This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schneemann, M.
Right arrow Articles by Cockerill, F. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schneemann, M.
Right arrow Articles by Cockerill, F. R., III

 Previous Article  |  Next Article 

Journal of Clinical Microbiology, October 2005, p. 5414, Vol. 43, No. 10
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.10.5414.2005

LETTER TO THE EDITOR

Whipple's DNA Is Not Whipple's Disease


arrow
LETTER
 
Sloan et al. report a real-time PCR method using the hsp65 gene of Tropheryma whipplei for a target sequence as a new and rapid diagnostic test for Whipple's disease (7). We and others have already published real-time PCR-based methods for the detection of T. whipplei DNA using 16 rRNA or other gene target sequences (2-4, 9).

The problem with diagnosing Whipple's disease, however, lies beyond the sensitivity or speed of the PCR test used. DNA of T. whipplei has repeatedly been shown to be present in human samples from healthy people without Whipple's disease (8, 9). In our study, 4 out of 10 healthy individuals harbored DNA of T. whipplei in gingival plaque (9). Whipple's disease is thought to be caused by a not-yet-characterized immune defect rendering the host prone to the bacterium T. whipplei. The hallmark of Whipple's disease is the histopathological finding of macrophages containing diastase-resistant p-aminosalicylic acid (PAS)-positive material, which are T. whipplei bacteria or partly digested remnants thereof. In patients with Whipple's disease, tissue macrophages are unable to kill and clear T. whipplei. This deficiency in killing then causes Whipple's disease (5). The postulated immune defect can be simulated in vitro by the deactivation of human macrophages by interleukin-4; the human macrophages are then unable to kill T. whipplei (6). Therefore, histopathologic examination and staining of tissue biopsies (PAS/diastase-PAS staining) are essential for the diagnosis of Whipple's disease. The mere presence of DNA of T. whipplei, as demonstrated by PCR, without a demonstration of the macrophages harboring it, is not Whipple's disease. It remains doubtful whether clinical syndromes which are nonspecific (such as polyarthritis) plus demonstration of DNA of T. whipplei alone, without demonstration of PAS-positive macrophages (i.e., immunodeficient macrophages unable to digest T. whipplei), qualify as some kind of forme fruste of Whipple's disease (1).


arrow
REFERENCES
 
    1
  1. Bruhlmann, P., B. A. Michel, and M. Altwegg. 2000. Diagnosis and therapy monitoring of Whipple's arthritis by polymerase chain reaction. Rheumatology (Oxford) 39:1427-1428.
    2. 2
  2. Fenollar, F., P.-E. Fournier, D. Raoult, R. Gérolami, H. Lepidi, and C. Poyart. 2002. Quantitative detection of Tropheryma whipplei DNA by real-time PCR. J. Clin. Microbiol. 40:1119-1120.[Free Full Text]
    3. 3
  3. Fenollar, F., P.-E. Fournier, C. Robert, and D. Raoult. 2004. Use of genome selected repeated sequences increases the sensitivity of PCR detection of Tropheryma whipplei. J. Clin. Microbiol. 42:401-403.[Abstract/Free Full Text]
    4. 4
  4. Maibach, R. C., and M. Altwegg. 2003. Cloning and sequencing an unknown gene of Tropheryma whipplei and development of two LightCycler PCR assays. Diagn. Microbiol. Infect. Dis. 46:181-187.[Medline]
    5. 5
  5. Marth, T., and D. Raoult. 2003. Whipple's disease. Lancet 361:239-246.[CrossRef][Medline]
    6. 6
  6. Schoedon, G., D. Goldenberger, R. Forrer, A. Gunz, F. Dutly, M. Hochli, M. Altwegg, and A. Schaffner. 1997. Deactivation of macrophages with interleukin-4 is the key to the isolation of Tropheryma whippelii [sic]. J. Infect. Dis. 176:672-677.[Medline]
    7. 7
  7. Sloan, L. M., J. E. Rosenblatt, and F. R. Cockerill III. 2005. Detection of Tropheryma whipplei DNA in clinical specimens by LightCycler real-time PCR. J. Clin. Microbiol. 43:3516-3518.[Abstract/Free Full Text]
    8. 8
  8. Street, S., H. D. Donoghue, and G. H. Neild. 1999. Tropheryma whippelii [sic] DNA in saliva of healthy people. Lancet 354:1178-1179.[CrossRef][Medline]
    9. 9
  9. Zinkernagel, A. S., R. Gmur, L. Fenner, A. Schaffner, G. Schoedon, and M. Schneemann. 2003. Marginal and subgingival plaque—a natural habitat of Tropheryma whipplei? Infection 31:86-91.[CrossRef][Medline]
Markus Schneemann*
Gabriele Schoedon
Research Unit Medical Clinic B
University Hospital
Rämistrasse 100
8091 Zürich, Switzerland

* Phone: 41 44 255 4089, Fax: 41 44 255 4445, E-mail: markus.schneemann{at}usz.ch


Authors' Reply


arrow
LETTER 
 
We agree with Schneemann and colleagues that a positive PCR result for T. whipplei in human specimens should be interpreted in the context of clinical signs and symptoms of the patient and corroborating laboratory data, including the results for PAS staining of specimens.

As the title of our article summarizes, the intent of our study was to compare a new PCR method, real-time PCR, to conventional PCR for detecting T. whipplei in human specimens. As we state in the Discussion, the real-time PCR method was comparable in accuracy to the conventional PCR method, but the real-time PCR method was much faster and much easier to perform. Our intent was not to prove the clinical significance of a positive PCR result for T. whipplei in human specimens.

Lynne M. Sloan
Jon E. Rosenblatt
Franklin R. Cockerill III*
Division of Clinical Microbiology
Department of Laboratory Medicine  and Pathology
Mayo Clinic-Mayo Foundation
200 First St., SW
Rochester, MN 55905

* Phone: (507) 284-3697
Fax: (507) 284-4272
E-mail: cockerill.franklin{at}mayo.edu

Journal of Clinical Microbiology, October 2005, p. 5414, Vol. 43, No. 10
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.10.5414.2005





This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schneemann, M.
Right arrow Articles by Cockerill, F. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schneemann, M.
Right arrow Articles by Cockerill, F. R., III

Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»