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Neuronal uptake of anti-Hu antibody, but not anti-Ri antibody, leads to cell death in brain slice cultures

Overview of attention for article published in Journal of Neuroinflammation, September 2014
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Title
Neuronal uptake of anti-Hu antibody, but not anti-Ri antibody, leads to cell death in brain slice cultures
Published in
Journal of Neuroinflammation, September 2014
DOI 10.1186/s12974-014-0160-0
Pubmed ID
Authors

John E Greenlee, Susan A Clawson, Kenneth E Hill, Blair Wood, Stacey L Clardy, Ikuo Tsunoda, Troy D Jaskowski, Noel G Carlson

Abstract

BackgroundAnti-Hu and anti-Ri antibodies are paraneoplastic immunoglobulin (Ig)G autoantibodies which recognize cytoplasmic and nuclear antigens present in all neurons. Although both antibodies produce similar immunohistological labeling, they recognize different neuronal proteins. Both antibodies are associated with syndromes of central nervous system dysfunction. However, the neurological deficits associated with anti-Hu antibody are associated with neuronal death and are usually irreversible, whereas neurological deficits in patients with anti-Ri antibody may diminish following tumor removal or immunosuppression.MethodsTo study the effect of anti-Hu and anti-Ri antibodies on neurons, we incubated rat hippocampal and cerebellar slice cultures with anti-Hu or anti-Ri sera from multiple patients. Cultures were evaluated in real time for neuronal antibody uptake and during prolonged incubation for neuronal death. To test the specificity of anti-Hu antibody cytotoxic effect, anti-Hu serum IgG was incubated with rat brain slice cultures prior to and after adsorption with its target Hu antigen, HuD.ResultsWe demonstrated that: 1) both anti-Hu and anti-Ri antibodies were rapidly taken up by neurons throughout both cerebellum and hippocampus; 2) antibody uptake occurred in living neurons and was not an artifact of antibody diffusion into dead cells; 3) intracellular binding of anti-Hu antibody produced neuronal cell death, whereas uptake of anti-Ri antibody did not affect cell viability during the period of study; and 4) adsorption of anti-Hu antisera against HuD greatly reduced intraneuronal IgG accumulation and abolished cytotoxicity, confirming specificity of antibody-mediated neuronal death.ConclusionsBoth anti-Hu and anti-Ri antibodies were readily taken up by viable neurons in slice cultures, but the two antibodies differed markedly in terms of their effects on neuronal viability. The ability of anti-Hu antibodies to cause neuronal death could account for the irreversible nature of paraneoplastic neurological deficits in patients with this antibody response. Our results raise questions as to whether anti-Ri antibody might initially induce reversible neuronal dysfunction, rather than causing cell death. The ability of IgG antibodies to access and react with intracellular neuronal proteins could have implications for other autoimmune diseases involving the central nervous system.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Chile 1 3%
United States 1 3%
Unknown 37 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 18%
Student > Doctoral Student 4 10%
Researcher 3 8%
Student > Master 3 8%
Professor 2 5%
Other 9 23%
Unknown 11 28%
Readers by discipline Count As %
Medicine and Dentistry 10 26%
Agricultural and Biological Sciences 4 10%
Neuroscience 4 10%
Biochemistry, Genetics and Molecular Biology 2 5%
Economics, Econometrics and Finance 1 3%
Other 3 8%
Unknown 15 38%
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 23 September 2014.
All research outputs
#20,237,640
of 22,764,165 outputs
Outputs from Journal of Neuroinflammation
#2,299
of 2,621 outputs
Outputs of similar age
#208,367
of 249,470 outputs
Outputs of similar age from Journal of Neuroinflammation
#25
of 33 outputs
Altmetric has tracked 22,764,165 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,621 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 249,470 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 33 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.