The Journal of Experimental Medicine
Fluorescence In Vivo Endomicroscopy
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 2 February 2004. doi:10.1084/jem.20030132
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 3, 381-398
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 252K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Liang, Z.
Right arrow Articles by Mohan, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liang, Z.
Right arrow Articles by Mohan, C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Pathogenic Profiles and Molecular Signatures of Antinuclear Autoantibodies Rescued from NZM2410 Lupus Mice

Zhiyan Liang1, Chun Xie1, Cui Chen1, Desi Kreska1, Kelvin Hsu1, Liunan Li1, Xin J. Zhou3, and Chandra Mohan1,2

1 Simmons Arthritis Research Center, University of Texas Southwestern Medical School, Dallas, TX 75390
2 Center for Immunology, University of Texas Southwestern Medical School, Dallas, TX 75390
3 Department of Pathology, University of Texas Southwestern Medical School, Dallas, TX 75390

Address correspondence to Chandra Mohan, Simmons Arthritis Research Center, Internal Medicine/Rheumatology, University of Texas Southwestern Medical School, Mail Code 8884, Y8.204, 5323 Harry Hines Blvd., Dallas, TX 75390. Phone: (214) 648-9675; Fax: (214) 648-7995; email: Chandra.mohan{at}utsouthwestern.edu

Two outstanding questions concerning antinuclear antibodies (ANAs) in lupus involve their pathogenic potential and their molecular signatures. To address these questions, a panel of 56 antinuclear and 47 nonnuclear binding monoclonal antibodies was rescued from four seropositive NZM2410 lupus mice. The monoclonals varied in their reactivity to nucleosomes, ssDNA, dsDNA, and glomerular substrate. A large fraction of the antibodies demonstrated apparent polyreactivity (to DNA, histones, and glomerular antigens) due to bound, DNase-1 sensitive nuclear antigenic bridges. Although nephrophilic immunoglobulin (Ig) M and IgG antibodies were the most pathogenic, the dsDNA-binding antibodies were modestly so; in contrast, antinucleosome antibodies were clearly not pathogenic. Compared with the nonnuclear antigen-binding monoclonal antibodies rescued from the same mice, ANAs exhibited increased utilization of VH5/7183 genes and highly cationic heavy chain (HC) CDR3 regions. Most intriguingly, the CDR3 regions of the ANAs exhibited alternating arginine/lysine peaks at H96, H98, and H100, with neutral troughs at H95, H97, and H99. To summarize, glomerular-binding anti-dsDNA antibodies appear to be the most pathogenic variety of lupus autoantibodies. The presence of an alternating charge pattern in their HC CDR3 regions appears to be a prominent hallmark of ANAs.

Key Words: CDR3 • nucleosomes • anti-DNA • New Zealand mice • nephritis

Abbreviations used in this paper: ANA, antinuclear antibody; BUN, blood urea nitrogen; HC, heavy chain; LC, light chain; pI, isoelectric point; rt, room temperature; SLE, systemic lupus erythematosus.

The online version of this article includes supplemental material.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS