Autoimmunity and SLE: Factual and Semantic Evidence-Based Critical Analyses of Definitions, Etiology, and Pathogenesis

Abstract

One cannot discuss anti-dsDNA antibodies and lupus nephritis without discussing the nature of Systemic lupus erythematosus (SLE). SLE is insistently described as a prototype autoimmune syndrome, with anti-dsDNA antibodies as a central biomarker and a pathogenic factor. The two entities, “SLE” and “The Anti-dsDNA Antibody,” have been linked in previous and contemporary studies although serious criticism to this mutual linkage have been raised: Anti-dsDNA antibodies were first described in bacterial infections and not in SLE; later in SLE, viral and parasitic infections and in malignancies. An increasing number of studies on classification criteria for SLE have been published in the aftermath of the canonical 1982 American College of Rheumatology SLE classification sets of criteria. Considering these studies, it is surprising to observe a nearby complete absence of fundamental critical/theoretical discussions aimed to explain how and why the classification criteria are linked in context of etiology, pathogenicity, or biology. This study is an attempt to prioritize critical comments on the contemporary definition and classification of SLE and of anti-dsDNA antibodies in context of lupus nephritis. Epidemiology, etiology, pathogenesis, and measures of therapy efficacy are implemented as problems in the present discussion. In order to understand whether or not disparate clinical SLE phenotypes are useful to determine its basic biological processes accounting for the syndrome is problematic. A central problem is discussed on whether the clinical role of anti-dsDNA antibodies from principal reasons can be accepted as a biomarker for SLE without clarifying what we define as an anti-dsDNA antibody, and in which biologic contexts the antibodies appear. In sum, this study is an attempt to bring to the forum critical comments on the contemporary definition and classification of SLE, lupus nephritis and anti-dsDNA antibodies. Four concise hypotheses are suggested for future science at the end of this analytical study.

The role of epigenetics in childhood autoimmune diseases with hematological manifestations

“…It is a rheumatic disease characterized by autoantibodies directed against self‐antigens, immune complex formation, and immune dysregulation, with resultant damage to essentially any organ. Hematological manifestations are common in SLE, both at diagnosis and during the course of the disease, the most common of which are leukopenia, thrombocytopenia, lymphadenopathy, and/or splenomegaly 11,37 . Many recent studies have documented the importance of dysregulation of the T‐cell and B‐cell response as a trigger in SLE 38 .…”

“…Hematological manifestations are common in SLE, both at diagnosis and during the course of the disease, the most common of which are leukopenia, thrombocytopenia, lymphadenopathy, and/or splenomegaly. 11 , 37 Many recent studies have documented the importance of dysregulation of the T‐cell and B‐cell response as a trigger in SLE. 38 Abnormal cell responses in SLE include downregulation of the Th1 and Treg cells, upregulation of Th17 cells, decreased cytotoxicity of CD8 + T cells, and increased B‐cell activation and autoantibody production.…”

Investigating the Molecular Mechanism of Xijiao Dihuang Decoction for the Treatment of SLE Based on Network Pharmacology and Molecular Docking Analysis

“…In recent years, the prevalence of SLE has shown an upward trend [ 2 ]. The etiology and pathogenesis of SLE are not yet clear, which may be related to multiple factors such as genetic factors, environmental factors, and estrogen levels [ 3 – 5 ]. The treatment of SLE is still a difficult problem in the medical field, and modern medicine mostly uses glucocorticoids and immunosuppressive drugs [ 6 ], which may produce some side effects [ 7 ].…”

Anti-double stranded DNA antibodies: A rational diagnostic approach in limited-resource settings

“…Despite controversies, anti-dsDNA Abs are a highly valuable biomarker and a pathogenic factor of systemic lupus erythematosus (SLE) [ [2] , [3] , [4] ]. They are considered as excellent indicators of disease activity, with their levels increasing concomitantly with the flare-ups of SLE, especially in lupus nephritis, and decreasing in response to treatment [ 2 ].…”