title: Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets.
abstract: BACKGROUND
  During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART).
  
  
  METHODS
  To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation.
  
  
  RESULTS
  Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups.
  
  
  CONCLUSIONS
  In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI.
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy; Department of Infectious and Tropical Diseases, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Pogliaghi
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy; Department of Infectious and Tropical Diseases, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ripa
authors.affiliation: Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Pensieroso
authors.affiliation: Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Tolazzi
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy; Department of Infectious and Tropical Diseases, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Chiappetta
authors.affiliation: Department of Infectious and Tropical Diseases, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Nozza
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy; Department of Infectious and Tropical Diseases, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.affiliation: Department of Infectious and Tropical Diseases, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tambussi
authors.affiliation: Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Scarlatti
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D015497:HIV-1; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007156:Immunologic Memory / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology; D013997:Time Factors
chemical_list: D044966:Anti-Retroviral Agents; D007072:Immunoglobulin D; D007075:Immunoglobulin M