IMMUNOPATHOLOGIC CHARACTERIZATION OF TYPHLITIS AND COLITIS IN JUVENILE HLA-B27 TRANSGENIC RATS

Adult HLA-B27 transgenic rats carrying high copy numbers of human HLA-B27 and beta(2)-microglobulin genes spontaneously develop spondyloarthropathy and enterocolitis comparable to human HLA-B27-associated disease. In this investigation, juvenile HLA-27 transgenic rats were utilized to study incipient immunopathologic events in HLA-B27-associated gastrointestinal inflammation. Flow cytometric analysis of peripheral lymphocytes demonstrated distinctive differences in HLA-B27 protein expression and prompted the division of these transgenic rodents into 2 groups: HLA-B27(hi) and HLA-B27(lo). The HLA-B27(hi) group, which represented 60% of the rats (aged 8-12 weeks) had inflammation in the colon, anorectal junction and cecum but spaced the small intestine. Inflammation coexisted with high levels of surface HLA-B27 expression by hematopoietically derived cells as determined by immunofluorescence staining and flow cytometric analysis of intestinal lymphocytes. Inflammation, which was most intense in the cecum and anorectal junction, was characterized by mixed cellular infiltrate, crypt hyperplasia, transepithelial migration of neutrophils and a reduction in goblet cells. T lymphocytes, particularly CD4+ T cells, predominated over other lymphocytes in the inflammatory infiltrate of the lamina propria. Conversely, no inflammation was evident at any level of the gastrointestinal tract in the HLA-B27(lo) group (8 weeks of age) which constituted 40% of the juvenile transgenic rats. These animals all expressed low lever of HLA-B27 protein. Collectively, these data indicate that HLA-B27 protein expression increases dramatically from 8 to 12 weeks of age and that the level of protein expression and intestinal inflammation are interrelated. These associated gastrointestinal events occur during puberty and thus we speculate that the high level of protein expression may be hormonally mediated.