title: Cutaneous lupus erythematosus: clinical aspects and molecular pathogenesis.
abstract: Lupus erythematosus (LE) is an autoimmune disease with diverse clinical manifestations ranging from limited cutaneous (CLE) to potentially life-threatening systemic disease (SLE). Susceptibility to LE arises from genetic variation in multiple loci, and disease activity is provoked by exogenous or endogenous trigger(s), the best characterized of which is exposure to ultraviolet radiation (UVR). Amongst patients with LE, a cluster of photosensitive subjects with cutaneous lesions and positivity for anti-Ro/SSA autoantibodies have been described. The Ro52 antigen belongs to the tripartite motif protein family and has E3 ligase activity. New data reveal that Ro52 ubiquitinates interferon regulatory factors and modulates their transcriptional activity, indicating an important role for Ro52 in inflammation as a negative feedback regulator. Our findings indicate that UVR exposure induces upregulation of Ro52 in the CLE target cell, the keratinocyte, and that Ro52 is upregulated in spontaneous and UVR-induced CLE lesions. Recently described functional analysis of Ro52-deficient mice revealed that loss of Ro52 results in uncontrolled inflammation in response to minor skin injury leading to an LE-like condition. In summary, emerging data suggest that abnormal function or regulation of Ro52 contributes to the pathogenesis of UVR-induced CLE in genetically susceptible individuals. Ro52 may thus be an interesting therapeutic target, as its activation could contribute to downregulation of the chronic inflammatory process in LE. Here, we review the available data on the pathogenesis of CLE and, in particular, the role of the Ro52 autoantigen.
authors: Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital in Solna, Stockholm, Sweden.
authors: V
authors: V
authors: Oke
authors: M
authors: M
authors: Wahren-Herlenius
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D006801:Humans; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008178:Lupus Erythematosus, Cutaneous / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000473:pathology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens