Studies of the Etiology of Crohn’s Disease Using Athymic Nude Mice

Abstract

Following injection of Crohn's disease tissue filtrates, lymphomas and hyperplastic lymph nodes developed in 16% of athymic nude (nu/nu) mice; whereas only 4% of control nude mice developed lymphadenopathy (p less than 0.025). One hundred forty coded sera from 111 patients (Crohn's disease = 36, ulcerative colitis = 28, diarrheal and other controls = 47) were assayed by indirect immunofluorescence for immunoreactivity with the lymphomas and hyperplastic lymph nodes. Coded sections were examined by two observers and scored on a 0 to 3 + scale. Fifty-four percent of the sera from patients with Crohn's disease were reactive with the Crohn's disease induced lymphoma by this assay. Eighty percent of sera from patients with symptomatic Crohn's disease were positive, whereas 22% of sera from patients in remission were positive. Sixty-six percent of sera from patients with symptomatic Crohn's disease reacted against hyperplastic lymph nodes induced by Crohn's disease filtrates. In contrast, only one control serum (from a patient with ulcerative colitis) reacted with the lymphomas or hyperplastic lymph nodes. Lymphomas induced by other means or arising spontaneously did not show immunofluorescence with Crohn's disease or control sera. Electron microscopy revealed C-type viral particles in five lymphomas induced by Crohn's disease filtrates and in one control lymphoma, but not in five hyperplastic lymph nodes and five control lymph nodes. Absorption of Crohn's disease sera with control lymphoma or with murine leukemia virus infected fibroblasts did not diminish immunoreactivity, whereas similar absorption with lymphomas induced by Crohn's disease filtrates abolished the immunofluorescence. These studies indicate that Crohn's disease tissue, when injected into athymic nude mice, induces lymphoid hyperplasia and lymphomas that contain an antigen(s) recognized by Crohn's disease sera.