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©The Author(s) 2023.
World J Gastroenterol. Nov 14, 2023; 29(42): 5728-5750
Published online Nov 14, 2023. doi: 10.3748/wjg.v29.i42.5728
Published online Nov 14, 2023. doi: 10.3748/wjg.v29.i42.5728
Table 1 Clinical characteristics of inflammatory bowel disease patients, n (%)
CD (n = 266) | UC (n = 187) | |
Age at presentation (yr), median (IQR) | 25 (19-33) | 33 (23-43) |
Male/female (n) | 112/154 | 86/101 |
Follow-up (mo) from, median (IQR) | ||
Diagnosis1 | 143 (99-214) | 135 (84-213) |
Time of serum collection, median (IQR) | 97 (77-118) | 78 (51-102) |
Location/extent at diagnosis | ||
L1 | 58 (21.8%) | E1 30 (16.0%) |
L2 | 86 (32.3%) | E2 104 (55.6%) |
L3 | 121 (45.5%) | E3 53 (28.3%) |
L4 only | 1 (0.4%) | |
Behavior at diagnosis/last follow up | ||
B1 | 213 (80.1%)/117 (44.8%) | |
B2 | 32 (12.0%)/54 (20.7%) | |
B3 | 21 (7.9%)/90 (34.5%) | |
Perianal disease | ||
At diagnosis/last follow-up1 | 48 (18.0%)/100 (38.3%) | |
Extraintestinal manifestations | ||
PSC | 8 (3.0%) | 8 (4.3%) |
Arthritis | 49 (18.4%) | 26 (13.9%) |
Skin | 35 (13.2%) | 16 (8.6%) |
Ocular | 65 (24.4%) | 12 (6.4%) |
Smoking habits | ||
Never | 215 (80.8%) | 167 (89.3%) |
Yes | 46 (17.3%) | 18 (9.6%) |
Previous | 5 (1.9%) | 2 (1.1%) |
Familial IBD | 12 (4.4%) | 6 (3.2%) |
Frequent relapse | 52 (20.9%) | |
Cumulative exposure of medication and surgeries during follow-up | ||
Steroid use/refractory | 219 (82.3%)/30 (13.7%) | 117 (63.9%)/11 (7.6%) |
Azathioprine use | 198 (74.4%) | 70 (38.3%) |
Biological use | 112 (42.1%) | 25 (13.4%) |
Resective surgery/multiple in CD | 117 (44.8%)/ 33 (12.6%) | |
Colectomy in UC | 11 (6.0%) | |
Surgery due to perianal complication/multiple | 61 (23.4%)/33 (12.6%) |
Table 2 Prevalence of autoantibodies against chitinase 3-like 1 in inflammatory bowel disease patients
Table 3 Stability of anti-chitinase 3-like 1 autoantibodies status over time in patients with Crohn’s disease during the disease course
Serologic antibodies | (Sub)type | n | Stable negative, n (%) | Stable positive, n (%) | Negative to positive, n (%) | Positive to negative, n (%) |
aCHI3L1 | IgG | 165 | 152 (92.1) | 2 (1.2) | 2 (1.2) | 9 (5.5) |
IgA | 165 | 92 (55.8) | 39 (23.6) | 17 (10.3) | 17 (10.3) | |
sIgA | 165 | 83 (50.3) | 51 (30.9) | 14 (8.5) | 17 (1.1) |
Table 4 Association of anti-chitinase 3-like 1 autoantibodies antibody formation with clinical, serological, and genetic characteristics of Crohn’s disease at diagnosis and last follow-up
Anti-CHI3L1 | IgA | sIgA | ||
OR (95%CI) | P value | OR (95%CI) | P value | |
At diagnosis | ||||
Complicated disease behaviour | 1.86 (0.97-3.55) | 0.081 | 2.37 (1.26-4.48) | 0.009 |
Colon involvement | 6.61 (2.29-19.07) | < 0.0001 | 2.09 (1.07-4.10) | 0.038 |
ASCA IgA | 4.11 (2.24-7.55) | < 0.0001 | 4.16 (2.40-7.19) | < 0.0001 |
OMP IgA | 3.16 (1.79-5.57) | < 0.0001 | 2.64 (1.57-4.44) | < 0.0001 |
Anti-PS/PT IgA | 3.46 (1.49-8.04) | 0.005 | 2.56 (2.15-14.58) | < 0.0001 |
Anti-GP2 IgA | 4.76 (0.87-26.18) | 0.108 | 9.47 (1.12-79.52) | 0.018 |
At last visit | ||||
Frequent relapse | 2.56 (1.34-4.91) | 0.005 | 1.89 (1.00-3.56) | 0.047 |
