title: IVIg immune reconstitution treatment alleviates the state of persistent immune activation and suppressed CD4 T cell counts in CVID.
abstract: Common variable immunodeficiency (CVID) is characterized by defective B cell function, impaired antibody production, and increased susceptibility to bacterial infections. Here, we addressed the hypothesis that poor antibody-mediated immune control of infections may result in substantial perturbations in the T cell compartment. Newly diagnosed CVID patients were sampled before, and 6-12 months after, initiation of intravenous immunoglobulin (IVIg) therapy. Treatment-naïve CVID patients displayed suppressed CD4 T cell counts and myeloid dendritic cell (mDC) levels, as well as high levels of immune activation in CD8 T cells, CD4 T cells, and invariant natural killer T (iNKT) cells. Expression of co-stimulatory receptors CD80 and CD83 was elevated in mDCs and correlated with T cell activation. Levels of both FoxP3+ T regulatory (Treg) cells and iNKT cells were low, whereas soluble CD14 (sCD14), indicative of monocyte activation, was elevated. Importantly, immune reconstitution treatment with IVIg partially restored the CD4 T cell and mDC compartments. Treatment furthermore reduced the levels of CD8 T cell activation and mDC activation, whereas levels of Treg cells and iNKT cells remained low. Thus, primary deficiency in humoral immunity with impaired control of microbial infections is associated with significant pathological changes in cell-mediated immunity. Furthermore, therapeutic enhancement of humoral immunity with IVIg infusions alleviates several of these defects, indicating a relationship between poor antibody-mediated immune control of infections and the occurrence of abnormalities in the T cell and mDC compartments. These findings help our understanding of the immunopathogenesis of primary immunodeficiency, as well as acquired immunodeficiency caused by HIV-1 infection.
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Dominic
authors.initials: D
authors.lastname: Paquin-Proulx
authors.forename: Bianca A N
authors.initials: BA
authors.lastname: Santos
authors.forename: Karina I
authors.initials: KI
authors.lastname: Carvalho
authors.forename: Myrthes
authors.initials: M
authors.lastname: Toledo-Barros
authors.forename: Ana Karolina
authors.initials: AK
authors.lastname: Barreto de Oliveira
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Kokron
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Markus
authors.initials: M
authors.lastname: Moll
authors.forename: Esper G
authors.initials: EG
authors.lastname: Kallas
authors.forename: Johan K
authors.initials: JK
authors.lastname: Sandberg
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D055815:Young Adult; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen