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Positional cloning of the Igl genes controlling rheumatoid factor production and allergic bronchitis in rats

Rintisch, Carola; Ameri, Jacqueline LU ; Olofsson, Peter; Luthman, Holger LU and Holmdahl, Rikard (2008) In Proceedings of the National Academy of Sciences 105(37). p.14005-14010
Abstract
Rheumatoid factors (RF), autoantibodies that bind the Fc region of IgG, are one of the major diagnostic marker in rheumatoid arthritis (RA) but occur with lower frequency also in other infectious and inflammatory conditions. Through positional cloning of the previously described quantitative trait locus (QTL) Rf1 in congenic and advanced intercrossed rats, we identified the Ig lambda light chain locus as a locus that regulates the production of RF in rats. The congenic rats produce RF-Ig lambda and have significant higher levels of RF-IgG and RF-IgM in serum, while the DA rat has an impaired RF production and does not produces RF-Ig lambda. Thus, we could investigate the role of RF in pristane-induced arthritis (PIA) as well as... (More)
Rheumatoid factors (RF), autoantibodies that bind the Fc region of IgG, are one of the major diagnostic marker in rheumatoid arthritis (RA) but occur with lower frequency also in other infectious and inflammatory conditions. Through positional cloning of the previously described quantitative trait locus (QTL) Rf1 in congenic and advanced intercrossed rats, we identified the Ig lambda light chain locus as a locus that regulates the production of RF in rats. The congenic rats produce RF-Ig lambda and have significant higher levels of RF-IgG and RF-IgM in serum, while the DA rat has an impaired RF production and does not produces RF-Ig lambda. Thus, we could investigate the role of RF in pristane-induced arthritis (PIA) as well as ovalbumin-induced airway inflammation. We show that there was no difference in the development and severity of PIA between congenic and parental DA rats, suggesting that RIP using lambda light chains have no impact on PIA. However, the RF producing congenic rats developed a more severe airway inflammation as indicated in the significantly increased number of eosinophils in bronchoalveolar lavage fluid as well as total IgE in serum. In addition, RF congenic rats had a significantly enhanced immune response toward OVA due to increased OVA-Igk but not OVA-IgI antibodies, suggesting a possible involvement of RF in the regulation of the humoral immune response. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
rheumatoid, OVA-induced airway inflammation, quantitative trait locus, arthritis, congenic animals
in
Proceedings of the National Academy of Sciences
volume
105
issue
37
pages
14005 - 14010
publisher
National Acad Sciences
external identifiers
  • wos:000259438500059
  • scopus:52949090405
ISSN
1091-6490
DOI
10.1073/pnas.0803956105
language
English
LU publication?
yes
id
e7a3ed0a-4eba-4a11-b9b3-1361f9c4f495 (old id 1286971)
date added to LUP
2009-01-28 11:03:34
date last changed
2017-04-16 03:24:45
@article{e7a3ed0a-4eba-4a11-b9b3-1361f9c4f495,
  abstract     = {Rheumatoid factors (RF), autoantibodies that bind the Fc region of IgG, are one of the major diagnostic marker in rheumatoid arthritis (RA) but occur with lower frequency also in other infectious and inflammatory conditions. Through positional cloning of the previously described quantitative trait locus (QTL) Rf1 in congenic and advanced intercrossed rats, we identified the Ig lambda light chain locus as a locus that regulates the production of RF in rats. The congenic rats produce RF-Ig lambda and have significant higher levels of RF-IgG and RF-IgM in serum, while the DA rat has an impaired RF production and does not produces RF-Ig lambda. Thus, we could investigate the role of RF in pristane-induced arthritis (PIA) as well as ovalbumin-induced airway inflammation. We show that there was no difference in the development and severity of PIA between congenic and parental DA rats, suggesting that RIP using lambda light chains have no impact on PIA. However, the RF producing congenic rats developed a more severe airway inflammation as indicated in the significantly increased number of eosinophils in bronchoalveolar lavage fluid as well as total IgE in serum. In addition, RF congenic rats had a significantly enhanced immune response toward OVA due to increased OVA-Igk but not OVA-IgI antibodies, suggesting a possible involvement of RF in the regulation of the humoral immune response.},
  author       = {Rintisch, Carola and Ameri, Jacqueline and Olofsson, Peter and Luthman, Holger and Holmdahl, Rikard},
  issn         = {1091-6490},
  keyword      = {rheumatoid,OVA-induced airway inflammation,quantitative trait locus,arthritis,congenic animals},
  language     = {eng},
  number       = {37},
  pages        = {14005--14010},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Positional cloning of the Igl genes controlling rheumatoid factor production and allergic bronchitis in rats},
  url          = {http://dx.doi.org/10.1073/pnas.0803956105},
  volume       = {105},
  year         = {2008},
}