Simultaneous assessment of rotavirus-specific memory B cells and serological memory after B cell depletion therapy with rituximab
Rojas, Olga L.
Mantilla, Rubén D.
Franco, Manuel A.
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 pathogenspecific 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. © 2014 Herrera et al.
Cd27 Antigen ; Double Stranded Dna Antibody ; Monoclonal ; Immunoglobulin A ; Murine-Derived ; Immunoglobulin D ; Immunoglobulin G ; Immunoglobulin M ; Methylprednisolone ; Rheumatoid Factor ; Rituximab ; Tetanus Toxoid ; Autoantigen ; Immunoglobulin M ; Monoclonal Antibody ; Rituximab ; Aged ; Antibody Detection ; Antibody Titer ; Antigen Specificity ; Antiphospholipid Syndrome ; Autoimmune Disease ; Autoimmune Thrombocytopenia ; Clinical Article ; Controlled Study ; Enzyme Linked Immunosorbent Assay ; Flow Cytometry ; Human ; Human Cell ; Humoral Immune Deficiency ; Immunoglobulin Blood Level ; Kinetic Nephelometry ; Lupus Erythematosus Nephritis ; Male ; Memory Cell ; Nephelometry ; Nonhuman ; Plasma Cell ; Rheumatoid Arthritis ; Rotavirus ; Systemic Lupus Erythematosus ; B Lymphocyte ; Blood ; Drug Effects ; Immunological Memory ; Immunology ; Lymphocyte Depletion ; Procedures ; Rotavirus ; Species Difference ; Aged ; Antibodies ; Autoantigens ; B-Lymphocyte Subsets ; B-Lymphocytes ; Immunoglobulin M ; Immunologic Memory ; Lymphocyte Depletion ; Male ; Rotavirus ; Species Specificity ;
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