title: Immunity 12 years after alemtuzumab in RA: CD5⁺ B-cell depletion, thymus-dependent T-cell reconstitution and normal vaccine responses.
abstract: OBJECTIVE
  Lymphocyte depleting therapies have been used to treat refractory autoimmune disease, including RA, but treatment may be associated with long-term lymphopenia. It is unclear whether delayed reconstitution preferentially affects lymphocyte subsets, how this modulates immune challenges and whether thymic function influences the outcome. These questions are now addressed in a detailed analysis of RA patients 12 years after alemtuzumab (anti-CD52) treatment.
  
  
  METHODS
  Blood was obtained from 20 RA patients 12 years after alemtuzumab treatment. Lymphocyte subsets were enumerated by flow cytometry. T-cell receptor excision circles (TRECs)/ml were determined to quantify thymic function, and serological responses to neoantigens and recall antigens were assessed.
  
  
  RESULTS
  RA patients remained lymphopenic 12 years after their first dose of alemtuzumab. CD5(+) B cells, which may be associated with autoantibody production, were significantly reduced in alemtuzumab-treated patients compared with age-matched disease controls. In addition, naïve and memory CD4(+) T-cell subsets were present in altered proportions in patients who had received alemtuzumab, with increased effector memory CD4(+) T cells, and decreased naïve and central memory CD4(+) T cells. TRECs were detectable in alemtuzumab-treated patients and correlated with CD4(+) lymphocyte counts. Vaccine responses to neoantigens and recall antigens fell within the normal range for an ageing population.
  
  
  CONCLUSIONS
  Alemtuzumab therapy resulted in long-term alterations in lymphocyte subsets. The significance of these changes remains uncertain but patients respond normally to antigenic challenges. Thymic function remains an important determinant of T-cell reconstitution even several years after lymphocytotoxic therapy.
authors.affiliation: Institute of Cellular Medicine, Musculoskeletal Research Group, 4th Floor Catherine Cookson Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Anderson
authors.forename: Alice R
authors.initials: AR
authors.lastname: Lorenzi
authors.forename: Arthur
authors.initials: A
authors.lastname: Pratt
authors.forename: Tom
authors.initials: T
authors.lastname: Wooldridge
authors.forename: Julie
authors.initials: J
authors.lastname: Diboll
authors.forename: Catharien M U
authors.initials: CM
authors.lastname: Hilkens
authors.forename: John D
authors.initials: JD
authors.lastname: Isaacs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens / Q000276:immunology*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007109:Immunity / Q000502:physiology; D016130:Immunophenotyping; D007252:Influenza Vaccines / Q000008:administration & dosage; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018956:CD5 Antigens; D007252:Influenza Vaccines; D000074323:Alemtuzumab