Short- and long-term effects of anti-CD20 treatment on B cell ontogeny in bone marrow of patients with rheumatoid arthritis.
BACKGROUND
In the present study we evaluated changes in the B cell phenotype in peripheral blood and bone marrow (BM) of patients with rheumatoid arthritis (RA) following anti-CD20 treatment using rituximab.


METHODS
Blood and BM samples were obtained from 37 patients with RA prior to rituximab treatment. Ten of these patients were resampled 1 month following rituximab, 14 patients after 3 months and the remaining 13 patients were included in the long-term follow up. B cell populations were characterized by CD27/IgD/CD38/CD24 expression.


RESULTS
One and three months following rituximab BM retained up to 30% of B cells while circulation was totally depleted of B cells. Analysis of the remaining BM B cells showed prevalence of immature and/or transitional B cells (CD38++CD24++) and CD27+IgD- memory cells, while IgD+ cells were completely depleted. A significant reduction of CD27+ cells in BM and in circulation was observed long after rituximab treatment (mean 22 months), while levels of naive B cells in BM and in circulation were increased. The levels of rheumatoid factor decline after rituximab treatment but returned to baseline levels at the time of retreatment.


CONCLUSIONS
Anti-CD20 treatment achieves a depletion of IgD+ B cells shortly after the treatment. At the long term follow up, a reduction of CD27+ B cells was observed in blood and BM. The prolonged inability to up-regulate CD27 may inhibit the renewal of memory B cells. This reduction of CD27+ B cells does not prevent autoantibody production suggesting that mechanisms regulating the formation of auto reactive clones are not disrupted by rituximab.
Rehnberg
Maria
M
Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Guldhedsgatan 10A, Gothenburg, Sweden. maria.rehnberg@rheuma.gu.se
Amu
Sylvie
S
Tarkowski
Andrej
A
Bokarewa
Maria I
MI
Brisslert
Mikael
M
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD / Q000096:biosynthesis; D018951:Antigens, CD20 / Q000276:immunology / Q000378:metabolism; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D000069283:Rituximab; D013995:Time; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D018951:Antigens, CD20; D018501:Antirheumatic Agents; D007072:Immunoglobulin D; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000069283:Rituximab
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