Published online May 28, 2019. doi: 10.3748/wjg.v25.i20.2473
Peer-review started: February 15, 2019
First decision: April 4, 2019
Revised: April 20, 2019
Accepted: April 29, 2019
Article in press: April 29, 2019
Published online: May 28, 2019
Intestinal tuberculosis (ITB) and Crohn’s disease (CD) are two kinds of intestinal granulomatous diseases with very similar clinical manifestations. In recent years, with the changes in epidemiology, these two diseases have often been difficult to identify during clinical work in developing countries. Misdiagnosis can have serious consequences for the patients. The impact of individual genetic diversity on ITB and CD susceptibility and the specific mechanism are still not clear.
Recent studies have shown that Th17 cells play a key role in mucosal immune responses. Differentiation of Th17 cells is regulated by the interleukin (IL)-23/IL-17 axis. We hypothesized that this axis-related gene functional polymorphism sites can affect the susceptibility to ITB and CD.
To determine the difference in genetic susceptibility between ITB and CD and to further elucidate the specific mechanism of action of differentially distributed genes in the occurrence and development of diseases, which will contribute to the identification of diseases and the implementation of individualized treatment.
This case-control study was conducted by investigating ITB and CD patients who were admitted to the Jiangxi Provincial People's Hospital in the past 10 years. A total of 133 ITB, 128 CD, and 500 healthy patients were included, and their clinical data were recorded. Based on our previous findings, four single-nucleotide polymorphisms (SNP) loci located in genes involved in the IL-23/IL-17 axis were screened for genotyping of the subjects. Based on the results of the typing, we focused on the study of IL22 rs2227473. The dual luciferase reporter assay system was used to determine the transcriptional regulatory effect of rs2227473 on IL-22, and the IL-22-IL-22R axis was analysed by immunohistochemistry in different intestinal diseases.
According to our study, T cell spot test positive rate and abnormal lung imaging are helpful for identifying ITB and CD. Using unconditional logistic regression analysis to adjust covariates suggests that rs2227473 and rs1143627 polymorphisms affect ITB susceptibility instead of CD. Dual luciferase assay showed that the rs2227473 locus affects the transcriptional activity of the IL22 gene. Immunohistochemical staining suggests that the expression of IL-22R1 is significantly increased in ITB and CD compared with intestinal polyps and colon cancer. This differential expression may be used to identify intestinal diseases; more importantly, IL-22R1 is expressed in intestinal lymphoid tissues, especially in multinucleated giant cells. This finding breaks the notion that IL-22R1 expression is generally restricted to non-haematopoietic cells.
IL22 SNP rs2227473 G allele is a risk factor for developing ITB. This finding is informative for further studies of the pathogenesis of tuberculosis. Furthermore, by analysing the baseline characteristics of the surveyed population, we discovered that the findings from T cell spot test and lung imaging were valuable for the differential diagnosis between ITB and CD, providing evidence-based support for clinical diagnosis. Finally, we found that IL-22R1 is expressed in multinucleated giant cells and that the IL-22-IL-22R axis may play an important role in the coordination of innate and adaptive immunity.
The IL-23/IL-17 axis gene polymorphisms may affect the occurrence and development of tuberculosis by affecting the differentiation of Th17 cells and the expression of related cytokines. IL-22R1 plays an important role not only in maintaining mucosal barrier function in innate immunity but also in the adaptive immunity of inflammatory diseases, indicating that previous views on the safety of IL-22-IL-22R1 systemic therapy need to be reassessed.