title: Older age is associated with peripheral blood expansion of naïve B cells in HIV-infected subjects on antiretroviral therapy.
abstract: Older HIV infected subjects were previously found to have significant B cell expansion during initial antiretroviral therapy in a prospective age-differentiated cohort of older and younger (≥45 vs. ≤30 years) HIV-infected subjects initiating antiretroviral therapy (ART) through the AIDS Clinical Trials Group. Here to further describe this expansion, using a subset of subjects from the same cohort, we characterized B cell phenotypes at baseline and after 192 weeks of ART in both older and younger HIV-infected groups and compared them to uninfected age-matched controls. We also examined whether phenotypes at baseline associated with response to tetanus and hepatitis A vaccine at 12 weeks. Forty six subjects were analyzed in the HIV infected group (21 older, 25 younger) and 30 in the control group (15 per age group). We observed naïve B cells to normalize in younger subjects after 192 weeks of ART, while in older subjects naïve B cells increased to greater levels than those of controls (p = 0.045). Absolute resting memory (RM) cell count was significantly lower in the older HIV infected group at baseline compared to controls and numbers normalized after 192 weeks of ART (p<0.001). Baseline RM cell count positively correlated with week 12 increase in antibody to tetanus vaccine among both younger and older HIV-infected subjects combined (p = 0.01), but not in controls. The age-associated naïve B cell expansion is a novel finding and we discuss several possible explanations for this observation. Relationship between RM cells at baseline and tetanus responses may lead to insights about the effects of HIV infection on B cell memory function and vaccine responses.
authors.affiliation: Geriatric Research Center Clinical Core (GRECC), Department of Infectious Diseases, Louis Stokes Cleveland VA Medical Center, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Puja
authors.initials: P
authors.lastname: Van Epps
authors.affiliation: Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Matining
authors.affiliation: Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Katherine
authors.initials: K
authors.lastname: Tassiopoulos
authors.affiliation: Geriatric Research Center Clinical Core (GRECC), Department of Infectious Diseases, Louis Stokes Cleveland VA Medical Center, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Donald D
authors.initials: DD
authors.lastname: Anthony
authors.affiliation: Department of Immunology and Microbiology, Rush Medical Center, Chicago, Illinois, United States of America.
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.affiliation: Department of Infectious Diseases, Metrohealth Medical Center, Cleveland, Ohio, United States of America, and Geriatric Research Center Clinical Core (GRECC), Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, United States of America.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kalayjian
authors.affiliation: Geriatric Research Center Clinical Core (GRECC), Department of Infectious Diseases, Louis Stokes Cleveland VA Medical Center, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: David H
authors.initials: DH
authors.lastname: Canaday
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000907:Antibodies, Bacterial / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology; D022362:Hepatitis A Vaccines / Q000008:administration & dosage; D006801:Humans; D007156:Immunologic Memory; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D013745:Tetanus Toxoid / Q000008:administration & dosage
chemical_list: D019380:Anti-HIV Agents; D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D022362:Hepatitis A Vaccines; D013745:Tetanus Toxoid