Humoral Dysregulation Associated with Increased Systemic Inflammation among Injection Heroin Users
| Autor: | Bo Zheng, James J. Kobie, Alexander F. Rosenberg, Brittany Carter, Michael S. Piepenbrink, William M Valenti, Atif Ali Khan, Catherine A. Bunce, Norman J. Haughey, Christopher F. Fucile, Sanjay B. Maggirwar, Memorie Samuel, Diane S. Morse, Juilee Thakar, Michael C. Keefer, Michelle Kiebala |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
B Cells HIV Infections Comorbidity HIV Antibodies Pathology and Laboratory Medicine Systemic inflammation Biochemistry 0302 clinical medicine Immunodeficiency Viruses Animal Cells Substance Abuse Intravenous lcsh:Science Immune Response education.field_of_study virus diseases 3. Good health Blood Medical Microbiology Viral Pathogens Physical Sciences Vaccination and immunization Cellular Types Antibody Immune Cells CD40 Ligand Immunology Microbiology 03 medical and health sciences Signs and Symptoms Alkaloids Recreational Drug Use Humans Antibody-Producing Cells education Microbial Pathogens B cell Pharmacology Preventive medicine Blood Cells Tumor Necrosis Factor-alpha lcsh:R Organisms Chemical Compounds Biology and Life Sciences Proteins medicine.disease Immunity Humoral Heroin Cross-Sectional Studies Public and occupational health 030104 developmental biology Humoral immunity lcsh:Q 030217 neurology & neurosurgery RNA viruses 0301 basic medicine Physiology lcsh:Medicine White Blood Cells Cocaine Immune Physiology Medicine and Health Sciences B-Lymphocytes Vaccines Immune System Proteins Multidisciplinary biology Hematology Hepatitis C Body Fluids Chemistry medicine.anatomical_structure Behavioral Pharmacology Viruses Female Pathogens Anatomy medicine.symptom Research Article medicine.drug Adult Narcotics Population New York Antibodies Blood Plasma Young Adult Immune system Diagnostic Medicine Virology Retroviruses mental disorders medicine Inflammation Hepatitis Viral vaccines business.industry Interleukin-8 Lentivirus HIV vaccines HIV Cell Biology Transforming Growth Factor alpha Immunoglobulin M Immunoglobulin G biology.protein business |
| Zdroj: | PLoS ONE, Vol 11, Iss 7, p e0158641 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Background Injection drug use is a growing major public health concern. Injection drug users (IDUs) have a higher incidence of co-morbidities including HIV, Hepatitis, and other infections. An effective humoral response is critical for optimal homeostasis and protection from infection; however, the impact of injection heroin use on humoral immunity is poorly understood. We hypothesized that IDUs have altered B cell and antibody profiles. Methods and Findings A comprehensive systems biology-based cross-sectional assessment of 130 peripheral blood B cell flow cytometry- and plasma- based features was performed on HIV-/Hepatitis C-, active heroin IDUs who participated in a syringe exchange program (n = 19) and healthy control subjects (n = 19). The IDU group had substantial polydrug use, with 89% reporting cocaine injection within the preceding month. IDUs exhibited a significant, 2-fold increase in total B cells compared to healthy subjects, which was associated with increased activated B cell subsets. Although plasma total IgG titers were similar between groups, IDUs had significantly higher IgG3 and IgG4, suggestive of chronic B cell activation. Total IgM was also increased in IDUs, as well as HIV Envelope-specific IgM, suggestive of increased HIV exposure. IDUs exhibited numerous features suggestive of systemic inflammation, including significantly increased plasma sCD40L, TNF-α, TGF-α, IL-8, and ceramide metabolites. Machine learning multivariate analysis distilled a set of 10 features that classified samples based on group with absolute accuracy. Conclusions These results demonstrate broad alterations in the steady-state humoral profile of IDUs that are associated with increased systemic inflammation. Such dysregulation may impact the ability of IDUs to generate optimal responses to vaccination and infection, or lead to increased risk for inflammation-related co-morbidities, and should be considered when developing immune-based interventions for this growing population. |
| Databáze: | OpenAIRE |
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