AUTOIMMUNITY

In fact, the term anti-nucleosome antibodies may embrace all types of antibodies that can bind nucleosomes - some occuring at higher frequency than others, indicating that the control of tolerance to components of nucleosomes vary considerably. Central problems to resolve derive from the following major questions: What do antibodies against nucleosomes recognize? Histones, histone variants, modified histones, non-histone proteins, different dsDNA structures, or diverse conformational determinants unique to the complex structure in chromatin? How will we be able to identify autoantibodies to these molecules and structures by analytical assays? In our opinion, this is not possible.

... Also, it is conceivable that autoimmunity can be triggered when a dysregulation of innate immunity occurs, activating T and B lymphocytes to react with self-components. This would imply that NK cells can play a regulatory role during adaptive immunity; indeed, innate lymphoid cells (ILCs), comprising the classical CD56+ NK cells, have a role in maintaining or alternating tissue homeostasis secreting protective and/or pro-inflammatory cytokines. In addition, NK cells display activating receptors involved in natural cytotoxicity and the activating isoforms of receptors for HLA class I that can interact with healthy host cells and induce damage without any evidence of viral infection or neoplastic-induced alteration.

There are several problems to be discussed before the anti-dsDNA antibody without further distinction can be accepted as a criterion to classify SLE. Old and contemporary knowledge make it clear that an anti-dsDNA antibody is not a unifying term. It embraces antibodies with a wide spectrum of fine molecular specificities, antibodies that are produced transiently in context of infections and persistently in context of true autoimmunity, and includes also anti-dsDNA antibodies that have the potential to bind chromatin (accessible DNA structures) and not (specificity for DNA structures that are embedded in chromatin and therefore un-accessible for the antibodies)