Class-switzched B cells display response to therapeutic B-cell depletion in rheumatoid arthritis

Möller, B; Aeberli, D; Eggli, S; Fuhrer, M; Vajtai, I; Vöglin, E; Ziswiler, HR; Dahinden, CA; Villiger, PM (2009). Class-switzched B cells display response to therapeutic B-cell depletion in rheumatoid arthritis. Arthritis research & therapy, 11(3), R62. London: BioMed Central 10.1186/ar2686

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Introduction Reconstitution of peripheral blood (PB) B cells after therapeutic depletion with the chimeric anti-CD20 antibody rituximab (RTX) mimics lymphatic ontogeny. In this situation, the repletion kinetics and migratory properties of distinct developmental B-cell stages and their correlation to disease activity might facilitate our understanding of innate and adaptive B-cell functions in rheumatoid arthritis (RA). Methods Thirty-five 'RTX-naïve' RA patients with active arthritis were treated after failure of tumour necrosis factor blockade in an open-label study with two infusions of 1,000 mg RTX. Prednisone dose was tapered according to clinical improvement from a median of 10 mg at baseline to 5 mg at 9 and 12 months. Conventional disease-modifying antirheumatic drugs were kept stable. Subsets of CD19+ B cells were assessed by flow cytometry according to their IgD and CD27 surface expression. Their absolute number and relative frequency in PB were followed every 3 months and were determined in parallel in synovial tissue (n = 3) or synovial fluid (n = 3) in the case of florid arthritis. Results Six of 35 patients fulfilled the European League Against Rheumatism criteria for moderate clinical response, and 19 others for good clinical response. All PB B-cell fractions decreased significantly in number (P < 0.001) after the first infusion. Disease activity developed independently of the total B-cell number. B-cell repopulation was dominated in quantity by CD27-IgD+ 'naïve' B cells. The low number of CD27+IgD- class-switched memory B cells (MemB) in the blood, together with sustained reduction of rheumatoid factor serum concentrations, correlated with good clinical response. Class-switched MemB were found accumulated in flaring joints. Conclusions The present data support the hypothesis that control of adaptive immune processes involving germinal centre-derived, antigen, and T-cell-dependently matured B cells is essential for successful RTX treatment.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery > Hand Surgery
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute for Immunology (discontinued)

UniBE Contributor:

Möller, Burkhard; Aeberli, Daniel; Eggli, Stefan; Vajtai, Istvan; Vögelin, Esther; Ziswiler, Hans Rudolf; Dahinden, Clemens A. and Villiger, Peter

ISSN:

1478-6354

Publisher:

BioMed Central

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:13

Last Modified:

08 Jun 2016 10:53

Publisher DOI:

10.1186/ar2686

PubMed ID:

19419560

Web of Science ID:

000269019300028

BORIS DOI:

10.7892/boris.32327

URI:

https://boris.unibe.ch/id/eprint/32327 (FactScience: 197415)

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