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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Arthritis+Rheumatol
2014 ; 66
(9
): 2558-69
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Primary Sjögren s syndrome is characterized by distinct phenotypic and
transcriptional profiles of IgD+ unswitched memory B cells
#MMPMID24909310
Roberts ME
; Kaminski D
; Jenks SA
; Maguire C
; Ching K
; Burbelo PD
; Iadarola MJ
; Rosenberg A
; Coca A
; Anolik J
; Sanz I
Arthritis Rheumatol
2014[Sep]; 66
(9
): 2558-69
PMID24909310
show ga
OBJECTIVE: The significance of distinct B cell abnormalities in primary Sjögren's
syndrome (SS) remains to be established. We undertook this study to analyze the
phenotype and messenger RNA (mRNA) transcript profiles of B cell subsets in
patients with primary SS and to compare them with those in sicca syndrome
patients and healthy controls. METHODS: CD19+ B cells from 26 patients with
primary SS, 27 sicca syndrome patients, and 22 healthy controls were analyzed by
flow cytometry. Gene expression profiles of purified B cell subsets (from 3-5
subjects per group per test) were analyzed using Affymetrix gene arrays. RESULTS:
Patients with primary SS had lower frequencies of CD27+IgD- switched memory B
cells and CD27+IgD+ unswitched memory B cells compared with healthy controls.
Unswitched memory B cell frequencies were also lower in sicca syndrome patients
and correlated inversely with serologic hyperactivity in both disease states.
Further, unswitched memory B cells in primary SS had lower expression of CD1c and
CD21. Gene expression analysis of CD27+ memory B cells separated patients with
primary SS from healthy controls and identified a subgroup of sicca syndrome
patients with a primary SS-like transcript profile. Moreover, unswitched memory B
cell gene expression analysis identified 187 genes differentially expressed
between patients with primary SS and healthy controls. CONCLUSION: A decrease in
unswitched memory B cells with serologic hyperactivity is characteristic of both
established primary SS and a subgroup of sicca syndrome, which suggests the value
of these B cells both as biomarkers of future disease progression and for
understanding disease pathogenesis. Overall, the mRNA transcript analysis of
unswitched memory B cells suggests that their activation in primary SS takes
place through innate immune pathways in the context of attenuated
antigen-mediated adaptive signaling. Thus, our findings provide important insight
into the mechanisms and potential consequences of decreased unswitched memory B
cells in primary SS.