroviral therapy, Sub-Saharan Africa, Public Health and Health Services, Virology, Clinical sciences, Epidemiology, Public health
الوصف: BackgroundMajor depressive disorder is highly prevalent among HIV-infected persons, and depression symptom severity improves during the course of HIV antiretroviral therapy (ART). The potential biologic pathways explaining these phenomena remain unclear. We investigated the extent to which ART-mediated suppression of the kynurenine pathway of tryptophan catabolism (via indoleamine 2,3-dioxygenase-1 and potentially other sources) may correlate with improvements in depression symptom severity in this setting.MethodWe used the first year of data from the Uganda AIDS Rural Treatment Outcomes Study, a prospective cohort of 504 HIV-infected individuals initiating their first ART regimen in rural Uganda. We fitted random-effects regression models to estimate the associations between plasma tryptophan, plasma kynurenine, dietary diversity, and self-reported depression symptom severity.ResultsGreater depressive symptoms were associated with both lower plasma tryptophan and higher plasma kynurenine/tryptophan (KT) ratio over 12-month follow-up. In multivariable-adjusted models, declines in KT ratio and increases in plasma tryptophan levels partially explained ART-mediated improvements in depressive symptom severity. The association between KT ratio and depression symptom severity was stronger among persons with protein-deficient diets than among those with protein-rich diets.ConclusionsIndoleamine 2,3-dioxygenase-1-mediated tryptophan catabolism may contribute to depression symptom severity among HIV-infected individuals, particularly among those with poor dietary protein intake. ART-mediated improvements in depressive symptom severity may also be at least partially mediated by immunologic mechanisms. Interventions to reduce immune activation, and dietary protein supplementation, may be promising strategies to further reduce depression in this setting.
وصف الملف: application/pdf
-
10دورية أكاديمية
المؤلفون: Baer, Stephanie L, Colombo, Rhonda E, Johnson, Maribeth H, Wakade, Sushama, Pacholczyk, Gabriela, Newman-Whitlow, Cheryl, Thompson, Stuart A, Saag, Michael S, Martin, Jeffrey N, Floris-Moore, Michelle, Huang, Lei, Mellor, Andrew L
المصدر: Journal of Investigative Medicine, vol 69, iss 6
مصطلحات موضوعية: Biomedical and Clinical Sciences, Immunology, Infectious Diseases, HIV/AIDS, Clinical Research, Aging, Infection, Bacterial Translocation, Case-Control Studies, Cohort Studies, HIV Infections, Humans, Indoleamine-Pyrrole 2, Dioxygenase, Lipopolysaccharides, Neopterin, immune tolerance, inflammation, Clinical Sciences, General Clinical Medicine
الوقت: 1238 - 1244, 3
الوصف: Immune activation complicates HIV despite antiretroviral therapy (ART). Indoleamine 2,3 dioxygenase (IDO) catabolizes tryptophan (T) to kynurenine (K), regulating immune activity, and IDO activity increases with age. This study examines the relationship of IDO activity, bacterial translocation, and aging in people living with HIV (PLWH) on ART. Samples and data from PLWH on ART from the Centers for AIDS Research Network of Integrated Clinical Systems and from matched HIV-uninfected patients (controls) from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study were analyzed. The ratio of K to T (K:T) and neopterin were indicators of inflammation; 16S ribosomal DNA (16S rDNA) and lipopolysaccharide (LPS) were markers of bacterial translocation. Samples and data from 205 PLWH and 99 controls were analyzed. PLWH had higher K:T values across all ages, with a significant relationship between age and K:T for both groups. CD4 count or CD4 nadir had no association with K:T. There was no positive association between level of 16S rDNA or LPS detection and K:T. K:T and neopterin were associated. PLWH had elevated IDO activity, at younger ages, despite ART. This study suggests K:T ratio increases with age in both groups and is elevated in PLWH at all ages compared with age-matched controls.
وصف الملف: application/pdf
العلاقة: qt3k12v18g; https://escholarship.org/uc/item/3k12v18gTest
