Immunoproliferative small intestinal disease associated with Campylobacter jejuni

N Engl J Med. 2004 Jan 15;350(3):239-48. doi: 10.1056/NEJMoa031887.


Background: Immunoproliferative small intestinal disease (also known as alpha chain disease) is a form of lymphoma that arises in small intestinal mucosa-associated lymphoid tissue (MALT) and is associated with the expression of a monotypic truncated immunoglobulin alpha heavy chain without an associated light chain. Early-stage disease responds to antibiotics, suggesting a bacterial origin. We attempted to identify a causative agent.

Methods: We performed polymerase chain reaction (PCR), DNA sequencing, fluorescence in situ hybridization, and immunohistochemical studies on intestinal-biopsy specimens from a series of patients with immunoproliferative small intestinal disease.

Results: Analysis of frozen intestinal tissue obtained from an index patient with immunoproliferative small intestinal disease who had a dramatic response to antibiotics revealed the presence of Campylobacter jejuni. A follow-up retrospective analysis of archival intestinal-biopsy specimens disclosed campylobacter species in four of six additional patients with immunoproliferative small intestinal disease.

Conclusions: These results indicate that campylobacter and immunoproliferative small intestinal disease are associated and that C. jejuni should be added to the growing list of human pathogens responsible for immunoproliferative states.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents
  • Anti-Ulcer Agents / therapeutic use
  • Campylobacter Infections
  • Campylobacter jejuni / genetics
  • Campylobacter jejuni / isolation & purification*
  • DNA, Bacterial / analysis
  • Drug Therapy, Combination / therapeutic use
  • Female
  • Genes, Immunoglobulin
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin Fragments / analysis
  • Immunoglobulin Fragments / genetics
  • Immunohistochemistry
  • Immunoproliferative Small Intestinal Disease / drug therapy
  • Immunoproliferative Small Intestinal Disease / microbiology*
  • Immunoproliferative Small Intestinal Disease / pathology
  • In Situ Hybridization, Fluorescence
  • Intestine, Small / immunology
  • Intestine, Small / microbiology
  • Intestine, Small / pathology
  • Middle Aged
  • Omeprazole / therapeutic use
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA


  • Anti-Bacterial Agents
  • Anti-Ulcer Agents
  • DNA, Bacterial
  • Immunoglobulin A
  • Immunoglobulin Fragments
  • Omeprazole