title: Humoral Dysregulation Associated with Increased Systemic Inflammation among Injection Heroin Users.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Infectious Diseases Division, Department of Medicine, University of Rochester, Rochester, NY, United States of America.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Piepenbrink
authors.affiliation: School of Medicine, Howard University, Washington, DC, United States of America.
authors.forename: Memorie
authors.initials: M
authors.lastname: Samuel
authors.affiliation: Infectious Diseases Division, Department of Medicine, University of Rochester, Rochester, NY, United States of America.
authors.forename: Bo
authors.initials: B
authors.lastname: Zheng
authors.affiliation: School of Medicine, Texas A&M University, Bryan, TX, United States of America.
authors.forename: Brittany
authors.initials: B
authors.lastname: Carter
authors.affiliation: Division of Allergy, Immunology, and Rheumatology, Department of Medicine, University of Rochester, Rochester, NY, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Fucile
authors.affiliation: Infectious Diseases Division, Department of Medicine, University of Rochester, Rochester, NY, United States of America.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bunce
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, NY, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kiebala
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, NY, United States of America.
authors.forename: Atif A
authors.initials: AA
authors.lastname: Khan
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, NY, United States of America.
authors.forename: Juilee
authors.initials: J
authors.lastname: Thakar
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, NY, United States of America.
authors.forename: Sanjay B
authors.initials: SB
authors.lastname: Maggirwar
authors.affiliation: Departments of Psychiatry and Medicine, University of Rochester, Rochester, NY, United States of America.
authors.forename: Diane
authors.initials: D
authors.lastname: Morse
authors.affiliation: Division of Allergy, Immunology, and Rheumatology, Department of Medicine, University of Rochester, Rochester, NY, United States of America.
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Rosenberg
authors.affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD, United States of America.
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Haughey
authors.affiliation: Infectious Diseases Division, Department of Medicine, University of Rochester, Rochester, NY, United States of America.|Trillium Health, Rochester, NY, United States of America.
authors.forename: William
authors.initials: W
authors.lastname: Valenti
authors.affiliation: Infectious Diseases Division, Department of Medicine, University of Rochester, Rochester, NY, United States of America.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.affiliation: Infectious Diseases Division, Department of Medicine, University of Rochester, Rochester, NY, United States of America.
authors.forename: James J
authors.initials: JJ
authors.lastname: Kobie
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000097:blood / Q000276:immunology; D015897:Comorbidity; D003430:Cross-Sectional Studies; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000453:epidemiology / Q000276:immunology; D006526:Hepatitis C / Q000097:blood / Q000453:epidemiology / Q000276:immunology; D003932:Heroin / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D016209:Interleukin-8 / Q000097:blood / Q000276:immunology; D008297:Male; D009294:Narcotics / Q000008:administration & dosage / Q000276:immunology; D009518:New York / Q000453:epidemiology; D015819:Substance Abuse, Intravenous / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D016211:Transforming Growth Factor alpha / Q000097:blood / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology; D055815:Young Adult
chemical_list: D015483:HIV Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016209:Interleukin-8; D009294:Narcotics; D016211:Transforming Growth Factor alpha; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D003932:Heroin