Uteroglobin in the treatment of IgA mediated autoimmune disorders, screening for variants and diagnosing IgA neuropathy

摘要

A method of screening for a derivative, mimetic or variant of uteroglobin that prevents or treats an IgA mediated autoimmune disorder is disclosed, which comprises: providing a recombinant, non-human mammal having cells that normally express uteroglobin, wherein the cells have been altered to reduce or eliminate expression of uteroglobin, and predispose the mammal to develop the IgA mediated autoimmune disorder; administering to the mammal a test agent, to determine if the test agent interferes with development of the IgA mediated autoimmune disorder; and detecting the presence or absence of the IgA mediated autoimmune disorder in the mammal. Uteroglobin is useful for the prevention of IgA mediated diseases, such as IgA nephropathy, by preventing the deposition of IgA- Fibronectin immunocomplexes in tissues such as the renal glomeruli. Transgenic uteroglobin knockout animals, and animals in which uteroglobin-protein expression is reduced by antisense technology, also provide systems for studying IgA mediated diseases, and screening for appropriate treatments.