Table 5 Univariate and multivariate Cox regression analyses evaluating the association between clinical and serologic variables and the study end-point events (complicated disease course) in Crohn’s disease patients. Subgroup analysis of B1 patients with colonic involvement is shown in the second half of the table
Development of internal penetrating and/or stenotic complication in B1 patients at diagnosis | Development of internal penetrating and/or stenotic complication in B1 patients at diagnosis with colonic involvement | ||||||||||||||
n of subjects | CP of event (%)1 | pLogRank | HR (95%CI)2 | P value2 | HR (95%CI)3 | P value3 | n of subjects | CP of event (%)1 | pLogRank | HR (95%CI)2 | P value2 | HR (95%CI)3 | P value3 | ||
Overall population | 209 | 47.5 | 160 | 44.4 | |||||||||||
Clinical factors | |||||||||||||||
Age at onset | A1 | 27 | 47.7 | 0.137 | 1.95 (0.74-5.14) | 0.175 | 26 | 47.7 | 0.095 | 4.12 (0.93-18.28) | 0.062 | 7.26 (0.94-55.89) | 0.057 | ||
A2 | 157 | 51.0 | 2.26 (0.98-5.21) | 0.055 | 118 | 46.7 | 4.20 (1.02-17.23) | 0.046 | 7.79 (1.07-56.52) | 0.042 | |||||
A3 | 25 | 25.9 | 0.152 | 16 | 19.8 | 0.137 | 0.127 | ||||||||
Gender | Male | 91 | 47.7 | 0.494 | 1.15 (0.77-1.74) | 0.495 | 69 | 44.8 | 0.489 | 1.18 (0.74-1.90) | 0.490 | 1.10 (0.68-1.79) | 0.697 | ||
Female | 118 | 47.3 | 91 | 43.9 | |||||||||||
Location | L1 + L3 | 129 | 57.3 | 0.002 | 1.98 (1.27-3.08) | 0.003 | 80 | 55.5 | 0.013 | 1.82 (1.13-2.95) | 0.014 | 1.83 (1.12-2.99) | 0.016 | ||
L2 | 80 | 34.5 | 80 | 34.5 | |||||||||||
L2 + L3 | 160 | 44.4 | 0.027 | 0.59 (0.37-0.95) | 0.029 | ||||||||||
L1 | 49 | 62.9 | |||||||||||||
Frequent relapse | No | 154 | 44.8 | 115 | 41.7 | ||||||||||
Yes | 45 | 53.3 | 0.489 | 1.18 (0.74-1.89) | 0.490 | 38 | 52.7 | 0.533 | 1.19 (0.69-2.04) | 0.534 | |||||
Antibodies against CHI3L1 | |||||||||||||||
aCHI3L1 IgG | Negative | 182 | 49.7 | 141 | 45.5 | ||||||||||
Positive | 17 | 33.9 | 0.219 | 0.57 (0.23-1.41) | 0.226 | 14 | 38.6 | 0.561 | 0.76 (0.31-1.90) | 0.562 | |||||
aCHI3L1 IgA | Negative | 145 | 44.1 | 103 | 37.4 | ||||||||||
Positive | 54 | 58.3 | 0.076 | 1.49 (0.96-2.31) | 0.078 | 52 | 58.8 | 0.028 | 1.71 (1.05-2.78) | 0.030 | 1.67 (1.02-2.71) | 0.041 | |||
aCHI3L1 sIgA | Negative | 127 | 43.7 | 92 | 36.6 | ||||||||||
Positive | 72 | 55.7 | 0.057 | 1.50 (0.99-2.29) | 0.059 | 63 | 56.6 | 0.028 | 1.70 (1.05-2.75) | 0.031 | 1.59 (0.98-2.58) | 0.061 |
Table 6 Univariate and multivariate Cox regression analyses evaluating the association between clinical and serologic variables and the study end-point events (development of perianal complications) in Crohn’s disease patients. Subgroup analysis of B1 patients with colonic involvement is shown in the second half of the table
Development of perianal penetrating complication in P0 patients at diagnosis | Development of perianal penetrating complication in P0 patients at diagnosis with colonic involvement | ||||||||||||||
n of subjects | CP of event (%)1 | pLogRank | HR (95%CI)2 | P value2 | HR (95%CI)3 | P value3 | n of subjects | CP of event (%)1 | pLogRank | HR (95%CI)2 | P value2 | HR (95%CI)3 | P value3 | ||
Overall population | 215 | 24 | 157 | 27.9 | |||||||||||
