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Multidimensional single cell based STAT phosphorylation profiling identifies a novel biosignature for evaluation of systemic lupus erythematosus activity.
- Source :
-
PloS one [PLoS One] 2011; Vol. 6 (7), pp. e21671. Date of Electronic Publication: 2011 Jul 22. - Publication Year :
- 2011
-
Abstract
- Introduction: Dysregulated cytokine action on immune cells plays an important role in the initiation and progress of systemic lupus erythematosus (SLE), a complex autoimmune disease. Comprehensively quantifying basal STATs phosphorylation and their signaling response to cytokines should help us to better understand the etiology of SLE.<br />Methods: Phospho-specific flow cytometry was used to measure the basal STAT signaling activation in three immune cell types of peripheral-blood mononuclear cells from 20 lupus patients, 9 rheumatoid arthritis (RA) patients and 13 healthy donors (HDs). A panel of 27 cytokines, including inflammatory cytokines, was measured with Bio-Plex™ Human Cytokine Assays. Serum Prolactin levels were measured with an immunoradiometric assay. STAT signaling responses to inflammatory cytokines (interferon α [IFNα], IFNγ, interleukin 2 [IL2], IL6, and IL10) were also monitored.<br />Results: We observed the basal activation of STAT3 in SLE T cells and monocytes, and the basal activation of STAT5 in SLE T cells and B cells. The SLE samples clustered into two main groups, which were associated with the SLE Disease Activity Index 2000, their erythrocyte sedimentation rate, and their hydroxychloroquine use. The phosphorylation of STAT5 in B cells was associated with cytokines IL2, granulocyte colony-stimulating factor (G-CSF), and IFNγ, whereas serum prolactin affected STAT5 activation in T cells. The responses of STAT1, STAT3, and STAT5 to IFNα were greatly reduced in SLE T cells, B cells, and monocytes, except for the STAT1 response to IFNα in monocytes. The response of STAT3 to IL6 was reduced in SLE T cells.<br />Conclusions: The basal activation of STATs signaling and reduced response to cytokines may be helpful us to identify the activity and severity of SLE.
- Subjects :
- Adult
B-Lymphocytes immunology
B-Lymphocytes metabolism
Biomarkers metabolism
Female
Humans
Interferon-alpha metabolism
Interleukin-6 metabolism
Lupus Erythematosus, Systemic blood
Lupus Erythematosus, Systemic immunology
Male
Phosphorylation
Prolactin blood
STAT5 Transcription Factor metabolism
Signal Transduction
T-Lymphocytes immunology
T-Lymphocytes metabolism
Flow Cytometry methods
Lupus Erythematosus, Systemic metabolism
Lupus Erythematosus, Systemic pathology
STAT Transcription Factors metabolism
Single-Cell Analysis methods
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 6
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 21799742
- Full Text :
- https://doi.org/10.1371/journal.pone.0021671