A human systemic lupus erythematosus-related anti-cardiolipin/single-stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51P1 VH gene.
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| Abstract |
We report the Ig H and L chain V region sequences from the cDNAs encoding a monoclonal human IgG anti-cardiolipin/ssDNA autoantibody (R149) derived from a patient with active SLE. Comparison with the germ-line V-gene repertoire of this patient revealed that R149 likely arose as a consequence of an Ag-driven selection process. The Ag-binding portions of the V regions were characterized by a high number of arginine residues, a property that has been associated with anti-dsDNA autoantibodies from lupus-prone mice and patients with SLE. The VH gene encoding autoantibody R149 was a somatically mutated variant of the 51P1 gene segment, which is frequently associated with the restricted fetal B cell repertoire, malignant CD5 B cells, and natural autoantibodies. These data suggest that in SLE patients a common antigenic stimulus may evoke anti-DNA and anti-cardiolipin autoantibodies and provide further evidence that a small set of developmentally restricted VH genes can give rise to disease-associated autoantibodies through Ag-selected somatic mutations.
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| Authors | J H Van Es, H Aanstoot, F H Gmelig-Meyling, R H Derksen, T Logtenberg |
| Journal | Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 149 Issue 6 Pg. 2234-40 (Sep 15 1992) ISSN: 0022-1767 [Print] United States |
| PMID | 1517580 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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