Dendritic cell profiles in the inflamed colonic mucosa predict the responses to tumor necrosis factor alpha inhibitors in inflammatory bowel disease
, , , , , et | 26 nov. 2018
À propos de cet article
Article Category: Research Article
Publié en ligne: 26 nov. 2018
Pages: 443 - 452
Reçu: 12 sept. 2018
Accepté: 25 oct. 2018
DOI: https://doi.org/10.2478/raon-2018-0045
© 2018 Natasa Smrekar, David Drobne, Lojze M. Smid, Ivan Ferkolj, Borut Stabuc, Alojz Ihan, Andreja Natasa Kopitar, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
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Subpopulations of dendritic cells (DCs) in the inflamed inflammatory bowel disease (IBD) mucosa in responders and nonresponders before the treatment with TNFa inhibitors
| Responders | Nonresponders | p value | |
|---|---|---|---|
| 1.9 (0.4) | 1.3 (0.4) | 0.3 | |
| 9.2 (1.0) | 4.4 (0.8) | ||
| 1436 (332) | 785 (177) | 0.2 | |
| 12152 (868) | 8838 (1286) | ||
| 51.0 (3.7) | 42.5 (5.5) | 0.2 | |
| 48.8 (3.8) | 57.5 (5.5) | 0.2 |
Phenotypes of the measured dendritic cells (DC)
| Abbreviation | Phenotype | |
|---|---|---|
| Plasmacytoid DC | pDC | HLA-DR+, CD123+, CD303+, CD11c-, CD3-, CD14-, CD16-, CD19- |
| Conventional DC | cDC | HLA-DR+, CD11c+, CD123-, CD303-, CD3-, CD14-, CD16-, CD19- |
| Mature conventional DC | CD86+ DC | CD80+, CD86+, CD83+, HLA-DR+, CD11c+, CD123-, CD303-, CD3-, CD14-, CD16-, CD19- |
| Activated mature conventional DC | HLA-DR DC | HLA-DRhi, CD83+, CD80+, CD86+, CD11c+, CD123-, CD303-, CD3-, CD14-, CD16-, CD19- |
| Intestinal CD103+ DCs important in maintaining intestinal immune homeostasis | CD103+ DC | CD103+, HLA-DR+, CD11c+, CD123-, CD303-, CD3-, CD14-, CD16-, CD19- |
Subpopulations of dendritic cells (DCs) in the uninflamed and inflamed inflammatory bowel disease (IBD) mucosa before the treatment with TNFa inhibitors
| IBD-uninflamed | IBD-inflamed | p value | |
|---|---|---|---|
| 1.7 (0.2) | 1.7 (0.3) | 0.9 | |
| 4.5 (0.6) | 7.8 (0.9) | ||
| 1483 (212) | 1248 (231) | 0.53 | |
| 11965 (767) | 10918 (767) | 0.33 | |
| 57.3 (3.5) | 47.1 (3.1) | ||
| 42.3 (3.4) | 52.8 (3.2) |
Subpopulations of dendritic cells (DCs) in inflamed inflammatory bowel disease (IBD) mucosa before and after the treatment with TNFa inhibitors
| IBD-before | IBD-after | p value | |
|---|---|---|---|
| 1.7 (0.3) | 1.3 (0.2) | 0.32 | |
| 7.8 (0.9) | 4.5 (0.9) | ||
| 1248 (231) | 826 (219) | 0.29 | |
| 10918 (767) | 12141 (616) | 0.09 | |
| 47.1 (3.1) | 48.1 (4.5) | 0.86 | |
| 52.8 (3.2) | 50.7 (4.8) | 0.75 |
Clinical, biochemical and endoscopic data of the patients before and after treatment with TNFa inhibitors
| Before treatment | After treatment | |
