Cultivation of the Bacillus of Whipple's Disease
Whipple's disease is a systemic bacterial infection characterized by fever, weight loss, diarrhea, lymphadenopathy, and polyarthritis and, occasionally, by cardiac manifestations such as myocarditis, pericarditis, and endocarditis 1 , 2 or by central nervous system involvement. 3 George Whipple...
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| Published in | The New England journal of medicine Vol. 342; no. 9; pp. 620 - 625 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Boston, MA
Massachusetts Medical Society
02.03.2000
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0028-4793 1533-4406 |
| DOI | 10.1056/NEJM200003023420903 |
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| Abstract | Whipple's disease is a systemic bacterial infection characterized by fever, weight loss, diarrhea, lymphadenopathy, and polyarthritis and, occasionally, by cardiac manifestations such as myocarditis, pericarditis, and endocarditis
1
,
2
or by central nervous system involvement.
3
George Whipple described the disease in 1907,
4
and its bacterial origins were confirmed by electron microscopy in 1961.
5
The diagnosis is usually established on microscopy by the identification in a duodenal-biopsy specimen of infiltration by large macrophages with bacteria positive for the periodic acid–Schiff (PAS) stain.
6
In 1991 Wilson et al.
7
used broad-range primers to amplify and sequence a portion of the 16S ribosomal RNA gene . . . |
|---|---|
| AbstractList | Whipple's disease is a systemic bacterial infection, but to date no isolate of the bacterium has been established in subculture, and no strain of this bacterium has been available for study.BACKGROUNDWhipple's disease is a systemic bacterial infection, but to date no isolate of the bacterium has been established in subculture, and no strain of this bacterium has been available for study.Using specimens from the aortic [corrected] valve of a patient with endocarditis due to Whipple's disease, we isolated and propagated a bacterium by inoculation in a human fibroblast cell line (HEL) with the use of a shell-vial assay. We tested serum samples from our patient, other patients with Whipple's disease, and control subjects for the presence of antibodies to this bacterium.METHODSUsing specimens from the aortic [corrected] valve of a patient with endocarditis due to Whipple's disease, we isolated and propagated a bacterium by inoculation in a human fibroblast cell line (HEL) with the use of a shell-vial assay. We tested serum samples from our patient, other patients with Whipple's disease, and control subjects for the presence of antibodies to this bacterium.The bacterium of Whipple's disease was grown successfully in HEL cells, and we established subcultures of the isolate. Indirect immunofluorescence assays showed that the patient's serum reacted specifically against the bacterium. Seven of 9 serum samples from patients with Whipple's disease had IgM antibody titers of 1:50 or more, as compared with 3 of 40 samples from the control subjects (P<0.001). Polyclonal antibodies against the bacterium were generated by inoculation of the microorganism into mice and were used to detect bacteria in the excised cardiac tissue from our patient on immunohistochemical analysis. The 16S ribosomal RNA gene of the cultured bacterium was identical to the sequence for Tropheryma whippelii identified previously in tissue samples from patients with Whipple's disease. The strain we have grown is available in the French National Collection.RESULTSThe bacterium of Whipple's disease was grown successfully in HEL cells, and we established subcultures of the isolate. Indirect immunofluorescence assays showed that the patient's serum reacted specifically against the bacterium. Seven of 9 serum samples from patients with Whipple's disease had IgM antibody titers of 1:50 or more, as compared with 3 of 40 samples from the control subjects (P<0.001). Polyclonal antibodies against the bacterium were generated by inoculation of the microorganism into mice and were used to detect bacteria in the excised cardiac tissue from our patient on immunohistochemical analysis. The 16S ribosomal RNA gene of the cultured bacterium was identical to the sequence for Tropheryma whippelii identified previously in tissue samples from patients with Whipple's disease. The strain we have grown is available in the French National Collection.We cultivated the bacterium of Whipple's disease, detected specific antibodies in tissue from the source patient, and generated specific antibodies in mice to be used in the immunodetection of the microorganism in tissues. The development of a serologic test for Whipple's disease may now be possible.CONCLUSIONSWe cultivated the bacterium of Whipple's disease, detected specific antibodies in tissue from the source patient, and generated specific antibodies in mice to be used in the immunodetection of the microorganism in tissues. The development of a serologic test for Whipple's disease may now be possible. Whipple's disease is a systemic bacterial infection characterized by fever, weight loss, diarrhea, lymphadenopathy, and polyarthritis and, occasionally, by cardiac manifestations such as myocarditis, pericarditis, and endocarditis 1 , 2 or by central nervous system involvement. 3 George Whipple described the disease in 1907, 4 and its bacterial origins were confirmed by electron microscopy in 1961. 5 The diagnosis is usually established on microscopy by the identification in a duodenal-biopsy specimen of infiltration by large macrophages with bacteria positive for the periodic acid–Schiff (PAS) stain. 