Repertoire cloning of lupus anti-DNA autoantibodies

Paul Roben, Shana M. Barbas, Laura Sandoval, Jean Michel Lecerf, B. David Stollar, Alan Solomon, Gregg J. Silverman

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

To investigate the autoantibody repertoire associated with SLE, we have created phage display IgG Fab libraries from two clinically active SLE patients and from the healthy identical twin of one of these patients. The libraries from the lupus discordant twins were found to both include unusually large representations of the V(H)5 gene family. By panning with DNA, the SLE libraries each yielded IgG anti-doublestranded (ds) DNA autoantibodies, which are characteristic of lupus disease. These included a V(H)5 autoantibody from the affected twin, that has a targeted cluster of mutations that potentially improves binding affinity. The recovered IgG anti- dsDNA autoantibodies expressed the same idiotypes associated with the in vivo IgG anti-dsDNA response of the respective SLE donor. Heavy-light chain shuffling experiments demonstrated a case in which the in vitro creation of anti-dsDNA binding activity required restrictive pairing of a heavy chain with Vλ light chains similar to those in circulating anti-dsDNA autoantibodies. By contrast, IgG anti-ds autoantibodies could not be recovered from the library from the healthy twin, or from shuffled libraries with heavy chains from the healthy twin. These repertoire analyses illustrate how inheritance and somatic processes interplay to produce lupus-associated IgG autoantibodies.

Original languageEnglish (US)
Pages (from-to)2827-2837
Number of pages11
JournalJournal of Clinical Investigation
Volume98
Issue number12
DOIs
StatePublished - Dec 15 1996

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Autoantibodies
Organism Cloning
DNA
Libraries
Immunoglobulin G
Monozygotic Twins
Gene Library
Bacteriophages
Tissue Donors
Light
Mutation
anti-IgG
Genes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Roben, P., Barbas, S. M., Sandoval, L., Lecerf, J. M., Stollar, B. D., Solomon, A., & Silverman, G. J. (1996). Repertoire cloning of lupus anti-DNA autoantibodies. Journal of Clinical Investigation, 98(12), 2827-2837. https://doi.org/10.1172/JCI119111

Repertoire cloning of lupus anti-DNA autoantibodies. / Roben, Paul; Barbas, Shana M.; Sandoval, Laura; Lecerf, Jean Michel; Stollar, B. David; Solomon, Alan; Silverman, Gregg J.

In: Journal of Clinical Investigation, Vol. 98, No. 12, 15.12.1996, p. 2827-2837.

Research output: Contribution to journalArticle

Roben, P, Barbas, SM, Sandoval, L, Lecerf, JM, Stollar, BD, Solomon, A & Silverman, GJ 1996, 'Repertoire cloning of lupus anti-DNA autoantibodies', Journal of Clinical Investigation, vol. 98, no. 12, pp. 2827-2837. https://doi.org/10.1172/JCI119111
Roben P, Barbas SM, Sandoval L, Lecerf JM, Stollar BD, Solomon A et al. Repertoire cloning of lupus anti-DNA autoantibodies. Journal of Clinical Investigation. 1996 Dec 15;98(12):2827-2837. https://doi.org/10.1172/JCI119111
Roben, Paul ; Barbas, Shana M. ; Sandoval, Laura ; Lecerf, Jean Michel ; Stollar, B. David ; Solomon, Alan ; Silverman, Gregg J. / Repertoire cloning of lupus anti-DNA autoantibodies. In: Journal of Clinical Investigation. 1996 ; Vol. 98, No. 12. pp. 2827-2837.
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