Immunoproliferative Small Intestinal Disease Associated with Campylobacter jejuni
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《新英格兰医药杂志》
To the Editor: Using a case report and retrospective series, Lecuit et al. (Jan. 15 issue)1 describe an association between Campylobacter jejuni and immunoproliferative small intestinal disease. They conclude that "C. jejuni should be added to the growing list of human pathogens responsible for immunoproliferative states." Although C. jejuni may yet be shown to cause immunoproliferative disorders, caution should be used when making the leap from association to causality.
The temporal relation between C. jejuni and immunoproliferative small intestinal disease is unknown and would be relevant in determining causality. Although C. jejuni potentially provides some "antigenic drive" for the disease, it is possible that the organism is not its initial cause. C. jejuni could simply persist in some patients with immunoproliferative small intestinal disease because of the host's illness and altered immunity. Supporting this idea are examples of persistent C. jejuni infections2,3,4,5 in other disease states characterized by immune compromise, such as disease due to human immunodeficiency virus infection and hypogammaglobulinemia. In these disorders, the persistence of C. jejuni is an outcome rather than a cause. Currently available information does not clarify whether C. jejuni is a villain or a not-so-innocent bystander.
Michael C. Peterson, M.D.
University of Utah School of Medicine
Salt Lake City, UT 84132
mike.peterson@utahtelehealth.net
References
Lecuit M, Abachin A, Martin A, et al. Immunoproliferative small intestinal disease associated with Campylobacter jejuni. N Engl J Med 2004;350:239-248.
Perlman DM, Ampel NM, Schifman RB, et al. Persistent Campylobacter jejuni infections in patients infected with the human immunodeficiency virus (HIV). Ann Intern Med 1988;108:540-546.
Bernard E, Roger PM, Carles D, Bonaldi V, Fournier JP, Dallamonica P. Diarrhea and Campylobacter infections in patients infected with the human immunodeficiency virus. J Infect Dis 1989;159:143-144.
Kaldor J, Pritchard H, Serpell A, Metcalf W. Serum antibodies in Campylobacter enteritis. J Clin Microbiol 1983;18:1-4.
Ahnen DJ, Brown WR. Campylobacter enteritis in immune-deficient patients. Ann Intern Med 1982;96:187-188.
The authors reply: We agree with Dr. Peterson that association is not proof of causation. Nevertheless, association is usually the first step in proving the microbial cause of a disease.1,2,3 With regard to the association between Helicobacter pylori and gastric lymphoma involving mucosa-associated lymphoid tissue (MALT),4 further evidence of causation is provided by the observation that eradication of H. pylori correlates with regression of the lymphoma (which is similar to what we report for C. jejuni and immunoproliferative small intestinal disease) and that H. pylori–specific T-cell clones stimulate B-cell proliferation in MALT lymphoma. With regard to the association between C. jejuni and immunoproliferative small intestinal disease, several lines of evidence presented in our article support a causal link, but to demonstrate definitively that campylobacter is the cause of immunoproliferative small intestinal disease (i.e., to fulfill Koch's postulate), several questions must be addressed. First, is C. jejuni detectable in the infected host in early stages of the disease? Second, is it possible to cultivate C. jejuni from the diseased tissue? Third, can C. jejuni trigger the disease in an animal model? Fourth, if so, can C. jejuni be isolated from the diseased animal? We are currently working on these issues.
Marc Lecuit, M.D., Ph.D.
Felipe Suarez, M.D.
Olivier Lortholary, M.D., Ph.D.
Necker–Enfants Malades University Hospital
75743 Paris, France
mlecuit@pasteur.fr
References
Relman DA, Loutit JS, Schmidt TM, Falkow S, Tompkins LS. The agent of bacillary angiomatosis: an approach to the identification of uncultured pathogens. N Engl J Med 1990;323:1573-1580.
Relman DA, Schmidt TM, MacDermott RP, Falkow S. Identification of the uncultured bacillus of Whipple's disease. N Engl J Med 1992;327:293-301.
