Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phospholipids.

Abstract

The diversity of autoantibodies produced in systemic lupus erythematosus (SLE) 1 (1) differentiates this disease from other autoimmune disorders in which the autoantibodies react with a narrow range of antigenic determinants. In autoimmune thyrotoxicosis (2), myasthenia gravis (3), and autoimmune hemolytic anemia (4), as examples, the diversity of autoantibody reactions is limited by comparison with the serological findings in SLE. A typical lupus serum can react with nucleic acids (native or denatured DNA; RNA) and nucleoproteins (Sm and RNP antigens; ribosomes; nucleohistones), cell surface antigens, cardiolipin, and certain coagulant activities of the blood, but usually not with any organ-or receptor-specific autoantigens (reviewed in [1]). Therefore, there is restricted heterogeneity within the serological polymorphism of SLE. The extent of autoantibody diversity in SLE is of fundamental importance because it pertains to the widely held view that this disease is a result of a generalized disturbance of the immune system (5, 6).We have undertaken an analysis of the diversity of lupus autoantibodies by means of hybridoma technology (7,8). The advantage of this method over analysis of serum antibodies is that individual molecular species of autoantibody can be examined so that true diversity can be distinguished from cross-reactivity. The hybridomas under study were prepared by fusion of spleen cells from unimmunized MRL/1 mice with mouse myeloma cells. MRL/1 mice were chosen because they spontaneously develop a severe form of SLE and because they produce high levels of anti-DNA antibodies (9). Some of the hybridoma anti-DNA autoantibodies we prepared have an immunochemical preference for particular purine bases, whereas others react with a wide range of polynucleotides (8). The latter kind of autoantibody might be reactive with the sugar-phosphate backbone of nucleic acids, a structural feature of all polynucleotides (8). The sugar-phosphate backbone of nucleic acids consists of phosphate groups, in phosphodiester linkage, separated by three carbon atoms of adjacent sugar molecules. The phospholipid cardiolipin also contains phosphodiester-linked phos-

Mining the antibodyome for HIV-1–neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains

“…S4). Assessment of reactivity with other self antigens, including cardiolipin and a panel of anti-nuclear antigens (23)(24)(25), revealed that matched antibodies trended to lower mean reactivity (in 6/6 antibody doses for cardiolipin and 35/36 antibody doses for anti-nuclear antigens) but did not reach statistical significance, likely because mismatched antibodies exhibited a broad range of reactivities ( Fig. S5 and Tables S4 and S5).…”

β2‐Glycoprotein i reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome

“…Lafer et a1 (27) showed that monoclonal ssDNA antibodies from MRL-lpr mice cross-reacted with CL, PS, and PG. Koike et a1 (28) reported that anti-dsDNA activity in sera from patients with SLE was inhibited by CL.…”

“…Cross-reactivity of anti-DNA antibodies with CL has been demonstrated using sera and monoclonal anti-DNA antibodies from SLE-prone mice, from normal individuals, and from SLE patients (2,(25)(26)(27)(28)(29). However, the P,-GPI dependence of these antibodies has not been examined.…”

Anticardiolipin antibodies in patients with systemic lupus erythematosus

“…The prevalence and the clinical importance of these antibodies have also been discussed in relation to the occurrence of human and mouse monoclonal antibodies against denatured DNA, and their cross-reactivity with cardiolipin and other phospholipids (4)(5)(6).…”