title: Simultaneous assessment of rotavirus-specific memory B cells and serological memory after B cell depletion therapy with rituximab.
abstract: The mechanisms that contribute to the maintenance of serological memory are still unclear. Rotavirus (RV) memory B cells (mBc) are enriched in IgM(+) and CD27- subpopulations, which are associated with autoimmune diseases pathogenesis. In patients with autoimmune diseases treated with Rituximab (RTX), some autoantibodies (auto-Abs) decrease after treatment, but other auto-Abs and pathogen-specific IgG Abs remain unchanged. Thus, maintenance of autoimmune and pathogen-specific serological memory may depend on the type of antigen and/or Ab isotype evaluated. Antigen-specific mBc and antigen-specific Abs of different isotypes have not been simultaneously assessed in patients after RTX treatment. To study the relationship between mBc subpopulations and serological memory we characterized total, RV- and tetanus toxoid (TT)-specific mBc by flow cytometry in patients with autoimmune diseases before and after treatment with RTX. We also measured total, RV- and TT-Abs, and some auto-Abs by kinetic nephelometry, ELISA, and EliA tests, respectively. Minor differences were observed between the relative frequencies of RV-mBc in healthy controls and patients with autoimmune disease. After RTX treatment, naïve Bc and total, RV- and TT-specific mBc [IgM(+), switched (IgA(+)/IgG(+)), IgM(+) only, IgD(+) only, and CD27- (IgA(+)/IgG(+)/IgM(+))] were significantly diminished. An important decrease in total plasma IgM and minor decreases in total IgG and IgA levels were also observed. IgM rheumatoid factor, IgG anti-CCP, and IgG anti-dsDNA were significantly diminished. In contrast, RV-IgA, RV-IgG and RV-IgG1, and TT-IgG titers remained stable. In conclusion, in patients with autoimmunity, serological memory against RV and TT seem to be maintained by long-lived plasma cells, unaffected by RTX, and an important proportion of total IgM and serological memory against some auto-antigens seem to be maintained by short-lived plasma cells, dependent on mBc precursors depleted by RTX.
authors.affiliation: Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Herrera
authors.affiliation: Unidad de Inmunología, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.
authors.forename: Olga L
authors.initials: OL
authors.lastname: Rojas
authors.affiliation: Riesgo de Fractura S.A. - CAYRE I.P.S, Bogotá, Colombia.
authors.forename: Carolina
authors.initials: C
authors.lastname: Duarte-Rey
authors.affiliation: Riesgo de Fractura S.A. - CAYRE I.P.S, Bogotá, Colombia.
authors.forename: Rubén D
authors.initials: RD
authors.lastname: Mantilla
authors.affiliation: Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Juana
authors.initials: J
authors.lastname: Angel
authors.affiliation: Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Franco
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D001324:Autoantigens / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D007156:Immunologic Memory / Q000187:drug effects*; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D012401:Rotavirus / Q000276:immunology*; D013045:Species Specificity
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001324:Autoantigens; D007075:Immunoglobulin M; D000069283:Rituximab