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Lupus autoantibodies to native DNA preferentially bind DNA presented on PolIV
Author(s) -
Kumar Sanjeev,
Bunting Karen A.,
Kalsi Jatinderpal,
Hinks John A.,
Latchman David S.,
Pearl Laurence H.,
Isenberg David A.
Publication year - 2005
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2005.02090.x
Subject(s) - lupus nephritis , autoantibody , antibody , systemic lupus erythematosus , anti dsdna antibodies , dna , lupus erythematosus , naked dna , immunology , monoclonal , context (archaeology) , biology , microbiology and biotechnology , serology , monoclonal antibody , medicine , pathology , genetics , disease , paleontology , plasmid
Summary While immunoglobulin G (IgG) antibodies to double‐stranded (ds)DNA are serological markers of systemic lupus erythematosus (SLE), not all antibodies to DNA (anti‐DNA) are able to cause tissue damage to a similar extent. It has been proposed that anti‐DNA‐induced renal damage could be linked to differences in the fine specificity of the antibodies. In an attempt to gain insight into their fine binding properties, we investigated the cross‐reactivity of two human lupus monoclonal IgG anti‐dsDNA (B3 and RH14) to a recently described Escherichia coli PolIV (a DNA polymerase). These autoantibodies possess distinct pathogenic properties in severe combined immunodeficient (SCID) mice. Although both antibodies cause proteinuria, only RH14 induces early histological features of lupus nephritis. Both RH14 and B3 bound PolIV; however, they exhibited a marked difference in their reactivity to the PolIV–dsDNA complex. Alhough RH14 exhibited significant activity to the complex, the binding of B3 to PolIV complexed with dsDNA was almost abolished. Furthermore, there was a significant difference in the way the lupus sera recognized naked dsDNA and that presented on PolIV. Although 67% of lupus sera bound naked dsDNA, ≈ 90% of these sera (93% calf thymus DNA; 90% synthetic oligonucleotide) reacted to the complex when dsDNA was presented on PolIV. Thus, the IgG anti‐dsDNA likely to exist in lupus patients may be distinguished into those that recognize dsDNA in the context of PolIV and those which do not. This difference in binding ability may help to distinguish those dsDNA antibodies that are more pathogenic.