PubMed · 2462848
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A J Steck, E Nardelli. 1988. Paraneoplastic autoimmunity.. https://doi.org/10.1111/j.1749-6632.1988.tb27054.x
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Is the structural repertoire of immunoglobulins free to adopt an almost infinite number of conformations to build the diversity of the immune response or does it take advantage of only a few conformations? In this paper we study this question by applying the canonical structure model to characterize the structural repertoire of immunoglobulins. The results found, indicate that only ten combinations out of the 300 possible different canonical structure classes (combinations of canonical structures), make up 87% of 381 sequences analyzed. This suggests that the structural repertoire of immunoglobulins is restricted to the preferential use of a small number of canonical structure classes. The possible functional significance of these results was studied by analyzing the correspondence between the observed canonical structural repertoire implicit in Ig sequences and the types of antigens recognized. Two different sets of canonical structure classes were distinguished: one with preference for some specific types of antigens like proteins, polysaccharides or haptens, and the other with multi-specific binding capabilities. Analysis of antibodies of known three-dimensional structure shows that for two specific classes, the canonical conformations of H2 and L1 determine the geometrical characteristics of the antigen-binding site, while at least in one multi-specific class, the changes in the general geometry of the antigen-binding site are produced by different conformations of H3. Implications of these results for the molecular recognition process mediated by immunoglobulins are discussed.
In a serological laboratory with a routine service for determining autoantibodies to human neutrophils, antibodies giving a selective or preferential reaction with the nucleus or perinuclear area of neutrophils are not uncommon. The aim of this study was to look for clinical correlates with the presence of such neutrophil-reactive autoantibodies. The specificity of such antibodies for nuclear or cytoplasmic antigens was studied in 65 consecutive sera displaying nuclear/perinuclear reactivity at a titre of at least 80 using the indirect immunofluorescence technique (IIF) on ethanol-fixed leucocytes. The sera were also investigated by IIF on formalin-acetone fixed leucocytes and on HEp-2 cells. ELISA techniques were used to measure antibodies to azurophil granule constituents (ANCA), purified myeloperoxidase (MPO-ANCA), and lactoferrin (LF-ANCA). Furthermore a qualitative spot immunoassay was used for the detection of antibodies to alpha, beta, and gamma fractions, and the nuclear fraction of neutrophils, purified proteinase 3 (PR3), MPO, enolase, lysozyme, elastase, lactoferrin, and cathepsin G. The diagnoses linked to such GS-ANA/pANCA positivity were arthritides, vasculitides, inflammatory bowel disease and chronic hepatic conditions. MPO was the main antigen recognized in the vasculitis group, but apart from that, rather limited antigen reactivity was demonstrable by these techniques, lysozyme being the most frequently recognized autoantigen in patients with arthritides. Human lymphocytes served as a suitable control substrate when distinguishing between GS-ANA/pANCA and ANA, whereas HEp-2 cells usually could not be used if both classes of antibodies were present in a sample. Furthermore, formalin-acetone fixation is not recommended for routine use.
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