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

• Published in: Rheumatology (Oxford, England) Vol. 51; no. 8; pp. 1397 - 1406
• Main Authors: ANDERSON, Amy E, LORENZI, Alice R, PRATT, Arthur, WOOLDRIDGE, Tom, DIBOLL, Julie, HILKENS, Catharien M. U, ISAACS, John D
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.08.2012
• Subjects: Adult; Aged; Aged, 80 and over; Alemtuzumab; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents - therapeutic use; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; B-Lymphocytes - immunology; Biological and medical sciences; Case-Control Studies; CD5 Antigens - immunology; Cohort Studies; Diseases of the osteoarticular system; Female; Flow Cytometry; Follow-Up Studies; Humans; Immunity - physiology; Immunomodulators; Immunophenotyping; Inflammatory joint diseases; Influenza Vaccines - administration & dosage; Lymphocyte Count; Lymphocyte Depletion; Lymphopenia - drug therapy; Lymphopenia - etiology; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; T-Lymphocytes - immunology; Thymus Gland - immunology; Antineoplastic agent; Immunopathology; Thymus gland; CD5+ B cells; Diseases of the osteoarticular system; Rheumatology; Autoimmune disease; immune reconstitution; Inflammatory joint disease; B-Lymphocyte; Alemtuzumab; Immunity; Immunomodulator; Prevention; vaccine responses; Immunoprophylaxis; Chronic; Immunological investigation; Rheumatoid arthritis; T-Lymphocyte; β Cell; Immunosuppressive agent; thymic function
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/kes038

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. 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. 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. 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.