6 In 1991 Wilson et al. 7 used broad-range primers to amplify and sequence a portion of the 16S ribosomal RNA gene . . . Whipple's disease is a systemic bacterial infection, but to date no isolate of the bacterium has been established in subculture, and no strain of this bacterium has been available for study. Using specimens from the mitral valve of a patient with endocarditis due to Whipple's disease, we isolated and propagated a bacterium by inoculation in a human fibroblast cell line (HEL) with the use of a shell-vial assay. We tested serum samples from our patient, other patients with Whipple's disease, and control subjects for the presence of antibodies to this bacterium. The bacterium of Whipple's disease was grown successfully in HEL cells, and we established subcultures of the isolate. Indirect immunofluorescence assays showed that the patient's serum reacted specifically against the bacterium. Seven of 9 serum samples from patients with Whipple's disease had IgM antibody titers of 1:50 or more, as compared with 3 of 40 samples from the control subjects (P<0.001). Polyclonal antibodies against the bacterium were generated by inoculation of the microorganism into mice and were used to detect bacteria in the excised cardiac tissue from our patient on immunohistochemical analysis. The 16S ribosomal RNA gene of the cultured bacterium was identical to the sequence for Tropheryma whippelii identified previously in tissue samples from patients with Whipple's disease. The strain we have grown is available in the French National Collection. We cultivated the bacterium of Whipple's disease, detected specific antibodies in tissue from the source patient, and generated specific antibodies in mice to be used in the immunodetection of the microorganism in tissues. The development of a serologic test for Whipple's disease may now be possible. A study reports the successful isolation and establishment of a strain of the bacterium for Whipple's disease obtained from the mitral valve of a patient with blood-culture-negative endocarditis. The development of a serologic test for Whipple's disease may now be possible. Whipple's disease is a systemic bacterial infection, but to date no isolate of the bacterium has been established in subculture, and no strain of this bacterium has been available for study. Using specimens from the aortic [corrected] valve of a patient with endocarditis due to Whipple's disease, we isolated and propagated a bacterium by inoculation in a human fibroblast cell line (HEL) with the use of a shell-vial assay. We tested serum samples from our patient, other patients with Whipple's disease, and control subjects for the presence of antibodies to this bacterium. The bacterium of Whipple's disease was grown successfully in HEL cells, and we established subcultures of the isolate. Indirect immunofluorescence assays showed that the patient's serum reacted specifically against the bacterium. Seven of 9 serum samples from patients with Whipple's disease had IgM antibody titers of 1:50 or more, as compared with 3 of 40 samples from the control subjects (P<0.001). Polyclonal antibodies against the bacterium were generated by inoculation of the microorganism into mice and were used to detect bacteria in the excised cardiac tissue from our patient on immunohistochemical analysis. The 16S ribosomal RNA gene of the cultured bacterium was identical to the sequence for Tropheryma whippelii identified previously in tissue samples from patients with Whipple's disease. The strain we have grown is available in the French National Collection. We cultivated the bacterium of Whipple's disease, detected specific antibodies in tissue from the source patient, and generated specific antibodies in mice to be used in the immunodetection of the microorganism in tissues. The development of a serologic test for Whipple's disease may now be possible. |
| Author | Fournier, Pierre E Piette, Jean-Charles Vital-Durand, Denis Vandenesch, François Marrie, Tom J Birg, Marie L Scola, Bernard La Lepidi, Hubert Enea, Maryse Roux, Veronique Raoult, Didier |
| Author_xml | – sequence: 1 givenname: Didier surname: Raoult fullname: Raoult, Didier – sequence: 2 givenname: Marie L surname: Birg fullname: Birg, Marie L – sequence: 3 givenname: Bernard La surname: Scola fullname: Scola, Bernard La – sequence: 4 givenname: Pierre E surname: Fournier fullname: Fournier, Pierre E – sequence: 5 givenname: Maryse surname: Enea fullname: Enea, Maryse – sequence: 6 givenname: Hubert surname: Lepidi fullname: Lepidi, Hubert – sequence: 7 givenname: Veronique surname: Roux fullname: Roux, Veronique – sequence: 8 givenname: Jean-Charles surname: Piette fullname: Piette, Jean-Charles – sequence: 9 givenname: François surname: Vandenesch fullname: Vandenesch, François – sequence: 10 givenname: Denis surname: Vital-Durand fullname: Vital-Durand, Denis – sequence: 11 givenname: Tom J surname: Marrie fullname: Marrie, Tom J |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1280782$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/10699161$$D View this record in MEDLINE/PubMed |
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| CODEN | NEJMAG |
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| Cites_doi | 10.1128/JCM.37.6.1899-1905.1999 10.1097/00005792-199705000-00003 10.1099/00207713-49-4-1701 10.1128/JCM.37.3.785-787.1999 10.1086/513631 10.1128/JCM.34.11.2722-2727.1996 10.1097/00005792-197005000-00001 10.1086/313477 10.1038/nm0396-342 10.1056/NEJM199207303270501 10.3181/00379727-72-17388 10.1056/NEJM198410043111407 10.1086/514100 10.1056/NEJM198110223051708 10.7326/0003-4819-126-7-199704010-00004 10.1128/JCM.36.10.2847-2852.1998 10.1084/jem.112.3.445 10.1099/00207713-44-1-174 10.1128/CMR.9.3.382 10.1016/0140-6736(91)90545-Z 10.3181/00379727-103-25637 10.1056/NEJM199012063232303 10.1086/514089 10.1136/thx.33.4.500 10.3109/10520296409061219 |
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| Keywords | Human Exploration Infection Case study Microbiological investigation Intestinal malabsorption Pathogen strain Bacteriosis Digestive diseases Intestinal disease Isolation Whipple disease Culture |
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| SubjectTerms | Actinobacteria - genetics Actinobacteria - growth & development Actinobacteria - immunology Actinobacteria - isolation & purification Adult Animals Antibodies, Bacterial - blood Bacteria Bacterial diseases Bacterial diseases of the digestive system and abdomen Bacterial infections Bacteriological Techniques Biological and medical sciences Cardiology Cell culture Cell Line Endocarditis, Bacterial - microbiology Fluorescent Antibody Technique, Direct Human bacterial diseases Humans Immunoglobulin G - blood Immunoglobulin M - blood Infectious diseases Male Medical sciences Mice Mice, Inbred BALB C Microscopy Mitral Valve - microbiology Tropheryma whippelii Ultrasonic imaging Whipple Disease - diagnosis Whipple Disease - immunology Whipple Disease - microbiology |
| Title | Cultivation of the Bacillus of Whipple's Disease |
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