Evidence map›Paper›PMID 25101087›Full record

ArticleFrontiers in immunology2014

Accumulation of VH Replacement Products in IgH Genes Derived from Autoimmune Diseases and Anti-Viral Responses in Human.

Miles D Lange, Lin Huang, Yangsheng Yu, Song Li, Hongyan Liao, Michael Zemlin, Kaihong Su, Zhixin Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Heavy-chain receptor editing unbound.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  7. VH replacement in primary immunoglobulin repertoire diversification.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Miles D LangeDepartment of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE , USA.
Lin HuangDepartment of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE , USA.
Yangsheng YuDepartment of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE , USA.
Song LiDepartment of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE , USA.
Hongyan LiaoDepartment of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE , USA.
Michael ZemlinDepartment of Pediatrics, Philipps-University Marburg , Marburg , Germany.
Kaihong SuDepartment of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE , USA ; The Eppley Cancer Institute, University of Nebraska Medical Center , Omaha, NE , USA ; Department of Internal Medicine, University of Nebraska Medical Center , Omaha, NE , USA.
Zhixin ZhangDepartment of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE , USA ; The Eppley Cancer Institute, University of Nebraska Medical Center , Omaha, NE , USA.

Funding

Excessive Receptor Editing and Generation of Autoreactive Antibodies in SLER01AI076475 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI ZHANG, ZHIXIN · 2008 to 2012
$1.6M
Novel Neutrophil Autoantigens in Systemic Lupus ErythematosusR01AR059351 · NIAMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI SU, KAIHONG · 2011 to 2015
$1.5M
Molecular Regulation of VH Gene Replacement in Human Immature B CellsR01AI074948 · NIAID · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI ZHANG, ZHIXIN · 2008 to 2012
$1.5M
NIAID NIH HHS R01 AI074948NIAID NIH HHS R01 AI076475NIAMS NIH HHS R01 AR059351
6 · The paper itself

Abstract

VH replacement refers to RAG-mediated secondary recombination of the IgH genes, which renews almost the entire VH gene coding region but retains a short stretch of nucleotides as a VH replacement footprint at the newly generated VH-DH junction. To explore the biological significance of VH replacement to the antibody repertoire, we developed a Java-based VH replacement footprint analyzer program and analyzed the distribution of VH replacement products in 61,851 human IgH gene sequences downloaded from the NCBI database. The initial assignment of the VH, DH, and JH gene segments provided a comprehensive view of the human IgH repertoire. To our interest, the overall frequency of VH replacement products is 12.1%; the frequencies of VH replacement products in IgH genes using different VH germline genes vary significantly. Importantly, the frequencies of VH replacement products are significantly elevated in IgH genes derived from different autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and allergic rhinitis, and in IgH genes encoding various autoantibodies or anti-viral antibodies. The identified VH replacement footprints preferentially encoded charged amino acids to elongate IgH CDR3 regions, which may contribute to their autoreactivities or anti-viral functions. Analyses of the mutation status of the identified VH replacement products suggested that they had been actively involved in immune responses. These results provide a global view of the distribution of VH replacement products in human IgH genes, especially in IgH genes derived from autoimmune diseases and anti-viral immune responses.

Indexed as

antibodyanti-viral responseautoimmune diseaseB-cellcryptic RSSIgH genesVH replacementVH replacement footprint

Identifiers

PMID25101087
PMCPMC4105631

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.