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Relapsing polychondritis, induced in mice with matrilin 1, is an antibody- and complement-dependent disease

Hansson, AS; Johannesson, Martina LU ; Svensson, Lars LU ; Nandakumar, KS; Heinegård, Dick LU and Holmdahl, Rikard LU (2004) In American Journal of Pathology 164(3). p.959-966
Abstract
Relapsing polychondritis is an autoinumme disease that affects cartilage in the ear, nose, and respiratory tract. A pathogenic immune response has been proposed and antibodies to several cartilage proteins are detected in sera from these patients. To investigate the role of the humoral immune response in relapsing polychondritis, we used the matrilin-1-induced relapsing polychondritis model. Mice deficient of B cells (muMT) and mice congenic at the complement factor 5, were immunized with matrilin-1, a cartilage-specific protein mainly detected in the tracheal cartilage. To investigate the binding properties and tissue selection of matrilin-1-specific antibodies we produced matrilin-1-specific B-cell hybridomas. Although 83% of the muMT... (More)
Relapsing polychondritis is an autoinumme disease that affects cartilage in the ear, nose, and respiratory tract. A pathogenic immune response has been proposed and antibodies to several cartilage proteins are detected in sera from these patients. To investigate the role of the humoral immune response in relapsing polychondritis, we used the matrilin-1-induced relapsing polychondritis model. Mice deficient of B cells (muMT) and mice congenic at the complement factor 5, were immunized with matrilin-1, a cartilage-specific protein mainly detected in the tracheal cartilage. To investigate the binding properties and tissue selection of matrilin-1-specific antibodies we produced matrilin-1-specific B-cell hybridomas. Although 83% of the muMT heterozygous mice developed respiratory distress and erosive chondritis in the respiratory tract, none of the B-cell-deficient mice were susceptible to disease. In addition, we show that complement factor 5 is important for the induction of matrilin-1-induced relapsing polychondritis. Monoclonal matrilin-1-specific antibodies injected into neonatal mice bound specifically to cartilage of the respiratory tract and adult B-cell-deficient mice injected with the same antibodies developed erosive chondritis in the respiratory tract. We conclude that relapsing polychondritis can be mediated by a pathway involving tissue-specific antibodies and complement activation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Pathology
volume
164
issue
3
pages
959 - 966
publisher
American Society for Investigative Pathology
external identifiers
  • wos:000189164300021
  • pmid:14982849
  • scopus:1242271332
ISSN
1525-2191
language
English
LU publication?
yes
id
47d91355-a23b-4342-8e93-4d5260baec9a (old id 286833)
alternative location
http://ajp.amjpathol.org/cgi/content/abstract/164/3/959
date added to LUP
2007-10-29 13:34:41
date last changed
2017-11-19 03:24:59
@article{47d91355-a23b-4342-8e93-4d5260baec9a,
  abstract     = {Relapsing polychondritis is an autoinumme disease that affects cartilage in the ear, nose, and respiratory tract. A pathogenic immune response has been proposed and antibodies to several cartilage proteins are detected in sera from these patients. To investigate the role of the humoral immune response in relapsing polychondritis, we used the matrilin-1-induced relapsing polychondritis model. Mice deficient of B cells (muMT) and mice congenic at the complement factor 5, were immunized with matrilin-1, a cartilage-specific protein mainly detected in the tracheal cartilage. To investigate the binding properties and tissue selection of matrilin-1-specific antibodies we produced matrilin-1-specific B-cell hybridomas. Although 83% of the muMT heterozygous mice developed respiratory distress and erosive chondritis in the respiratory tract, none of the B-cell-deficient mice were susceptible to disease. In addition, we show that complement factor 5 is important for the induction of matrilin-1-induced relapsing polychondritis. Monoclonal matrilin-1-specific antibodies injected into neonatal mice bound specifically to cartilage of the respiratory tract and adult B-cell-deficient mice injected with the same antibodies developed erosive chondritis in the respiratory tract. We conclude that relapsing polychondritis can be mediated by a pathway involving tissue-specific antibodies and complement activation.},
  author       = {Hansson, AS and Johannesson, Martina and Svensson, Lars and Nandakumar, KS and Heinegård, Dick and Holmdahl, Rikard},
  issn         = {1525-2191},
  language     = {eng},
  number       = {3},
  pages        = {959--966},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {Relapsing polychondritis, induced in mice with matrilin 1, is an antibody- and complement-dependent disease},
  volume       = {164},
  year         = {2004},
}