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Immunoregulatory soluble CTLA-4 modifies effector T-cell responses in systemic lupus erythematosus

Overview of attention for article published in Arthritis Research & Therapy, August 2016
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Title
Immunoregulatory soluble CTLA-4 modifies effector T-cell responses in systemic lupus erythematosus
Published in
Arthritis Research & Therapy, August 2016
DOI 10.1186/s13075-016-1075-1
Pubmed ID
Authors

Lekh N. Dahal, Neil Basu, Hazem Youssef, Rahul C. Khanolkar, Robert N. Barker, Lars P. Erwig, Frank J. Ward

Abstract

The inhibitory CTLA-4 molecule is a crucial regulator of immune responses and a target for therapeutic intervention in both autoimmunity and cancer. In particular, CTLA-4 is important in controlling antigen-specific immunity, including responses to autoantigens associated with autoimmune disease. Here, we investigate cytokine responses to a range of lupus-associated autoantigens and assess whether the alternatively spliced isoform of CTLA-4, soluble CTLA-4 (sCTLA-4), contributes to immune regulation of autoantigen-specific immunity in systemic lupus erythematosus (SLE). The cell culture supernatant production of sCTLA-4 as well as the cytokines IL-10, IFN-γ, and IL-17 from peripheral blood mononuclear cells (PBMC) from lupus patients and age- and sex-matched healthy volunteer donors were measured in response to previously identified histone and small nuclear ribonucleoprotein (snRNP) autoantigen-derived peptides (H391-105, H471-93, and U170K131-151) by ELISA. We also examined the functional contribution of sCTLA-4 to immune regulation in the context of these autoantigenic peptides following blockade of sCTLA-4 with a selective anti-sCTLA-4 monoclonal antibody, JMW-3B3. We identified responses to autoantigenic peptides, which revealed qualitative differences in cytokine (IL-10, IL-17, and IFN-γ) profiles between SLE patients and healthy donors. PBMC from healthy donors responded to each of the lupus peptides by secreting IFN-γ and IL-17, but PBMC from SLE patients produced IL-10. Although we did not observe differences in the levels of serum or PBMC culture supernatant sCTLA-4 in either cohort, blockade of sCTLA-4 in PBMC cultures responding to antigen enhanced the cytokine profiles associated with each group. The results show that lupus autoantigen-derived peptides display varied immunogenicity in lupus versus healthy volunteer donors, while sCTLA-4 acts to regulate the T-cell activity independently of response profile.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 49 100%

Demographic breakdown

Readers by professional status Count As %
Student > Doctoral Student 8 16%
Student > Bachelor 8 16%
Student > Ph. D. Student 8 16%
Researcher 4 8%
Student > Postgraduate 3 6%
Other 6 12%
Unknown 12 24%
Readers by discipline Count As %
Immunology and Microbiology 11 22%
Medicine and Dentistry 10 20%
Biochemistry, Genetics and Molecular Biology 6 12%
Agricultural and Biological Sciences 4 8%
Chemical Engineering 1 2%
Other 4 8%
Unknown 13 27%
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 10 August 2016.
All research outputs
#20,655,488
of 25,371,288 outputs
Outputs from Arthritis Research & Therapy
#2,907
of 3,380 outputs
Outputs of similar age
#300,401
of 381,893 outputs
Outputs of similar age from Arthritis Research & Therapy
#40
of 50 outputs
Altmetric has tracked 25,371,288 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 3,380 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one is in the 7th percentile – i.e., 7% of its peers scored the same or lower than it.
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