Combining TNFSF15 and ASCA IgA can be used as a predictor for the  stenosis/perforating phenotype of Crohn's disease.
OBJECTIVE
Focusing on TNFSF15 instead of NOD2, we set out to evaluate whether combining serologic and genetic markers could distinguish between Crohn’s disease (CD) and ulcerative colitis (UC), and whether they could be used to stratify the disease behavior of Taiwanese CD patients.


METHODS
Clinical information, serum isolation, and DNA were collected after obtaining informed consent. The serological markers were analyzed by ELISA kits and the genetic analysis for TNFSF15 single-nucleotide polymorphisms (SNPs) by Sequenom. Statistic analyses were conducted by SAS 9.2 (Cary, NC, USA).


RESULTS
This study included 108 patients (55 CD, 53 UC) and 60 healthy controls. An initial low positive rate and low sensitivity for the serological markers led us to reset the cut-off values. This reset cut-off for ASCA IgA yielded a sensitivity of 0.291 and specificity of 0.925 for differentiating CD from UC patients. The reset cut-off value for p-ANCA (anti-MPO) had a sensitivity of 0.461 and a specificity of 0.817 for differentiating inflammatory bowel disease patients from healthy controls. Among the TNFSF15 SNPs, rs4263839 associated with CD in Taiwan (P = 0.005), haplotype analysis did not increase the association. Combining the genetic marker TNFSF15 (rs4263839) and serological marker ASCA IgA increased the area under the curve from 0.61 to 0.70 for predicting stenosis/perforating phenotype, compared to ASCA IgA alone.


CONCLUSIONS
Serological markers need to be tested and tailored to different countries/ethnicities. Combining the genetic marker TNFSF15 with ASCA IgA increased the power of predicting stenosis/perforating phenotype in CD patients with TNFSF15 but not with a NOD2 genetic background.
Chien-Chih
CC
Tung
Jau-Min
JM
Wong
Wen-Chung
WC
Lee
Heng-Hsiu
HH
Liu
Chin-Hao
CH
Chang
Ming-Chu
MC
Chang
Yu-Ting
YT
Chang
Ming-Jium
MJ
Shieh
Cheng-Yi
CY
Wang
Shu-Chen
SC
Wei
D000293:Adolescent; D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005819:Genetic Markers; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012441:Saccharomyces cerevisiae / Q000276:immunology*; D013624:Taiwan; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics*; D055815:Young Adult
D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D005819:Genetic Markers; D007070:Immunoglobulin A; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15