Chang Y, Cesarman E, Pessin MS, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 1994;266:1865-1869. [Abstract/Full Text]
Parsonnet J, Hansen S, Rodriguez L, et al. Helicobacter pylori infection and gastric lymphoma. N Engl J Med 1994;330:1267-1271.
The temporal relation between C. jejuni and immunoproliferative small intestinal disease is unknown and would be relevant in determining causality. Although C. jejuni potentially provides some "antigenic drive" for the disease, it is possible that the organism is not its initial cause. C. jejuni could simply persist in some patients with immunoproliferative small intestinal disease because of the host's illness and altered immunity. Supporting this idea are examples of persistent C. jejuni infections2,3,4,5 in other disease states characterized by immune compromise, such as disease due to human immunodeficiency virus infection and hypogammaglobulinemia. In these disorders, the persistence of C. jejuni is an outcome rather than a cause. Currently available information does not clarify whether C. jejuni is a villain or a not-so-innocent bystander.
Michael C. Peterson, M.D.
University of Utah School of Medicine
Salt Lake City, UT 84132
mike.peterson@utahtelehealth.net
References
Lecuit M, Abachin A, Martin A, et al. Immunoproliferative small intestinal disease associated with Campylobacter jejuni. N Engl J Med 2004;350:239-248.
Perlman DM, Ampel NM, Schifman RB, et al. Persistent Campylobacter jejuni infections in patients infected with the human immunodeficiency virus (HIV). Ann Intern Med 1988;108:540-546.
Bernard E, Roger PM, Carles D, Bonaldi V, Fournier JP, Dallamonica P. Diarrhea and Campylobacter infections in patients infected with the human immunodeficiency virus. J Infect Dis 1989;159:143-144.
Kaldor J, Pritchard H, Serpell A, Metcalf W. Serum antibodies in Campylobacter enteritis. J Clin Microbiol 1983;18:1-4.
Ahnen DJ, Brown WR. Campylobacter enteritis in immune-deficient patients. Ann Intern Med 1982;96:187-188.
The authors reply: We agree with Dr. Peterson that association is not proof of causation. Nevertheless, association is usually the first step in proving the microbial cause of a disease.1,2,3 With regard to the association between Helicobacter pylori and gastric lymphoma involving mucosa-associated lymphoid tissue (MALT),4 further evidence of causation is provided by the observation that eradication of H. pylori correlates with regression of the lymphoma (which is similar to what we report for C. jejuni and immunoproliferative small intestinal disease) and that H. pylori–specific T-cell clones stimulate B-cell proliferation in MALT lymphoma. With regard to the association between C. jejuni and immunoproliferative small intestinal disease, several lines of evidence presented in our article support a causal link, but to demonstrate definitively that campylobacter is the cause of immunoproliferative small intestinal disease (i.e., to fulfill Koch's postulate), several questions must be addressed. First, is C. jejuni detectable in the infected host in early stages of the disease? Second, is it possible to cultivate C. jejuni from the diseased tissue? Third, can C. jejuni trigger the disease in an animal model? Fourth, if so, can C. jejuni be isolated from the diseased animal? We are currently working on these issues.
Marc Lecuit, M.D., Ph.D.
Felipe Suarez, M.D.
Olivier Lortholary, M.D., Ph.D.
Necker–Enfants Malades University Hospital
75743 Paris, France
mlecuit@pasteur.fr
References
Relman DA, Loutit JS, Schmidt TM, Falkow S, Tompkins LS. The agent of bacillary angiomatosis: an approach to the identification of uncultured pathogens. N Engl J Med 1990;323:1573-1580.
Relman DA, Schmidt TM, MacDermott RP, Falkow S. Identification of the uncultured bacillus of Whipple's disease. N Engl J Med 1992;327:293-301.
Chang Y, Cesarman E, Pessin MS, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 1994;266:1865-1869. [Abstract/Full Text]
Parsonnet J, Hansen S, Rodriguez L, et al. Helicobacter pylori infection and gastric lymphoma. N Engl J Med 1994;330:1267-1271.