Volume 120, Issue 6, Pages (May 2001)

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Volume 120, Issue 6, Pages 1347-1355 (May 2001) ANCA pattern and LTA haplotype relationship to clinical responses to anti-TNF antibody treatment in Crohn's disease  Kent D. Taylor, Huiying Yang, Carol J. Landers, Jerome I. Rotter, Stephan R. Targan  Gastroenterology  Volume 120, Issue 6, Pages 1347-1355 (May 2001) DOI: 10.1053/gast.2001.23966 Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 1 sANCA pattern. IIF was performed as described in Methods. Gastroenterology 2001 120, 1347-1355DOI: (10.1053/gast.2001.23966) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 2 Location of polymorphisms in the TNF region used in this study. Diagram showing the positions of the TNF microsatellites (TNFa,b,c,d,e14-19,29), the TNF promoter SNPs −238 and −308, and the LTA SNPs aa26, aa13L, and NcoI. (A) Location of the TNF region with respect to major landmarks of the MHC.16 Numbers refer to the position in megabases on the standard MHC contig. (B) Genomic region spanning LST1 to LTA. Exon/intron structure is approximate. Locations are based on Genbank accession AF129756.15 Scale refers to the kilobasepair position in this accession. (C) Genomic region spanning the aa26 polymorphism to the NcoI polymorphism of the LTA gene. Scale refers to the base pair position in Genbank accession AF129756. Gene symbols: LST1, lymphocyte specific transcript 1, human homologue of the mouse B144 gene, locus link 7940; LTB, lymphotoxin β, also known as TNF C, LT-β, TNF superfamily, member 3, or locus link 4050; TNF, TNF-α, TNF superfamily member 2, or locus link 7124; LTA, lymphotoxin α, also known as LT-α, TNF-β, TNF superfamily member 1, or locus link 4049. Locus link information is available online from the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov). Gastroenterology 2001 120, 1347-1355DOI: (10.1053/gast.2001.23966) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 3 ANCA status and response to infliximab. Patients were from the North American cohort (n = 75). Determination of response rate, median change in CDAI and IBDQ, and ANCA status are described in Methods. ANCA status was not available for 1 patient treated with infliximab. Statistical comparisons were made as described in Methods. sANCA, IIF with a speckled pattern; pANCA, IIF with perinuclear staining; other, not sANCA or pANCA. Clinical endpoints were evaluated at (A) 4 weeks, (B) 8 weeks, and (C) 12 weeks. Gastroenterology 2001 120, 1347-1355DOI: (10.1053/gast.2001.23966) Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 4 LTA haplotype and response to infliximab. LTA haplotype NcoI-TNFc-aa13-aa26 1-1-1-1 is defined in Methods and illustrated in Figure 2. Genotyping and determination of response rate and the median change in CDAI and IBDQ are described in Methods. X stands for any other haplotype besides 1-1-1-1. All patients were treated with infliximab. (A) LTA haplotype and response rate to infliximab. Clinical endpoint determined at 4 weeks. (B) LTA haplotype and median change in CDAI. Median change in CDAI was determined for each genotype group as shown. (C) LTA haplotype and median change in IBDQ. Median change in IBDQ was determined for each genotype as shown. Statistical comparisons were made as described in Methods. Gastroenterology 2001 120, 1347-1355DOI: (10.1053/gast.2001.23966) Copyright © 2001 American Gastroenterological Association Terms and Conditions