Toggle Main Menu Toggle Search

ePrints

Immune reconstitution 20 years after treatment with alemtuzumab in a rheumatoid arthritis cohort: implications for lymphocyte depleting therapies

Lookup NU author(s): Dr Faye Cooles, Dr Amy Anderson, Dr Rachel Harry, Julie Diboll, Lee Munro, Dr Nishanthi Thalayasingham, Professor John Isaacs

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Background: 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.Method: 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.Results: 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, naive B cells and CD19(+) CD24(hi)CD38(hi) transitional (putative regulatory) B cells. Nonetheless vaccine responses were comparable between groups. There were significantly higher serum IL-15 and IFN-gamma levels in the alemtuzumab cohort. IL-15 levels were inversely associated with CD4(+) total memory and central memory T cells.Conclusion: 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.


Publication metadata

Author(s): Cooles FAH, Anderson AE, Drayton T, Harry RA, Diboll J, Munro L, Thalayasingham N, Ostor AJK, Isaacs JD

Publication type: Article

Publication status: Published

Journal: Arthritis Research & Therapy

Year: 2016

Volume: 18

Online publication date: 20/12/2016

Acceptance date: 21/11/2016

ISSN (electronic): 1478-6362

Publisher: BioMed Central Ltd.

URL: http://dx.doi.org/10.1186/s13075-016-1188-6

DOI: 10.1186/s13075-016-1188-6


Altmetrics

Altmetrics provided by Altmetric


Actions

    Link to this publication


Share