Isotype-specific Antibody Responses to Mycobacterium avium paratuberculosis Antigens Are Associated With the Use of Biologic Therapy in Inflammatory Bowel Disease
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| Title: | Isotype-specific Antibody Responses to Mycobacterium avium paratuberculosis Antigens Are Associated With the Use of Biologic Therapy in Inflammatory Bowel Disease |
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| Authors: | van der Sloot, Kimberley W.J., Voskuil, Michiel D., Blokzijl, Tjasso, Dinkla, A., Ravesloot, L., Visschedijk, Martijn C., van Dullemen, Hendrik M., Festen, Eleonora A.M., Alizadeh, Behrooz Z., van Leer-Buter, Coretta, Weersma, Rinse K., van Goor, Harry, Koets, A.P., Dijkstra, Gerard |
| Contributors: | Sub Immunologie, FAH theoretische epidemiologie, dFAH I&I |
| Source: | J Crohns Colitis |
| Publisher Information: | Oxford University Press (OUP), 2020. |
| Publication Year: | 2020 |
| Subject Terms: | Crohn's disease, Male, 2. Zero hunger, Antigens, Bacterial, Reproducibility of Results, nflammatory bowel disease, Original Articles, Middle Aged, Inflammatory Bowel Diseases, Antibodies, Bacterial, Immunoglobulin A, 3. Good health, Biological Therapy, Cohort Studies, Mycobacterium avium subsp. paratuberculosis, disease progression, Cross-Sectional Studies, Immunoglobulin M, Mycobacterium avium paratuberculosis, isotype-specific testing, Humans, genetics, Female, Genome-Wide Association Study |
| Description: | Background The role of Mycobacterium avium paratuberculosis [MAP] in inflammatory bowel disease [IBD], especially Crohn’s disease [CD] is controversial due conflicting results and lack of reproducibility and standardised tests. The current study focuses on the role of MAP in disease progression and genetic susceptibility, as MAP is likely one of many factors involved in the complex pathogenesis of IBD, potentially affecting a subgroup depending on genetic susceptibility. Methods Serum from 812 patients was evaluated with seven immunoglobulin [Ig] isotype-specific serology tests assessing humoral response to three different MAP antigens. For each of these in total 21 tests, the intra-assay and inter-assay coefficients were used to evaluate test accuracy. Reliable assays were subsequently analysed in relation to disease characteristics and need for biologic therapy/surgery. Genome-wide genotyping was available for all participants. Genetic determinants of humoral response to MAP antigens were evaluated using genome-wide association analysis and polygenic risk scores [PRS]. Results High IgA or IgM response to MAP2609 was associated with increased use of biologic therapy in CD and ulcerative colitis [UC] [odds ratios 2.69; 95% confidence interval 1.44–5.01; and 2.60, 1.46–4.64, respectively]. No associations were seen for risk of surgery [p-values > 0.29]. We could not identify genetic determinants nor polygenic risk scores for MAP response with genome-wide significance. Conclusions Extensive assays for serological response to MAP were evaluated using stringent criteria for reliability. Increased IgA and IgM response to MAP antigens was seen in patients exposed to biologic therapy, but no genetic determinants underlying this humoral response were found. |
| Document Type: | Article Other literature type |
| File Description: | application/pdf |
| Language: | English |
| ISSN: | 1876-4479 1873-9946 |
| DOI: | 10.1093/ecco-jcc/jjaa263 |
| Access URL: | https://academic.oup.com/ecco-jcc/article-pdf/15/8/1253/39556185/jjaa263.pdf https://pubmed.ncbi.nlm.nih.gov/33378524 https://research.rug.nl/en/publications/5aefc3a4-be67-4234-9447-7ff55c0bd796 https://hdl.handle.net/11370/5aefc3a4-be67-4234-9447-7ff55c0bd796 https://doi.org/10.1093/ecco-jcc/jjaa263 https://pubmed.ncbi.nlm.nih.gov/33378524/ https://research.wur.nl/en/publications/isotype-specific-antibody-responses-to-mycobacterium-avium-paratu https://www.narcis.nl/publication/RecordID/oai%3Apure.rug.nl%3Apublications%2F5aefc3a4-be67-4234-9447-7ff55c0bd796 https://europepmc.org/article/MED/33378524 https://academic.oup.com/ecco-jcc/article/15/8/1253/6055607 https://www.ncbi.nlm.nih.gov/pubmed/33378524 https://dspace.library.uu.nl/handle/1874/432470 |
| Rights: | CC BY NC URL: http://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (http://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
| Accession Number: | edsair.doi.dedup.....5dbe7617bf1e72e4b51d4795be29e55a |
| Database: | OpenAIRE |
Nájsť tento článok vo Web of Science | Abstract: | Background The role of Mycobacterium avium paratuberculosis [MAP] in inflammatory bowel disease [IBD], especially Crohn’s disease [CD] is controversial due conflicting results and lack of reproducibility and standardised tests. The current study focuses on the role of MAP in disease progression and genetic susceptibility, as MAP is likely one of many factors involved in the complex pathogenesis of IBD, potentially affecting a subgroup depending on genetic susceptibility. Methods Serum from 812 patients was evaluated with seven immunoglobulin [Ig] isotype-specific serology tests assessing humoral response to three different MAP antigens. For each of these in total 21 tests, the intra-assay and inter-assay coefficients were used to evaluate test accuracy. Reliable assays were subsequently analysed in relation to disease characteristics and need for biologic therapy/surgery. Genome-wide genotyping was available for all participants. Genetic determinants of humoral response to MAP antigens were evaluated using genome-wide association analysis and polygenic risk scores [PRS]. Results High IgA or IgM response to MAP2609 was associated with increased use of biologic therapy in CD and ulcerative colitis [UC] [odds ratios 2.69; 95% confidence interval 1.44–5.01; and 2.60, 1.46–4.64, respectively]. No associations were seen for risk of surgery [p-values > 0.29]. We could not identify genetic determinants nor polygenic risk scores for MAP response with genome-wide significance. Conclusions Extensive assays for serological response to MAP were evaluated using stringent criteria for reliability. Increased IgA and IgM response to MAP antigens was seen in patients exposed to biologic therapy, but no genetic determinants underlying this humoral response were found. |
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| ISSN: | 18764479 18739946 |
| DOI: | 10.1093/ecco-jcc/jjaa263 |