|---|---|---|
| (week 0) | (week 12) | |
| SCCAI | 8.4 (0.9) | 3.1 (0.5) |
| CRP (mg/l) | 8.8 (2.9) | 7.8 (2.4) |
| Fecal calprotectin (mg/kg) | 351 (41.7) | 254 (58.2) |
| Endoscopic Mayo Score | 2.4 (0.1) | 1.5 (0.3) |
| HBSI | 9.5 (1.3) | 3.3 (0.8) |
| CRP (mg/l) | 17.5 (3.1) | 10.5 (3.6) |
| Fecal calprotectin (mg/kg) | 341 (40) | 209 (48) |
| SES-CD | 12.9 (1.1) | 5.5 (1.8) |
Demographic data of the patients and healthy controls enrolled in the study
| Number | Mean | |
|---|---|---|
| 40 | ||
| 16 | ||
| Female/male | 8/8 | |
| Age (years) | 38.6 | |
| (13.7) | ||
| Disease duration (years) Age at diagnosis (years) | 7.1 (6.5) 31.4 | |
| (14.5) | ||
| Smokers | 5 | |
| Ex-smokers | 3 | |
| Nonsmokers | 8 | |
| Location of Crohn’s disease | 16 | |
| I. L1 (ileal) | ||
| II. L2 (colonic) | ||
| III. L3 (ileocolonic) | ||
| IV. L4 (isolated upper disease) | ||
| Concomitant medications | 13 | |
| I. Aminosalicylates | ||
| II. Corticosteroid | ||
| III. Azathioprine | ||
| IV. Azathioprine + corticosteroids | ||
| V. None | ||
| 14 | ||
| Female/male | 8/6 | |
| Age (years) | 39.2 (12) | |
| Disease duration (years) | 5.6 (2.8) | |
| Age at diagnosis (years) | 33.5 | |
| (11.7) | ||
| Smokers | 1 | |
| Ex-smokers | 3 | |
| Nonsmokers | 10 | |
| Extent of ulcerative colitis | 14 | |
| I. E1 (proctitis) | ||
| II. E2 (left sided) | ||
| II. E3 (extensive) | ||
| Concomitant medications | 14 | |
| I. Aminosalicylates | ||
| II. Corticosteroid | ||
| III. Azathioprine | ||
| IV. Azathioprine + corticosteroids | ||
| V. None | ||
| 10 | ||
| Female | 6 | |
| Male | 4 | |
| 58.3 | ||
| Age (years) | (9.4) |
Subpopulations of dendritic cells (DC) in the inflamed inflammatory bowel disease (IBD) mucosa and the mucosa of healthy controls (HC) before the treatment with TNFa inhibitors
| IBD-inflamed | HC | p value | |
|---|---|---|---|
| 1.7 (0.3) | 0.3 (0.1) | ||
| 7.8 (0.9) | 0.5 (0.1) | ||
| 1248 (231) | 430 (43) | ||
| 10918 (767) | 11808 (711) | 0.52 | |
| 47.1 (3.1) | 66.3 (3.3) | ||
| 52.8 (3.2) | 32.1 (4.1) |
Subpopulations of dendritic cells (DCs) in the inflamed ulcerative colitis and Crohn’s disease mucosa in responders and nonresponders before the treatment with TNFa inhibitors
| Responders | Nonresponders | p value | |
|---|---|---|---|
| 2.5 (0.6) | 1.7 (0.6) | 0.9 | |
| 10.1 (1.5) | 4.7 (1.2) | ||
| 1595 (523) | 552 (40) | 0.2 | |
| 12182 (3613) | 6693 (3614) | ||
| 61.4 (7.0) | 34.8 (6.5) | ||
| 38.4 (7.1) | 65.2 (2.7) | ||
| 1.6 (0.4) | 0.9 (0.3) | 0.2 | |
| 9.7 (1.6) | 4.2 (1.0) | ||
| 1452 (434) | 1019 (335) | 0.5 | |
| 13152 (1319) | 10983 (1368) | 0.3 | |
| 50.8 (4.9) | 50.2 (9.9) | 0.9 | |
| 49.2 (4.5) | 49.8 (9.9) | 0.9 |