title: Alterations of self-reactive antibody repertoires in HIV disease: an insight into the role of T cells in the selection of autoreactive B cells.
abstract: Infection with human immunodeficiency virus (HIV) is characterized by a progressive depletion of CD4(+) T cells that parallels a dysfunction of the B cell compartment and a disturbed recognition of self-antigens. The relationship between T lymphocyte homeostasis and abnormalities in the selection of self-reactive B cells is not clear as yet. We have therefore compared repertoires of natural antibodies of healthy donors and of patients at various stages of HIV infection. The reactivity of IgM and IgG antibodies in plasma of healthy blood donors and of HIV-positive patients with high and low CD4(+) T cell counts was assessed by semi-quantitative immunoblotting using self-antigens extracted from normal human tissues. Repertoires of reactivites were compared between groups of individuals by means of multiparametric statistical analysis. We observed that repertoires of self-reactive IgM and IgG from HIV-seropositive patients exhibited significantly altered patterns of reactivity, as compared to those of healthy controls. Further, self-reactive repertoires of IgM and IgG of patients with high CD4(+) T cell counts differed significantly from those of patients with low CD4(+) T cell counts. A longitudinal analysis of self-reactive antibody repertoires of progressor and non-progressor patients suggested an influence of CD4(+) T cell counts on immunoglobulin reactivity toward self-antigens. These observations support the hypothesis that altered T cell/B cell interactions due to altered CD4(+) T cell help severely impact on the selection of self-reactive antibody repertoires and may contribute to the onset of pathological autoimmunity in HIV disease.
authors.affiliation: INSERM U430 and Université Pierre et Marie Curie, Institut des Cordeliers, Paris, France. stahld@uni-muenster.de
authors.forename: Dorothea
authors.initials: D
authors.lastname: Stahl
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
authors.forename: Namita
authors.initials: N
authors.lastname: Misra
authors.forename: Marina
authors.initials: M
authors.lastname: Karmochkine
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Walter
authors.initials: W
authors.lastname: Sibrowski
authors.forename: Michel D
authors.initials: MD
authors.lastname: Kazatchkine
mesh_terms: D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D018791:CD4 Lymphocyte Count; D002450:Cell Communication / Q000276:immunology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology; D006679:HIV Seropositivity / Q000097:blood / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D013270:Stomach / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M