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Identification of novel biomarker as citrullinated inter-alpha-trypsin inhibitor heavy chain 4, specifically increased in sera with experimental and rheumatoid arthritis

Overview of attention for article published in Arthritis Research & Therapy, April 2018
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (89th percentile)
  • High Attention Score compared to outputs of the same age and source (91st percentile)

Mentioned by

news
3 news outlets
blogs
1 blog

Citations

dimensions_citation
16 Dimensions

Readers on

mendeley
40 Mendeley
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Title
Identification of novel biomarker as citrullinated inter-alpha-trypsin inhibitor heavy chain 4, specifically increased in sera with experimental and rheumatoid arthritis
Published in
Arthritis Research & Therapy, April 2018
DOI 10.1186/s13075-018-1562-7
Pubmed ID
Authors

Hoshimi Kawaguchi, Isao Matsumoto, Atsumu Osada, Izumi Kurata, Hiroshi Ebe, Yuki Tanaka, Asuka Inoue, Naoto Umeda, Yuya Kondo, Hiroto Tsuboi, Yasuhiro Shinkai, Yoshito Kumagai, Akihito Ishigami, Takayuki Sumida

Abstract

Anticitrullinated protein antibodies (ACPA) and citrullinated proteins play key roles in the pathogenesis of rheumatoid arthritis (RA). Many candidate citrullinated antigens have been identified in joints, but citrullinated proteins in sera are mostly uncertain in patients with RA. We explored the expression of citrullinated proteins in joints and sera of experimental arthritis, and we further investigated their specific expression correlated with the disease activity in patients with RA. Citrullinated protein expression in tissues was examined by IHC in peptide glucose-6-phosphate isomerase-induced arthritis (pGIA). Serum citrullinated proteins from pGIA were examined by Western blotting, and the sequence was identified by MS. With the same methods, serum citrullinated proteins were analyzed in patients with RA, primary Sjögren's syndrome, systemic lupus erythematosus, and osteoarthritis as well as in healthy subjects, by Western blotting and MS. In patients with RA, the relationship between the expression of the identified protein (inter-alpha-trypsin inhibitor heavy chain 4 [ITIH4]) and clinical features was evaluated, and the levels of citrullinated ITIH4 were compared before and after biological treatment. The antibody response against citrullinated ITIH4 peptide was measured by enzyme-linked immunosorbent assay. Citrullinated proteins were detected specifically in arthritic joints and sera from pGIA relative to controls. In sera, a common band of citrullinated protein at 120 kDa was revealed, and it fluctuated in parallel with arthritis score of pGIA by Western blotting. Interestingly, in 82% of RA patient sera, similar bands of citrullinated protein were specifically detected. These proteins were identified as citrullinated ITIH4, and especially the R438 site was commonly citrullinated between mice and humans. Citrullinated ITIH4 levels were associated with clinical parameters such as C-reactive protein (CRP), rheumatoid factor, and Disease Activity Score in 28 joints as measured by CRP in patients with RA. Its levels were decreased in correlation with the reduction of disease activity score after effective treatment in patients with RA. Moreover, antibody response to citrullinated epitope in ITIH4 was specifically observed in patients with RA. Our results suggest that serum citrullinated ITIH4 was specifically increased in patients with RA and could be a novel biomarker for assessing disease activity in patients with RA.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 40 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 25%
Researcher 7 18%
Student > Master 6 15%
Student > Doctoral Student 2 5%
Other 2 5%
Other 5 13%
Unknown 8 20%
Readers by discipline Count As %
Medicine and Dentistry 11 28%
Biochemistry, Genetics and Molecular Biology 5 13%
Immunology and Microbiology 4 10%
Agricultural and Biological Sciences 3 8%
Pharmacology, Toxicology and Pharmaceutical Science 2 5%
Other 4 10%
Unknown 11 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 24. 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 13 May 2018.
All research outputs
#1,604,526
of 25,382,440 outputs
Outputs from Arthritis Research & Therapy
#219
of 3,381 outputs
Outputs of similar age
#34,526
of 343,274 outputs
Outputs of similar age from Arthritis Research & Therapy
#4
of 49 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 93rd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,381 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one has done particularly well, scoring higher than 93% of its peers.
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 343,274 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 49 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 91% of its contemporaries.