title: Immune reconstitution 20 years after treatment with alemtuzumab in a rheumatoid arthritis cohort: implications for lymphocyte depleting therapies.
abstract: Alemtuzumab, an anti-CD52 monoclonal antibody, was administered to patients with RA between 1991 and 1994. We have followed a cohort of recipients since that time and previously reported significant delays in immune reconstitution. Here we report >20 years of follow-up data from this unique cohort.
  
  
  
  Surviving alemtuzumab recipients were age, sex and disease duration matched with RA controls. Updated mortality and morbidity data were collected for alemtuzumab recipients. For both groups antigenic responses were assessed following influenza, Pneumovax II and combined diphtheria/tetanus/poliovirus vaccines. Circulating cytokines and lymphocyte subsets were also quantified.
  
  
  
  Of 16 surviving alemtuzumab recipients, 13 were recruited: 9 recipients underwent a full clinical assessment and 4 had case notes review only. Since our last review 10 patients had died from causes of death consistent with long-standing RA, and no suggestion of compromised immune function. Compared with controls the alemtuzumab cohort had significantly reduced CD4+and CD8+central memory T-cells, CD5+B cells, naïve B cells and CD19+CD24hiCD38hitransitional (putative regulatory) B cells. Nonetheless vaccine responses were comparable between groups. There were significantly higher serum IL-15 and IFN-γ levels in the alemtuzumab cohort. IL-15 levels were inversely associated with CD4+total memory and central memory T cells.
  
  
  
  After 20 years the immune system of alemtuzumab recipients continues to show differences from disease controls. Nonetheless mortality and morbidity data, alongside vaccination responses, do not suggest clinical immune compromise. As lymphodepleting therapies, including alemtuzumab, continue to be administered this work is important with regard to long-term immune monitoring and stages of immune recovery.
authors.affiliation: Institute of Cellular Medicine, Newcastle University and National Institute for Health Research Newcastle Biomedical Research Centre at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Faye A H
authors.initials: FA
authors.lastname: Cooles
authors.affiliation: Institute of Cellular Medicine, Newcastle University and National Institute for Health Research Newcastle Biomedical Research Centre at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Anderson
authors.affiliation: Addenbrooke's NHS trust, Cambridge, UK.
authors.forename: Tracey
authors.initials: T
authors.lastname: Drayton
authors.affiliation: Institute of Cellular Medicine, Newcastle University and National Institute for Health Research Newcastle Biomedical Research Centre at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Harry
authors.affiliation: Institute of Cellular Medicine, Newcastle University and National Institute for Health Research Newcastle Biomedical Research Centre at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Diboll
authors.affiliation: Institute of Cellular Medicine, Newcastle University and National Institute for Health Research Newcastle Biomedical Research Centre at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Lee
authors.initials: L
authors.lastname: Munro
authors.affiliation: Institute of Cellular Medicine, Newcastle University and National Institute for Health Research Newcastle Biomedical Research Centre at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Nishanthi
authors.initials: N
authors.lastname: Thalayasingham
authors.affiliation: Addenbrooke's NHS trust, Cambridge, UK.
authors.forename: Andrew J K
authors.initials: AJ
authors.lastname: Östör
authors.affiliation: Institute of Cellular Medicine, Newcastle University and National Institute for Health Research Newcastle Biomedical Research Centre at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK. john.isaacs@newcastle.ac.uk.
authors.forename: John D
authors.initials: JD
authors.lastname: Isaacs
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D008212:Lymphocyte Depletion / Q000379:methods; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D000074323:Alemtuzumab
keywords: Alemtuzumab; CD5+ B cells; Immune homeostasis; Lymphodepletion; Rheumatoid arthritis