Analysis of human antitopoisomerase-I idiotypes
DNA Topoisomerases, Type I
Antibodies to topoisomerase-I are present in approximately 26% of patients with scleroderma and are rarely found in patients with other diseases. In the current study, the expression of the antitopoisomerase-I (antitopo-I) idiotype from two scleroderma patients (E.M. and S.G.) and from a healthy individual (N.M.) were studied. Idiotype EM-SCL was restricted to the three classes of antitopo-I, whereas idiotypes SG-SCL and NM were found in all classes of antitopo-I as well as in their non-antitopo-I Igs. Sera from 9 of 10 antitopo-I-positive unrelated scleroderma patients expressed idiotype SG-SCL and some also expressed idiotype NM. Sera from N.M.'s 3 daughters and from 7 of 18 nonrelated normals expressed idiotype NM in the three immunoglobulin classes of non-antitopo-I. Two of the antitopo-I antibodies expressed a cross-reacting idiotype (CRI) that is present in non-antitopo-I antibodies from the same donor. Contrary to the natural CRI, SG-SCL's CRI is closely associated with the antigen binding site. Antitopo-I idiotypes are on the heavy chains. Like many other autoantibodies, Id-SG-SCL use VH4.2-1, DXP1, and JH4 in germline configuration.