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Autoantibodies in breast cancer sera are not epiphenomena and may participate in carcinogenesis

Overview of attention for article published in BMC Cancer, May 2015
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Title
Autoantibodies in breast cancer sera are not epiphenomena and may participate in carcinogenesis
Published in
BMC Cancer, May 2015
DOI 10.1186/s12885-015-1385-8
Pubmed ID
Authors

Félix Fernández Madrid, Marie-Claire Maroun, Ofelia A Olivero, Michael Long, Azadeh Stark, Lawrence I Grossman, Walter Binder, Jingsheng Dong, Matthew Burke, S David Nathanson, Richard Zarbo, Dhananjay Chitale, Rocío Zeballos-Chávez, Carol Peebles

Abstract

The objective of this work was to demonstrate that autoantibodies in breast cancer sera are not epiphenomena, and exhibit unique immunologic features resembling the rheumatic autoimmune diseases. We performed a comprehensive study of autoantibodies on a collection of sera from women with breast cancer or benign breast disease, undergoing annual screening mammography. All women in this study had suspicious mammography assessment and underwent a breast biopsy. We used indirect immunofluorescence, the crithidia assay for anti-dsDNA antibodies, and multiple ELISAs for extractable nuclear antigens. Autoantibodies were detected in virtually all patients with breast cancer, predominantly of the IgG1 and IgG3 isotypes. The profile detected in breast cancer sera showed distinctive features, such as antibodies targeting mitochondria, centrosomes, centromeres, nucleoli, cytoskeleton, and multiple nuclear dots. The majority of sera showing anti-mitochondrial antibodies did not react with the M2 component of pyruvate dehydrogenase, characteristic of primary biliary cirrhosis. Anti-centromere antibodies were mainly anti-CENP-B. ELISAs for extractable nuclear antigens and the assays for dsDNA were negative. The distinctive autoantibody profile detected in BC sera is the expression of tumor immunogenicity. Although some of these features resemble those in the rheumatic autoimmune diseases and primary biliary cirrhosis, the data suggest the involvement of an entirely different set of epithelial antigens in breast cancer. High titer autoantibodies targeting centrosomes, centromeres, and mitochondria were detected in a small group of healthy women with suspicious mammography assessment and no cancer by biopsy; this suggests that the process triggering autoantibody formation starts in the pre-malignant phase and that future studies using validated autoantibody panels may allow detection of breast cancer risk in asymptomatic women. Autoantibodies developing in breast cancer are not epiphenomena, but likely reflect an antigen-driven autoimmune response triggered by epitopes developing in the mammary gland during breast carcinogenesis. Our results support the validity of the multiple studies reporting association of autoantibodies with breast cancer. Results further suggest significant promise for the development of panels of breast cancer-specific, premalignant-phase autoantibodies, as well as studies on the autoantibody response to tumor associated antigens in the pathogenesis of cancer.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 48 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 19%
Student > Bachelor 6 13%
Student > Master 6 13%
Researcher 5 10%
Other 4 8%
Other 8 17%
Unknown 10 21%
Readers by discipline Count As %
Medicine and Dentistry 15 31%
Agricultural and Biological Sciences 8 17%
Biochemistry, Genetics and Molecular Biology 6 13%
Computer Science 2 4%
Sports and Recreations 2 4%
Other 3 6%
Unknown 12 25%
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 02 March 2016.
All research outputs
#15,331,767
of 22,803,211 outputs
Outputs from BMC Cancer
#4,106
of 8,297 outputs
Outputs of similar age
#156,437
of 264,753 outputs
Outputs of similar age from BMC Cancer
#116
of 223 outputs
Altmetric has tracked 22,803,211 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,297 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 40th percentile – i.e., 40% of its peers scored the same or lower than it.
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We're also able to compare this research output to 223 others from the same source and published within six weeks on either side of this one. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.