Comparison between direct binding, competition and agglutination assays in the characterization of polyclonal anti-idiotypes against anti-HBs human monoclonal antibodies.

Polyclonal anti-idiotypic antibodies to human monoclonal anti-HBs antibodies (MoAb1) were raised in rabbits and designated Ab2-H1 and Ab2-H2. These Ab2 were characterized using three assays. A direct binding ELISA evaluated specificity towards a panel of human monoclonal antibodies and gamma globulins. Competition radioimmunoassay (CRIA) revealed Ab2 specificities towards Ab1 antigen binding sites by inhibition of HBsAg/Ab1 binding. Ab2-H1 and Ab2-H2 had comparable reactivities in ELISA and CRIA, whereas, using affinity purified Ab2, a fast (10 min) agglutination test (Spherotest) revealed different Ab1/Ab2 binding properties. Ab2-H1 reacted in this Spherotest with the Ab1 against which it was known to be specific (Ab1-H1), whereas in the same assay Ab2-H2 showed no activity towards the variable regions of the Ab1 used for its production (Ab1-H2). When injected into rabbits Ab2-H1 induced anti-HBs Ab3 antibodies but Ab2-H2 did not, thereby confirming the assay results.

AIDS: an immune response against the immune system. Role of a precise tridimensional molecular mimicry.

This study describes some of the expected autoimmune consequences of a recently described virus-host molecular mimicry in patients infected with human immunodeficiency virus (HIV). Some physical and structural analogies have been recently identified between some precise antigenic sites of the trimeric ectodomain of the transmembrane envelope protein of AIDS-associated lentiviruses (HIV, Simian immunodeficiency virus and feline immunodeficiency virus) and some precise and crucial interleukin 2 (IL-2) antigenic sites of the corresponding infected species (man, monkey, cat). As expected, HIV-positive sera recognize human IL-2, and a cross-reactivity was found between the structurally and physically analogous antigenic sites of GP41 (HIV1) and human IL-2. The possible impact on AIDS-associated disorders of this tridimensional GP41 (HIV1)/human IL-2 molecular mimicry is suggested.

Molecular mimicry between the trimeric ectodomain of the transmembrane protein of immunosuppressive lentiviruses (HIV-SIV-FIV) and interleukin 2.

This work shows the presence of structural and physical analogies between some precise sites of the trimeric ectodomain of the transmembrane envelope glycoproteins of the HIV, SIV and FIV viruses and some precise sites of the interleukin 2 of the corresponding infected species (man, monkey, cat, respectively). In all the cases examined, the ectodomains of GP41 (HIV-SIV) and GP36 (FIV), because of their trimeric structure, place in the same spatial configuration the same amino acids clusters as the IL-2 amino acids clusters interacting with two, or even three, of the alpha, beta and gamma subunits of the IL-2 receptor. The molecular mimicry identified between the viral transmembrane glycoprotein and IL-2 is probably most useful for the virus and seems to be specific of each species; it is presumably due to a strategy common to the retroviruses associated with AIDS (HIV, SIV, FIV).

A new device for specific extracorporeal immunoadsorption of anti-DNA antibodies. In vitro and in vivo results.

Selective removal of anti-DNA antibodies could be an alternative to therapeutic plasma exchange in patients with active systemic lupus erythematosus. The method is based on the immobilization by covalent binding of double-stranded, calibrated, 0.3-kb DNA fragments on a microporous, methylated, polyacrylonitrile membrane. This enables linkage of 60 micrograms of DNA per cm2 of apparent surface area. In vitro, perfusion of 100 ml of plasma maintained at 37 degrees C through 650 cm2 of dsDNA linked to the membrane, at a flow rate of 1.5 ml/min for 60 min, resulted in the removal of 49-89% of anti-DNA IgG without any changes in plasma protein or IgG levels. During a therapeutic plasma exchange, perfusion of the plasma through 1.5 m2 of membrane, at a flow rate of 25 ml/min, initially removed 92% of the anti-dsDNA antibodies entering the adsorbent and 25% at 120 min, indicating a progressive saturation of the binding capacity. Clinical immunoadsorption, at a plasma flow rate of 20-40 ml/min through 2 m2 of membrane, removed more than 50% of anti-dsDNA IgG within 60 min. Microporous membranes are able to irreversibly bind large amounts of antigenic ligands, and enable the selective removal of pathogenetic immunoglobulins or circulating factors.