ANCA pattern and LTA haplotype relationship to clinical responses to anti-TNF antibody treatment in Crohn's disease

Gastroenterology. 2001 May;120(6):1347-55. doi: 10.1053/gast.2001.23966.


Background & aims: In the clinical trial, a lower response to infliximab was observed in some patients after multiple infusions, suggesting that clinical subgroups of Crohn's disease (CD) exist based on response to anti-tumor necrosis factor (anti-TNF). The aim of this study was to characterize these subgroups further by antineutrophil cytoplasmic antibody (ANCA) pattern and TNF genotype.

Methods: Crohn's Disease Activity Index (CDAI) data from the North American patients in the clinical trial (n = 59) were evaluated as the response parameter. Speckled ANCA (sANCA) subjects were ANCA positive by ELISA with a speckling over the entire neutrophil on indirect immunofluorescence. Genotypes were determined for polymorphisms in the TNF/lymphotoxin alpha (LTA) region.

Results: Response to infliximab as median change in CDAI was placebo (least response) < perinuclear ANCA (pANCA) < not pANCA or sANCA < sANCA (greatest response) (P(overall) = 0.003; 4 weeks). The response of subjects with sANCA was significantly different from that of placebo at all time points; that of pANCA subjects was not. Homozygotes for the LTA NcoI-TNFc-aa13L-aa26 haplotype 1-1-1-1 did not respond (P(overall) = 0.007).

Conclusions: These observations suggest that sANCA may identify a CD subgroup with a better response to infliximab and that pANCA and homozygosity for the LTA 1-1-1-1 haplotype may identify subgroups with a poorer response.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Antineutrophil Cytoplasmic / blood*
  • Antibodies, Monoclonal / therapeutic use*
  • Crohn Disease / blood
  • Crohn Disease / genetics
  • Crohn Disease / therapy*
  • Haplotypes*
  • Humans
  • Infliximab
  • Lymphotoxin-alpha / genetics*
  • Microsatellite Repeats
  • Polymorphism, Genetic
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Antineutrophil Cytoplasmic
  • Antibodies, Monoclonal
  • Lymphotoxin-alpha
  • Tumor Necrosis Factor-alpha
  • Infliximab