Anestesia en un caso de síndrome de bardet-biedl / Anesthesia in a case of Bardet-Biedl syndrome

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Histones interact with anionic phospholipids with high avidity; its relevance for the binding of histone-antihistone immune complexes.

Antibodies recognizing anionic phospholipids have been described in systemic lupus erythematosus (SLE) and other autoimmune diseases. Recent studies have shown that some of these antibodies may recognize a cardiolipin-binding protein (apolipoprotein H) rather than phospholipids. A similar possibility is conceivable for other cardiolipin-binding proteins that are targets of autoantibodies. In this study we have addressed whether this might be the case for histones, a set of highly cationic and widely distributed proteins that react in a well known autoantibody system. Our results indicate that: (i) histones bind to anionic phospholipids (cardiolipin and phosphatidylserine) with high avidity, but not to zwitterionic phospholipids (phosphatidylcholine); (ii) monoclonal and polyclonal antihistone antibodies recognize histones bound to cardiolipin; (iii) the addition of histones to serum samples containing antihistone antibodies often enhances their anticardiolipin reactivity. In addition, we have found that antihistone-producing hybridomas derived from MRL-lpr mice may show anticardiolipin activity due to the presence of histones in the cell culture supernatants with the resultant formation of immune complexes. Taken together, the results suggest a potential role for histones in the anti-cardiolipin activity detected in sera containing antihistone antibodies. These histone-phospholipid interactions should be taken into account when evaluating the pathogenic effects of antihistone antibodies or other autoantibodies reacting with nuclear components (e.g. nucleosomes) containing histones.

Inhibition of histone/anti-histone reactivity by histone-binding serum components; differential effect on anti-H1 versus anti-H2B antibodies.

IgG fractions were purified on a protein G-agarose column from sera of both systemic lupus erythematosus (SLE) patients and healthy donors. All IgG fractions, after elution with 0.5 M acetic acid, reacted with histones in an anti-histone ELISA assay, and IgG anti-histone activity was in all instances higher in the IgG fraction than in the corresponding whole serum. This was shown to be due to the presence in serum of histone-binding components that inhibited IgG binding to histones. Both normal human and SLE patients' sera had these histone-binding components, and disparity between serum-positive and -negative anti-histone antibody (AHA) tests was not dependent on differences in the blocking capacity but on IgG antibody levels and avidity. Interaction of normal serum IgG fraction with all five histones was of low avidity, whereas interaction of IgG from AHA-positive SLE sera with both H1 and H2B had high avidity. Low-affinity antibodies to every histone fraction, but also high-affinity anti-H1 antibodies, were preferentially inhibited. Our data indicate that several serum protein components are inhibiting histone/anti-histone interaction and may play a protective role against both high-affinity anti-H1 antibodies present in SLE patients, and natural, low-affinity, anti-histone antibodies. As some acute phase proteins, notably C-reactive protein, bind to histones, it is conceivable that they play such a role. High-affinity anti-H2B antibodies, present in some SLE patients, and not inhibited by these serum components, may, on the other hand, participate in the pathogenesis of the disease.

Evidence that a putative anti-idiotypic monoclonal antibody may actually be recognizing circulating immune complexes.

Murine monoclonal antibodies (mAb) reacting with affinity-purified antihistone antibodies (AHA) from serum of a patient with systemic lupus erythematosus (SLE) were obtained. One of them, 8B3, was initially considered to recognize idiotypic (Id) determinants in AHA since (a) it reacted with AHA but not with control IgG; (b) this reactivity could be inhibited using affinity-purified AHA, but not with control IgG or whole serum; (c) affinity-isolated 8B3+ antibodies showed antihistone activity and not other activities tested so far; (d) antihistone activity due to 8B3+, but not that of 8B3- from the same serum, could be fully inhibited by the presence of 8B3 mAb in the antihistone assay and (e) serum levels of 8B3 reactivity were higher than normal in SLE patients with AHA (56%), in contrast with SLE patients without AHA (6%). From these results it was deduced that 8B3 defined a cross-reactive Id shared by a subset of AHA in SLE patients. However, the present results suggest that (a) 8B3 mAb did not recognize AHA or Ig, but did recognize a 55 kDa histone-binding protein; (b) this 55 kDa protein was present free at low concentration in all human sera, but also associated with IgG in 8B3+ SLE sera and (c) these complexes are responsible for the false positive results in the antihistone assay as shown for DNA/anti-DNA complexes. Thus, mAbs recognizing the non-Ig moiety of circulating immune complexes may resemble anti-Id antibodies with features of the so-called epibodies. These immune complexes may be responsible for false positive results and caution should be exercised in the interpretation of results.