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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
(12
): 3404-12
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Disease activity in systemic lupus erythematosus correlates with expression of
the transcription factor AT-rich-interactive domain 3A
#MMPMID25185498
Ward JM
; Rose K
; Montgomery C
; Adrianto I
; James JA
; Merrill JT
; Webb CF
Arthritis Rheumatol
2014[Dec]; 66
(12
): 3404-12
PMID25185498
show ga
OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex and multifactorial
autoimmune disease with striking clinical, immunologic, and genetic
heterogeneity, despite nearly ubiquitous antinuclear antibody (ANA) production.
Multiple gene polymorphisms have been associated with the disease, but these
individually account for only a very small percentage of overall SLE risk. In
earlier studies, constitutive expression of the DNA-binding protein
AT-rich-interactive domain 3A (ARID3a) in transgenic mouse B lymphocyte lineage
cells led to spontaneous ANA production and preferential development of B cells
associated with production of polyreactive antibodies. Therefore, we undertook
this study to determine whether ARID3a was overexpressed in B lymphocytes of SLE
patients and whether ARID3a expression was associated with disease severity.
METHODS: A cross-section of SLE patients, rheumatoid arthritis patients, and age-
and sex-matched controls was analyzed longitudinally for lupus disease activity,
numbers of ARID3a+ peripheral blood mononuclear B cells from multiple B cell
subsets, and immunoglobulin and cytokine levels. RESULTS: Fifty of 115 SLE
patients (43%) had dramatically increased numbers of ARID3a+ B cells compared to
healthy controls. ARID3a was not expressed in naive B cells of healthy controls,
but was abundant in these precursors of antibody-secreting cells in SLE patients.
Total numbers of ARID3a+ B cells correlated with increased disease activity as
defined by SLE Disease Activity Index scores in individuals assessed at 3 time
points. CONCLUSION: These findings identify B cell anomalies in SLE that allow
stratification of patient samples based on ARID3a expression and implicate ARID3a
as a potential marker of CD19+ B lymphocytes correlated with disease activity.