title: Reconstitution of the peripheral B lymphocyte compartment in patients with ANCA-associated vasculitides treated with rituximab for relapsing or refractory disease.
abstract: While in patients with rheumatoid arthritis B-cell repopulation starts within 9 months after rituximab (RTX) therapy, a delayed B-cell repopulation was reported in some RTX-treated patients with ANCA-associated vasculitides (AAV). To date, the frequency of AAV patients with impaired peripheral B-cell regeneration and the mechanisms leading to the constricted regenerative capacity are unknown. We analyzed the B-cell repopulation kinetic in 37 AAV patients treated with RTX followed by maintenance immunosuppressants. We report on serum concentrations of the B-cell-activating factor BAFF, immunoglobulins and B-cell subpopulations in patients that relapsed after RTX. B-cells were re-detectable in only one patient within 9 months after RTX. In 14 patients (41%), B-cell repopulation started later, after a mean observation time of 21 months. Only seven of these patients had detectable B-cells within the first year after RTX. Twenty patients (59%) had no B-cell reconstitution within the observation period. BAFF was increased in RTX-treated AAV patients compared to healthy controls and correlated inversely with peripheral B-cell numbers, IgG- and IgA concentrations. Immunoglobulin concentrations declined significantly after RTX and the IgG concentration correlated with B-cell numbers. Thirteen patients relapsed after RTX. Relapses occurred exclusively either after B-cell reconstitution had started or were accompanied by rising ANCA titres. In relapsed patients, the B-lymphocyte compartment consisted mainly of switched memory B-cells. Our data indicate that RTX treatment can induce secondary immunodeficiency in AAV, with hypogammaglobulinemia and long-lasting B-lymphopenia. Further studies are needed to define the pathophysiology of the impaired B-cell development in RTX-treated AAV patients.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg , Freiburg , Germany .
authors.forename: Nils
authors.initials: N
authors.lastname: Venhoff
authors.forename: Lena
authors.initials: L
authors.lastname: Niessen
authors.forename: Matthias
authors.initials: M
authors.lastname: Kreuzaler
authors.forename: Antonius G
authors.initials: AG
authors.lastname: Rolink
authors.forename: Fabian
authors.initials: F
authors.lastname: Hässler
authors.forename: Marta
authors.initials: M
authors.lastname: Rizzi
authors.forename: Reinhard E
authors.initials: RE
authors.lastname: Voll
authors.forename: Jens
authors.initials: J
authors.lastname: Thiel
mesh_terms: D000361:Agammaglobulinemia / Q000209:etiology / Q000276:immunology; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002452:Cell Count; D006801:Humans; D007156:Immunologic Memory; D008231:Lymphopenia / Q000209:etiology / Q000276:immunology; D012008:Recurrence; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D000069283:Rituximab
keywords: Antineutrophil cytoplasmic antibody; B lymphocytes; Wegener’s); granulomatosis with polyangiitis (GPA; rituximab