Pathogenesis of SLE Dermatitis - A Reflection of the Process in SLE Nephritis?

Abstract

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune syndrome that may affect most organs in the body. Anti-dsDNA antibodies represent a classification criterion for SLE and are involved in lupus nephritis. Recently, the structures that bind lupus-related nephritogenic autoantibodies in vivo have been characterized by transmission electron microscopy (EM), immune-EM and co-localization immune-EM. By these methods, glomerular in vivo-bound autoantibodies were shown to co-localize with loci for binding of different experimental anti-chromatin antibodies, pointing at glomerular basement membrane-associated nucleosomes as target antigens. Lupus dermatitis has not been investigated in as much detail as lupus nephritis, but data indicate similarities between these two organ manifestations. The presence of granular antibody deposits at the dermo-epidermal junction suggests that the tissue injury is mediated by immune complexes. The deposits may be constituted by nucleosomes or chromatin and antibodies bound to them. The nucleosomes may be released locally or systemically from apoptotic cells; i.e. a process similar to that established for lupus nephritis. In this review we summarize current knowledge on immuno-pathological processes that are central in lupus nephritis, and discuss whether they may be similar to those occurring in lupus dermatitis.

Deposition of chromatin‐IgG complexes in skin of nephritic MRL‐lpr/lpr mice is associated with increased local matrix metalloprotease activities

“…One commonly encountered criterion is dermatological manifestations. The relationship between nephritis and dermatitis has been discussed, but it is not clear whether nephritic patients have a predisposition for immune complex dermatitis (4–8).…”

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

“…In harmony with this, data demonstrate that the kidney disease evolves and is maintained ( pathogenesis ), but not proven to be initiated ( etiology ) by autoimmune responses with anti-dsDNA antibodies as the central pathogenic factor ( 11 , 16 , 33 , 79 – 81 ). However, other criteria than lupus nephritis, lupus dermatitis ( 82 ), and certain cerebral affections ( 83 ), have pathogenic origins that are beyond the impact of anti-dsDNA antibodies. It may be wise to probe the term autoimmune pathogenesis with the Witebsky postulates ( 62 , 63 ) to establish a causative relationship between a specific autoimmune response and a subsequent autoimmune disease.…”

“…In SLE, anti-dsDNA antibodies are pathogenic in context of lupus nephritis ( 11 , 79 ), dermatitis ( 82 , 91 ), and in certain forms of cerebral lupus ( 27 , 83 , 92 ). Whether these pathogenic pathways are determined by cross-reaction with non-DNA structures (see Table 1 for examples) or by homologous recognition of chromatin/dsDNA exposed in e.g., glomeruli ( 11 , 93 , 94 ), skin basement membranes ( 82 ), or in the brain ( 27 ) is still not firmly established. These clinical origins of anti-dsDNA antibodies has not been seriously considered in the classification criteria, nor in the relevant literature on anti-dsDNA antibodies and SLE [discussed in ( 1 , 2 , 5 , 13 , 14 , 39 )].…”

Systemic Lupus Erythematosus: Definitions, Contexts, Conflicts, Enigmas

“…In this situation, the current state of knowledge remains vague, and does not take into account descriptions back in antiquity as being a serious cutaneous disease probably involving the kidneys as the malignant element. This is deduced from the fact that lupus-associated kidney and skin affections may have a common or similar pathogenic origin(s) ( 7 , 34 , 56 , 57 ). The same problems relate to treatment; we classify a disease phenotypically as a syndrome, but we treat the most serious organ manifestations, not the syndrome as a whole [see a discussion in Ref.…”

“…Others may serve as quasi biomarker for SLE, but occur in many other disorders as well ( 7 , 52 , 66 , 122 ). Some may serve as pathogenic factors mostly in kidneys ( 3 , 7 , 57 , 123 – 128 ) or in skin ( 56 , 123 , 129 ).…”