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Rheumatology (Oxford). 2012 Aug;51(8):1397-406. doi: 10.1093/rheumatology/kes038. Epub 2012 Mar 24.

Immunity 12 years after alemtuzumab in RA: CD5⁺ B-cell depletion, thymus-dependent T-cell reconstitution and normal vaccine responses.

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1
Institute of Cellular Medicine, Musculoskeletal Research Group, 4th Floor Catherine Cookson Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.

Abstract

OBJECTIVES:

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.

PMID:
22447884
DOI:
10.1093/rheumatology/kes038
[Indexed for MEDLINE]
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