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CXCL13 antibody for the treatment of autoimmune disorders

Overview of attention for article published in BMC Immunology, January 2015
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Title
CXCL13 antibody for the treatment of autoimmune disorders
Published in
BMC Immunology, January 2015
DOI 10.1186/s12865-015-0068-1
Pubmed ID
Authors

Ekaterina Klimatcheva, Tracy Pandina, Christine Reilly, Sebold Torno, Holm Bussler, Maria Scrivens, Alan Jonason, Crystal Mallow, Michael Doherty, Mark Paris, Ernest S Smith, Maurice Zauderer

Abstract

Homeostatic B Cell-Attracting chemokine 1 (BCA-1) otherwise known as CXCL13 is constitutively expressed in secondary lymphoid organs by follicular dendritic cells (FDC) and macrophages. It is the only known ligand for the CXCR5 receptor, which is expressed on mature B cells, follicular helper T cells (Tfh), Th17 cells and regulatory T (Treg) cells. Aberrant expression of CXCL13 within ectopic germinal centers has been linked to the development of autoimmune disorders (e.g. Rheumatoid Arthritis, Multiple Sclerosis, Systemic Lupus Erythematosis). We, therefore, hypothesized that antibody-mediated disruption of the CXCL13 signaling pathway would interfere with the formation of ectopic lymphoid follicles in the target organs and inhibit autoimmune disease progression. This work describes pre-clinical development of human anti-CXCL13 antibody MAb 5261 and includes therapeutic efficacy data of its mouse counterpart in murine models of autoimmunity. We developed a human IgG1 monoclonal antibody, MAb 5261 that specifically binds to human, rodent and primate CXCL13 with an affinity of approximately 5 nM and is capable of neutralizing the activity of CXCL13 from these various species in in vitro functional assays. For in vivo studies we have engineered a chimeric antibody to contain the same human heavy and light chain variable genes along with mouse constant regions. Treatment with this antibody led to a reduction in the number of germinal centers in mice immunized with 4-Hydroxy-3-nitrophenylacetyl hapten conjugated to Keyhole Limpet Hemocyanin (NP-KLH) and, in adoptive transfer studies, interfered with the trafficking of B cells to the B cell areas of mouse spleen. Furthermore, this mouse anti-CXCL13 antibody demonstrated efficacy in a mouse model of Rheumatoid arthritis (Collagen-Induced Arthritis (CIA)) and Th17-mediated murine model of Multiple Sclerosis (passively-induced Experimental Autoimmune Encephalomyelitis (EAE)). We developed a novel therapeutic antibody targeting CXCL13-mediated signaling pathway for the treatment of autoimmune disorders.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 87 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 87 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 22 25%
Researcher 21 24%
Student > Master 13 15%
Student > Bachelor 7 8%
Student > Doctoral Student 4 5%
Other 13 15%
Unknown 7 8%
Readers by discipline Count As %
Medicine and Dentistry 23 26%
Agricultural and Biological Sciences 19 22%
Biochemistry, Genetics and Molecular Biology 14 16%
Immunology and Microbiology 12 14%
Neuroscience 3 3%
Other 10 11%
Unknown 6 7%

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 16 January 2016.
All research outputs
#9,590,549
of 15,075,497 outputs
Outputs from BMC Immunology
#266
of 480 outputs
Outputs of similar age
#128,169
of 234,955 outputs
Outputs of similar age from BMC Immunology
#1
of 1 outputs
Altmetric has tracked 15,075,497 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 480 research outputs from this source. They receive a mean Attention Score of 3.3. This one is in the 32nd percentile – i.e., 32% 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 234,955 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them