ANCA pattern and LTA haplotype relationship to clinical responses to anti-TNF antibody treatment in Crohn's disease
ANCA pattern and LTA haplotype relationship to clinical responses to anti-TNF antibody treatment in Crohn's disease
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DOI：
10.1053/gast.2001.23966
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发表时间：
2001-05-01
期刊：
影响因子：
29.4
通讯作者：
Targan, SR
中科院分区：
文献类型：
--
作者：
Taylor, KD;Plevy, SE;Targan, SR
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 Ncol 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.
