AUTHOR=Rekvig Ole Petter TITLE=SLE: a cognitive step forward—a synthesis of rethinking theories, causality, and ignored DNA structures JOURNAL=Frontiers in Immunology VOLUME=Volume 15 - 2024 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1393814 DOI=10.3389/fimmu.2024.1393814 ISSN=1664-3224 ABSTRACT=SLE is classified by instinctual classification criteria. A valid proclamation is that these formally accepted SLE classification criteria legitimate the syndrome as being difficult to explain, and therefore enigmatic. SLE involves scientific problems linked to etiological factors and criteria. Our insufficient understanding of the clinical condition uniformly denoted SLE depends on the still open question whether SLE is, according to classification criteria, a well-defined one disease entity, or represent a variety of overlapping indistinct syndromes. Without rational hypotheses, these problems detriment clear definition(s) of the syndrome. Why SLE is not anchored in logic, consequent, downstream interdependent and interactive inflammatory networks may rely on ignored predictive causality principles. Authoritative classification criteria do not reflect consequent causality criteria, and not unifying characterization principles such as diagnostic criteria. We need now to reconcile legendary scientific achievements to concretize delimitation of what SLE really is. Not all classified SLE syndromes are “genuine SLE”, many are theoretically “SLE-like non-SLE” syndromes. In this study, progressive theories imply imperative challenges to reconsider the fundamental impact of “The causality principle”. This may offer us logic classification and diagnostic criteria aimed to identify concise SLE syndromes as research objects. Can a system science approach solve this problem?