Kupffer cell staining by an HFE-specific monoclonal antibody: implicationsfor hereditary haemochromatosis

Hereditary haemochromatosis is an inherited disorder of iron absorption tha t leads to excessive iron storage in the liver and other organs. A candidat e disease gene HFE has been identified that encodes a novel MHC class I lik e protein. We report the development of a monoclonal antibody (HFE-JB1) spe cific for recombinant refolded HFE protein. The antibody immunoprecipitates a 49 kD protein from the cell line U937, a histiocytic lymphoma. It binds HFE but does not recognize other recombinant non-classic MHC class I protei ns (HLA-E, F and G), nor does it react with a variety of recombinant classi c class I MHC molecules. COS cells transfected with HFE in culture are stai ned specifically The immunohistochemical staining pattern in human tissues is unique and can be defined as a subset of the transferrin receptor positi ve cells. In the liver HFE protein was shown to be present on Kupffer cells and endothelium (sinusoidal lining cells), but absent from the parenchyma. Kupffer cells from an untreated C282Y HH patient failed to stain with the antibody. In the normal gut scattered cells in the crypts are stained. HFE was also present on capillary endothelium in the brain (a site of high leve ls of transferrin receptor) and on scattered cells in the cerebellum and co rtex. These results raise interesting questions concerning the function of HFE in the control of body iron content and distribution.