Reconstitution of the Peripheral B Lymphocyte Compartment in Patients With ANCA-associated Vasculitides Treated With Rituximab for Relapsing or Refractory Disease

Autoimmunity. 2014 Sep;47(6):401-8. doi: 10.3109/08916934.2014.914174. Epub 2014 May 6.

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.

Keywords: Antineutrophil cytoplasmic antibody; B lymphocytes; Wegener’s); granulomatosis with polyangiitis (GPA; rituximab.

MeSH terms

  • Agammaglobulinemia / etiology
  • Agammaglobulinemia / immunology
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / immunology*
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / physiopathology
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / therapy*
  • Antibodies, Monoclonal, Murine-Derived* / adverse effects
  • Antibodies, Monoclonal, Murine-Derived* / therapeutic use
  • Antirheumatic Agents* / adverse effects
  • Antirheumatic Agents* / therapeutic use
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Cell Count
  • Humans
  • Immunologic Memory
  • Lymphopenia / etiology
  • Lymphopenia / immunology
  • Recurrence
  • Rituximab

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Rituximab