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Transcriptome Analysis of Peripheral Blood in Chronic Inflammatory Demyelinating Polyradiculoneuropathy Patients Identifies TNFR1 and TLR Pathways in the IVIg Response

Overview of attention for article published in Medicine (Wolters Kluwer), May 2016
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Title
Transcriptome Analysis of Peripheral Blood in Chronic Inflammatory Demyelinating Polyradiculoneuropathy Patients Identifies TNFR1 and TLR Pathways in the IVIg Response
Published in
Medicine (Wolters Kluwer), May 2016
DOI 10.1097/md.0000000000003370
Pubmed ID
Authors

Alexandra Richard, Jean-Christophe Corvol, Rabab Debs, Pauline Reach, Khadija Tahiri, Wassila Carpentier, Justine Gueguen, Vincent Guillemot, Céline Labeyrie, David Adams, Karine Viala, Fleur Cohen Aubart

Abstract

We have studied the response to intravenous immunoglobulins (IVIg) by a transcriptomic approach in 11 chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients (CIDP duration = 6 [0.83-6.5] years). RNA was extracted from cells in whole blood collected before and 3 weeks after IVIg treatment, and hybridized on Illumina chips. After RNA quality controls, gene expression was analyzed using statistical tests fitted for microarrays (R software, limma package), and a pathway analysis was performed using DAVID software. We identified 52 genes with expression that varied significantly after IVIg (fold change [FC] > 1.2, P < 0.001, false discovery rate [FDR] <0.05). Among these 52 genes, 7 were related to immunity, 3 were related to the tumor necrosis factor (TNF)-α receptor 1 (TNFR1) pathway (inhibitor of caspase-activated DNase (ICAD): FC = 1.8, P = 1.7E-7, FDR = 0.004; p21 protein-activated kinase 2 [PAK2]: FC = 1.66, P = 2.6E-5, FDR = 0.03; TNF-α-induced protein 8-like protein 1 [TNFAIP8L1]: P = 1.00E-05, FDR = 0.026), and 2 were related to Toll-like receptors (TLRs), especially TLRs 7 and 9, and were implicated in autoimmunity. These genes were UNC93B1 (FC = 1.6, P = 2E-5, FDR = 0.03), which transports TLRs 7 and 9 to the endolysosomes, and RNF216 (FC = 1.5, P = 1E-05, FDR = 0.03), which promotes TLR 9 degradation. Pathway analysis showed that the TNFR1 pathway was significantly lessened by IVIg (enrichment score = 24, Fischer exact test = 0.003). TNF-α gene expression was higher in responder patients than in nonresponders; however, it decreased after IVIg in responders (P = 0.04), but remained stable in nonresponders. Our data suggest the actions of IVIg on the TNFR1 pathway and an original mechanism involving innate immunity through TLRs in CIDP pathophysiology and the response to IVIg. We conclude that responder patients have stronger inflammatory activity that is lessened by IVIg.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 2%
Unknown 40 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 17%
Student > Master 7 17%
Student > Ph. D. Student 6 15%
Student > Bachelor 3 7%
Student > Doctoral Student 3 7%
Other 6 15%
Unknown 9 22%
Readers by discipline Count As %
Medicine and Dentistry 15 37%
Neuroscience 3 7%
Agricultural and Biological Sciences 3 7%
Biochemistry, Genetics and Molecular Biology 2 5%
Nursing and Health Professions 2 5%
Other 1 2%
Unknown 15 37%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 May 2016.
All research outputs
#20,657,128
of 25,374,917 outputs
Outputs from Medicine (Wolters Kluwer)
#9,624
of 16,345 outputs
Outputs of similar age
#245,823
of 327,276 outputs
Outputs of similar age from Medicine (Wolters Kluwer)
#312
of 469 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
So far Altmetric has tracked 16,345 research outputs from this source. They receive a mean Attention Score of 4.7. This one is in the 24th percentile – i.e., 24% of its peers scored the same or lower than it.
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