dc.contributor.author
Mahmood, Zafar
dc.contributor.author
Muhammad, Khalid
dc.contributor.author
Schmalzing, Marc
dc.contributor.author
Roll, Petra
dc.contributor.author
Dörner, Thomas
dc.contributor.author
Tony, Hans-Peter
dc.date.accessioned
2018-06-08T04:03:52Z
dc.date.available
2016-03-18T09:04:39.674Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/16501
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-20682
dc.description.abstract
Introduction Enhanced B cell activity, particularly memory B cells have gained
interest in evaluating response during therapies with biologics. CD27-IgD-
double-negative (DN) B cells lacking the conventional memory marker CD27 are
reported to be part of the memory compartment, however, only scarce data is
available for rheumatoid arthritis (RA). We therefore focused on DN B cells in
RA, studied their isotypes and modulation during interleukin-6 receptor (IL-
6R) inhibition by tocilizumab (TCZ). Methods DN B cells were phenotypically
analyzed from 40 RA patients during TCZ at baseline week 12, week 24 and 1
year. A single B cell polymerase chain reaction (PCR) approach was used to
study Ig receptors, VH gene rearrangements and specific isotypes. Results
Phenotypic analysis showed a significantly expanded population of DN B cells
in RA which contain a heterogeneous mixture of IgG-, IgA- and IgM-expressing
cells with a clear dominance of IgG+ cells. DN B cells carry rearranged heavy
chain gene sequences with a diversified mutational pattern consistent with
memory B cells. In contrast to tumor necrosis factor alpha (TNF-α) inhibition,
a significant reduction in mutational frequency of BCR gene rearrangements at
week 12, 24 and 1 year (P <0.0001) was observed by in vivo IL-6R inhibition.
These changes were observed for all BCR isotypes IgG, IgA and IgM at week 12,
24 and 1 year (P <0.0001). IgA-RF, IgA serum level and IgA+ DN B cells
decreased significantly (P <0.05) at week 12 and week 24 during TCZ. Patients
with a good European League Against Rheumatism (EULAR) response to TCZ had
less DN B cells at baseline as compared to moderate responders (P = 0.006).
Univariate logistic regression analysis revealed that the frequency of DN B
cells at baseline is inversely correlated to a subsequent good EULAR response
(P = 0.024) with an odds ratio of 1.48 (95% confidence interval as 1.05 to
2.06). Conclusions In RA, the heterogeneous DN B cell compartment is expanded
and dominated by IgG isotype. TCZ can modulate the mutational status of DN Ig
isotype receptors over 1 year. Interestingly, the frequency of DN B cells in
RA may serve as a baseline predictor of subsequent EULAR response to TCZ
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
CD27-IgD- memory B cells are modulated by in vivo interleukin-6 receptor (IL-
6R) blockade in rheumatoid arthritis
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Arthritis Research & Therapy. - 17 (2015), Artikel Nr. 61
dcterms.bibliographicCitation.doi
10.1186/s13075-015-0580-y
dcterms.bibliographicCitation.url
http://arthritis-research.biomedcentral.com/articles/10.1186/s13075-015-0580-y
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000024185
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000006126
dcterms.accessRights.openaire
open access