SPONTANEOUS INFLAMMATORY ARTHRITIS IN HLA-B27 TRANSGENIC MICE LACKING BETA(2)-MICROGLOBULIN - A MODEL OF HUMAN SPONDYLOARTHROPATHIES

Human class I major histocompatibility complex allele HLA-B27 is associated with a group of human diseases called ''spondyloarthropathies.'' Studies on transgenic rats expressing HLA-B27 and human beta(2)-microglobulin have confirmed the role of HLA-B27 in disease pathogenesis. Here we report spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta(2)-microglobulin (B27(+)beta(2)m(-/-)). In the absence of beta(2)-microglobulin, B27(+)beta(2)m(-/-) animals do not express the HLA-B27 transgene on the cell surface and have a very low level of CD8(+) T cells. Most of the B27(+)beta(2)m(-/-) male mice showed nail changes, hair loss, and swelling in paws, which leads to ankylosis. The symptoms occur only after the B27(+)beta(2)m(-/-) mice are transferred from the specific pathogen-free mouse colony. These results suggest that aberrant assembly, transport, and expression of the HLA-B27 molecule may predispose an individual for development of the disease when exposed to an appropriate environmental trigger.