Diagnosis of Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder affecting the gastrointestinal tract and is characterized by a progressive and unpredictable disease course. There has been a global rise in the incidence of IBD over the last few decades. Considering the chronic, progressive nature of IBD and the costliness of its treatment, the rise of IBD entails a growing socioeconomic burden. A growing body of evidence suggests that IBD may be the result of an interaction between genetic factors, environmental factors, life style factors as diet, antibiotics, intestinal barrier dysfunctions and altered microbes.

According to a large meta-analysis of population-based studies (2000-2022) The global prevalence rates of IBD was 229.7 per 100,000 persons and the incidence was 9.7 per 100,000 persons. Europe had the highest prevalence rates of IBD while the highest IBD incidence was seen in Oceania. Research in the Arab world suggests that the IBD prevalence in Arab countries increased from \~28.9 to \~34 cases per 100,000 between 2009 and 2019, with Egypt as one of the leading countries producing IBD research output. According to a recent global burden study (1990-2021), the absolute number of deaths attributed to IBD nearly doubled: from \~21,418 in 1990 to \~42,422 in 2021 - reflecting growing numbers of people living with IBD.

It is characterized by remission and exacerbation course. Bloody stools, abdominal pain, weight loss, chronic diarrhea, and the presence of immune-mediated extra-intestinal manifestations represent the disease's symptoms.

Over time, severe inflammation within the intestine can lead to serious complications, including ulcers, narrowing of the intestinal lumen, and even perforations. Notably, IBD can cause considerable damage to the digestive system, resulting in substantial tissue injury, reduced intestinal functionality, associated disability, and a state of systemic inflammation that may impact the individual's overall health. Also, Patients with inflammatory bowel disease have an increased risk of developing colorectal cancer.

Inflammatory bowel disease manifests primarily in two major forms: Crohn's disease (CD) and ulcerative colitis (UC) . Crohn's disease typically exhibits lesions in the ileum and colon, characterized by intermittent inflammatory changes of the permeable wall while Ulcerative colitis predominately develops on the mucosal surface of the rectum, displaying continuous inflammatory foci.

The causative genes responsible for IBD remain incompletely characterized, highlighting the necessity for a thorough investigation of crucial molecular signatures involved in its development, which may provide potential avenues for effective therapies. In recent years, there has been a significant expansion in the era of RNA biology, showing the sophisticated mechanisms of gene regulation that extend far beyond the conventional protein-coding genes. While messenger RNAs (mRNAs) are transcribed and translated into proteins, most of the genome is transcribed into RNA molecules known as non-coding RNAs (ncRNAs) that do not ultimately translate into proteins.

Over 70% of genetic associations in IBD occur in the noncoding regions of the genome. The major classes of ncRNAs that have gained increased research attention are long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs). Long noncoding RNA are noncoding RNAs (not get translated into protein) with a length of more than 200 base pairs , and contribute to the etiology of various diseases such as respiratory diseases, inflammatory diseases and tumors. lncRNAs are major players in the inflammatory pathway as they have crucial roles in not only expression but also differentiation of cytokines and immune cells, respectively.

Nuclear enriched abundant transcript 1 (NEAT1) is long noncoding RNA that is a key component in building the ribo-riboprotein complex to regulate DNA-mediated activation of innate immune responses and has also been found to play an important role in innate immune responses. It targets numerous genomic regions in various cells, mainly involving active genes, revealing that it is a regulator for plenty of active genes and signal pathways. It is involved in the development of colitis by acting on miR-204-5p axis through activating PI3K-AKT signaling pathway and the NF-κB signaling pathway leading to increase of Interleukin-6 (IL-6) , Imterleukin-1B (IL-1B) and Tumor necrosis factor-a (TNF-a) that result in inflammation and cell apoptosis .

Anti-sense Non RNA in the INLK4 locus (ANRIL) is long non coding RNA that doesn't encode a protein; instead, it regulates gene expression at transcriptional, epigenetic, and post-transcriptional levels . It has a pro-inflammatory role in many inflammatory and immune diseases as Coronary artery disease, Chronic kidney disease and Inflammatory bowel disease. In IBD, it mediates nuclear factor κB (NF-κB) to influence inflammation through its effects on intestinal epithelial cells, besides providing future clues for clinical diagnosis. It activates NF-ΚB leading to increase of IL-6 , IL-1B and TNF-a that result in cell apoptosis . Also, Up-regulation of ANRIL could decrease the expression of miR-199a and increase the number of apoptotic cells.

Nuclear factor kappa B (NF-KB) expression is accompanied by increased production of pro-inflammatory cytokines, such as TNF-α, IL-1 and IL-6, due to the actions of NF-kB in expanding the capacity of these cells to produce inflammatory mediators. Predominantly, the NF-kB derived pro-inflammatory cytokines are responsible for two mechanisms involved in the development of IBD lesions. Firstly, the produced pro-inflammatory cytokines directly mediate mucosal tissue damage by principally up-regulation of matrix metalloproteinases production and secretion in the intestinal lumen. Secondly, NF-kB derived pro-inflammatory cytokines also mediate the stimulation, activation, and differentiation of immunological cells derived from lamina propria of the bowel mucosa, resulting in chronic inflammation and, therefore, in the perpetuation of mucosal damage.

So the investigators will measure NEAT1 and ANRIL as diagnostic biomarkers for IBD together with the Inflammatory mediator NF-KB. This can be done by non invasive blood sample instead of the invasive endoscopic biopsy.

• To evaluate the correlation between the studied biomarkers among the studied groups explored and both their clinical presentations and the inflammatory mediators like NF-KB signaling pathway. [Срок оценки: Baseline]