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Articular, monoclonal gamma3 heavy-chain deposition disease: characterization of a partially deleted heavy-chain gene and its protein product synthesized in vivo and in vitro.

Thompson, Keith M; Sletten, Knut; Brandtzaeg, Per; Källberg, Eva LU ; Wien, Tale Norbye and Husby, Gunnar (2003) In Arthritis and Rheumatism 48(11). p.3266-3271
Abstract
Objective

A patient presented with heavy-chain deposition disease (HCDD), exhibiting severe erosive polyarthropathy caused by synovial deposits of abnormal monoclonal, heavily deleted free 3 heavy chains lacking the VH and CH1 domains. The absence of VH was surprising, since it is considered important for pathogenic tissue deposition. This study was undertaken to analyze the genetic structure of the heavy chain, the protein product synthesized in vitro, and that deposited in the synovium in comparison with the serum and urinary proteins.



Methods

Hybridomas were made by fusion of blood and bone marrow mononuclear cells with mouse myeloma cells. Cloned B cell hybridomas secreting 3 were selected and... (More)
Objective

A patient presented with heavy-chain deposition disease (HCDD), exhibiting severe erosive polyarthropathy caused by synovial deposits of abnormal monoclonal, heavily deleted free 3 heavy chains lacking the VH and CH1 domains. The absence of VH was surprising, since it is considered important for pathogenic tissue deposition. This study was undertaken to analyze the genetic structure of the heavy chain, the protein product synthesized in vitro, and that deposited in the synovium in comparison with the serum and urinary proteins.



Methods

Hybridomas were made by fusion of blood and bone marrow mononuclear cells with mouse myeloma cells. Cloned B cell hybridomas secreting 3 were selected and analyzed by polymerase chain reaction. Purified hybridoma Ig was sequenced by Edman degradation. Antiserum raised to a peptide corresponding to residues 2-15 of the truncated VH was used in Western blots of synovial tissue.



Results

The hybridomas secreted free 3 chains consisting of a VH4 gene truncated 21 nucleotides into the first complementarity-determining region and then reading straight into the hinge region. The amino acid sequence confirmed the presence of residues 1-32 of the VH4 gene. Immunoblotting of synovial tissue showed the presence of Ig with truncated VH.



Conclusion

The 3 heavy chain had a deletion of VH from codon 33 and of the entire CH1. In vivo, the 32 VH amino acids were proteolytically degraded. In the joint, however, the 32 residues of VH remained intact, consistent with a pathogenic role of VH for tissue deposition. To our knowledge, this is the first reported case of HCDD causing an erosive, polyarticular arthropathy as the dominating clinical feature. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arthritis and Rheumatism
volume
48
issue
11
pages
3266 - 3271
publisher
John Wiley & Sons
external identifiers
  • scopus:0242411774
ISSN
1529-0131
DOI
10.1002/art.11298
language
English
LU publication?
yes
id
943efe00-6388-4b6a-95f7-c342831e561b (old id 1128214)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/14613292?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
date added to LUP
2008-06-02 16:03:16
date last changed
2018-01-07 06:02:36
@article{943efe00-6388-4b6a-95f7-c342831e561b,
  abstract     = {Objective <br/><br>
A patient presented with heavy-chain deposition disease (HCDD), exhibiting severe erosive polyarthropathy caused by synovial deposits of abnormal monoclonal, heavily deleted free 3 heavy chains lacking the VH and CH1 domains. The absence of VH was surprising, since it is considered important for pathogenic tissue deposition. This study was undertaken to analyze the genetic structure of the heavy chain, the protein product synthesized in vitro, and that deposited in the synovium in comparison with the serum and urinary proteins. <br/><br>
<br/><br>
Methods <br/><br>
Hybridomas were made by fusion of blood and bone marrow mononuclear cells with mouse myeloma cells. Cloned B cell hybridomas secreting 3 were selected and analyzed by polymerase chain reaction. Purified hybridoma Ig was sequenced by Edman degradation. Antiserum raised to a peptide corresponding to residues 2-15 of the truncated VH was used in Western blots of synovial tissue. <br/><br>
<br/><br>
Results <br/><br>
The hybridomas secreted free 3 chains consisting of a VH4 gene truncated 21 nucleotides into the first complementarity-determining region and then reading straight into the hinge region. The amino acid sequence confirmed the presence of residues 1-32 of the VH4 gene. Immunoblotting of synovial tissue showed the presence of Ig with truncated VH. <br/><br>
<br/><br>
Conclusion <br/><br>
The 3 heavy chain had a deletion of VH from codon 33 and of the entire CH1. In vivo, the 32 VH amino acids were proteolytically degraded. In the joint, however, the 32 residues of VH remained intact, consistent with a pathogenic role of VH for tissue deposition. To our knowledge, this is the first reported case of HCDD causing an erosive, polyarticular arthropathy as the dominating clinical feature.},
  author       = {Thompson, Keith M and Sletten, Knut and Brandtzaeg, Per and Källberg, Eva and Wien, Tale Norbye and Husby, Gunnar},
  issn         = {1529-0131},
  language     = {eng},
  number       = {11},
  pages        = {3266--3271},
  publisher    = {John Wiley & Sons},
  series       = {Arthritis and Rheumatism},
  title        = {Articular, monoclonal gamma3 heavy-chain deposition disease: characterization of a partially deleted heavy-chain gene and its protein product synthesized in vivo and in vitro.},
  url          = {http://dx.doi.org/10.1002/art.11298},
  volume       = {48},
  year         = {2003},
}