Clinical factors | |||||||||||||||
Age at onset | A1 | 25 | 34.9 | 0.011 | 5.05 (1.44-17.7) | 0.012 | 24 | 34.9 | 0.109 | 3.22 (0.92-11.31) | 0.068 | ||||
A2 | 158 | 23.9 | 2.46 (0.76-8.01) | 0.134 | 113 | 28.5 | 1.94 (0.59-6.33) | 0.274 | |||||||
A3 | 30 | 7 | 0.016 | 20 | 10.5 | 0.122 | |||||||||
Gender | Male | 90 | 23.1 | 0.584 | 0.85 (0.48-1.51) | 0.585 | 68 | 27.2 | 0.474 | 0.81 (0.45-1.45) | 0.475 | ||||
Female | 123 | 24 | 89 | 28.7 | |||||||||||
Location | L1 + L3 | 147 | 20.5 | 0.066 | 0.60 (0.35-1.04) | 0.640 | 91 | 27.1 | 0.634 | 0.87 (0.49-1.54) | 0.635 | ||||
L2 | 66 | 28.8 | 66 | 28.8 | |||||||||||
L2 + L3 | 157 | 27.9 | 0.002 | 4.25 (1.53-11.79) | 0.001 | ||||||||||
L1 | 56 | 8.9 | |||||||||||||
Frequent relapse | No | 160 | 18 | 115 | 22.3 | ||||||||||
Yes | 45 | 40.9 | 0.000 | 2.94 (1.68-5.15) | 0.000 | 33 | 44.2 | 0.001 | 2.61 (1.45-4.68) | 0.001 | |||||
Antibodies against CHI3L1 | |||||||||||||||
aCHI3L1 IgG | Negative | 187 | 22.3 | 138 | 25.0 | ||||||||||
Positive | 15 | 33.3 | 0.988 | 0.99 (0.36-2.76) | 0.988 | 12 | 37.5 | 0.933 | 0.96 (0.34-2.68) | 0.933 | |||||
aCHI3L1 IgA | Negative | 145 | 21.7 | 96 | 25.2 | ||||||||||
Positive | 57 | 25.8 | 0.624 | 1.16 (0.64-2.11) | 0.624 | 54 | 26.7 | 0.862 | 0.95 (0.51-1.75) | 0.862 | |||||
aCHI3L1 sIgA | Negative | 122 | 22.0 | 83 | 24.9 | ||||||||||
Positive | 80 | 24.7 | 0.746 | 0.91 (0.51-1.62) | 0.746 | 67 | 27.6 | 0.645 | 0.87 (0.48-1.58) | 0.645 |
Table 7 Univariate and multivariate Cox regression analyses evaluating the association between clinical and serologic variables and the study end-point events (need for resective surgery) in Crohn’s disease patients. Subgroup analysis of B1 patients with colonic involvement is shown in the second half of the table
Need for resective surgery in B1 patients at diagnosis | Need for resective surgery in B1 patients at diagnosis with colonic involvement | ||||||||||||||
n of subjects | CP of event (%)1 | pLogRank | HR (95%CI)2 | P value2 | HR (95%CI)3 | P value3 | n of subjects | CP of event (%)1 | pLogRank | HR (95%CI)2 | P value2 | HR (95%CI)3 | P value3 | ||
Overall population | 209 | 38 | 160 | 36 | |||||||||||
Clinical factors | |||||||||||||||
Age at onset | A1 | 27 | 29.1 | 0.937 | 0.94 (0.38-2.35) | 0.896 | 26 | 29.1 | 0.989 | 0.96 (0.33-2.80) | 0.945 | ||||
A2 | 157 | 39.8 | 1.06 (0.50-2.22) | 0.887 | 118 | 37 | 1.01 (0.40-2.58) | 0.980 | |||||||
A3 | 25 | 40.4 | 0.937 | 16 | 43 | 0.989 | |||||||||
Gender | Male | 91 | 34.2 | 0.958 | 0.99 (0.62-1.57) | 0.958 | 69 | 33.7 | 0.977 | 0.99 (0.59-1.66) | 0.977 | ||||
Female | 118 | 40.8 | 91 | 37.7 | |||||||||||
Location | L1 + L3 | 129 | 31.1 | 0.109 | 1.48 (0.91-2.40) | 0.112 | 80 | 41.5 | 0.174 | 1.45 (0.85-2.43) | 0.176 | ||||
L2 | 80 | 43.7 | 80 | 31.1 | |||||||||||
L2 + L3 | 160 | 50.2 | 0.382 | 0.78 (0.44-1.38) | 0.384 | ||||||||||
L1 | 49 | 36.0 | |||||||||||||
Frequent relapse | No | 154 | 36.9 | 0.950 | 115 | 35.8 | |||||||||
Yes | 45 | 38.7 | 0.98 (0.58-1.68) | 0.950 | 38 | 32.4 | 0.602 | 0.85 (0.47-1.56) | 0.852 | ||||||
Antibodies against CHI3L1 | |||||||||||||||
aCHI3L1 IgG | Negative | 182 | 38.9 | 141 | 36.4 | ||||||||||
