Identification of the Uncultured Bacillus of Whipple’s Disease

Abstract

Whipple's disease is a systemic disorder known for 85 years to be associated with an uncultured, and therefore unidentified, bacillus. We used a molecular genetic approach to identify this organism. The bacterial 16S ribosomal RNA (rRNA) sequence was amplified directly from tissues of five unrelated patients with Whipple's disease by means of the polymerase chain reaction, first with broad-range primers and then with specific primers. We determined and analyzed the nucleotide sequence of the amplification products. A unique 1321-base bacterial 16S rRNA sequence was amplified from duodenal tissue of one patient. This sequence indicated the presence of a previously uncharacterized organism. We then detected this sequence in tissues from all 5 patients with Whipple's disease, but in none of those from 10 patients without the disorder. According to phylogenetic analysis, this bacterium is a gram-positive actinomycete that is not closely related to any known genus. We have identified the uncultured bacillus associated with Whipple's disease. The phylogenetic relations of this bacterium, its distinct morphologic characteristics, and the unusual features of the disease are sufficient grounds for naming this bacillus Tropheryma whippelii gen. nov. sp. nov. Our findings also provide a basis for a specific diagnostic test for this organism. (N Engl J Med 1992;327:293–301.), IN 1907, George Whipple reported a “hitherto undescribed disease” in a 36-year-old medical missionary with migratory polyarthritis, cough, diarrhea, malabsorption, weight loss, and mesenteric lymphadenopathy.1 He named this disease “intestinal lipodystrophy.” We now refer to it as Whipple's disease, a systemic illness, predominantly of middle-aged white men, characterized by arthralgias, diarrhea, abdominal pain, and weight loss.2 Other common findings include lymphadenopathy, fever, and increased skin pigmentation.3 The disease usually involves the gastrointestinal tract, mesentery, heart, and central nervous system; however, it can affect nearly every other organ system. The diagnosis is established when microscopical examination of the small intestine shows… © 1992, Massachusetts Medical Society. All rights reserved.