Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus
Lichen sclerosus is an autoimmune skin disorder that occurs in more than 1 in 300 people. The disease, which presents with hardened inflamed bumps or patches of skin, most commonly in the genital area, can result in severe scarring, resulting in impaired sexual activity, and can also be complicated by malignancy, most commonly squamous cell carcinomas. There are no biological markers or diagnostic tests to adequately diagnose this common skin disorder, and it is often misdiagnosed as signs of abuse in young children and as lichen planus in adults. Previous work on lichen sclerosus has shown the presence of specific autoantigens to extracellular matrix protein 1 (ECM1), implicating its potential involvement in the disease. ECM1 is a protein present in the epidermis and dermis, and appears to be involved in epidermal differentiation and in protein-protein interactions within the skin. John McGrath and colleagues, from St. Thomas' Hospital in London, have now characterized the portions of EMC1 that are targeted by autoantibodies from the serum of lichen sclerosus patients. They find that patient's serum contains antibodies that detect many different portions of ECM1, but were able to identify a portion of this protein (amino acids 359 to 559) that is detected by autoantibodies in the serum of nearly all disease cases. From this, they developed a novel and highly sensitive ELISA system that provides a diagnostic marker for this disease, and also gives indication of the likely clinical severity. This study provides an essential new diagnostic tool for the detection of this often debilitating skin disease, but it also presents important information on the underlying pathogenicity of the disease, in terms of the development of multiple antibodies to ECM1, a phenomenon called "epitope spreading," which is frequently seen in other autoimmune skin disorders.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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