Positive | 17 | 34.7 | 0.997 | 1.00 (0.43-2.32) | 0.997 | 14 | 39.9 | 0.623 | 1.24 (0.53-2.89) | 0.624 | |||||
aCHI3L1 IgA | Negative | 145 | 34.1 | 103 | 30.3 | ||||||||||
Positive | 54 | 48.5 | 0.246 | 1.34 (0.82-2.18) | 0.248 | 52 | 47.6 | 0.255 | 1.36 (0.80-2.29) | 0.257 | |||||
aCHI3L1 sIgA | Negative | 127 | 33.8 | 92 | 29.8 | ||||||||||
Positive | 72 | 46.3 | 0.159 | 1.40 (0.88-2.24) | 0.161 | 63 | 46.4 | 0.227 | 1.37 (0.82-2.31) | 0.230 |
Table 8 Univariate and multivariate Cox regression analyses evaluating the association between clinical and serologic variables and the study end-point events (reoperation after resection) in Crohn’s disease patients. Subgroup analysis of B1 patients with colonic involvement is shown in the second half of the table
Need for resective surgery in B1 patients with previous CD-related abdominal surgery | Need for resective surgery in B1 patients with previous CD-related abdominal surgery and colonic involvement | ||||||||||||||
n of subjects | CP of event (%)1 | pLogRank | HR (95%CI)2 | P value2 | HR (95%CI)3 | P value3 | n of subjects | CP of event (%)1 | pLogRank | HR (95%CI)2 | P value2 | HR (95%CI)3 | P value3 | ||
Overall population | 73 | 28.2 | 58 | 26.6 | |||||||||||
Clinical factors | |||||||||||||||
Age at onset | A1 | 11 | 60.2 | 0.186 | 4.47 (0.52-38.57) | 0.173 | 11 | 60.2 | 0.122 | 3.16 (0.36-27.59) | 0.298 | ||||
A2 | 54 | 23.8 | 1.94 (0.25-15.25) | 0.530 | 42 | 17.9 | 0.97 (0.12-8.13) | 0.976 | |||||||
A3 | 8 | 12.5 | 0.214 | 5 | 20.0 | 0.150 | |||||||||
Gender | Male | 32 | 29.5 | 1.03 (0.38-2.77) | 0.956 | 26 | 19.8 | 0.368 | 0.58 (0.17-1.93) | 0.374 | |||||
Female | 41 | 28.4 | 0.956 | 32 | 33.2 | ||||||||||
Location | L1 + L3 | 45 | 31.0 | 0.339 | 1.67 (0.58-4.82) | 0.345 | 30 | 29.5 | 0.454 | 1.55 (0.49-4.92) | 0.457 | ||||
L2 | 28 | 23.2 | 28 | 23.2 | |||||||||||
L2 + L3 | 58 | 26.6 | 0.430 | 0.64 (0.20-1.98) | 0.434 | ||||||||||
L1 | 15 | 35.8 | |||||||||||||
Familial IBD | No | 68 | 25.5 | 55 | 23.8 | ||||||||||
Yes | 5 | 60.0 | 0.010 | 4.59 (1.29-16.36) | 0.019 | 3 | 66.7 | 0.002 | 8.19 (1.64-40.86) | 0.010 | |||||
Frequent relapse | No | 51 | 14.9 | 40 | 9.0 | ||||||||||
Yes | 19 | 61.0 | 0.006 | 3.79 (1.36-10.55) | 0.011 | 15 | 73.3 | 0.000 | 7.94 (2.03-31.00) | 0.003 | |||||
Antibodies against CHI3L1 | |||||||||||||||
aCHI3L1 IgG | Negative | 64 | 27.3 | 51 | 23.7 | ||||||||||
Positive | 4 | 40.0 | 0.595 | 1.50 (0.34-6.69) | 0.597 | 6 | 40.0 | 0.485 | 1.72 (0.37-8.04) | 0.490 | |||||
aCHI3L1 IgA | Negative | 46 | 21.5 | 34 | 16.3 | ||||||||||
Positive | 24 | 42.1 | 0.238 | 1.83 (0.66-5.04) | 0.245 | 23 | 39.3 | 0.220 | 2.07 (0.63-6.80) | 0.230 | |||||
aCHI3L1 sIgA | Negative | 40 | 17.2 | 31 | 13.9 | ||||||||||
Positive | 30 | 46.2 | 0.052 | 2.68 (0.95-7.58) | 0.062 | 26 | 41.0 | 0.086 | 2.82 (0.82-9.68) | 0.100 |
- Citation: Sipeki N, Kovats PJ, Deutschmann C, Schierack P, Roggenbuck D, Papp M. Location-based prediction model for Crohn’s disease regarding a novel serological marker, anti-chitinase 3-like 1 autoantibodies. World J Gastroenterol 2023; 29(42): 5728-5750
- URL: https://www.wjgnet.com/1007-9327/full/v29/i42/5728.htm
- DOI: https://dx.doi.org/10.3748/wjg.v29.i42.5728