Gene Expression Profiling of CD8+ T-Cells to Determine Prognosis in IBD Patients

Inflammatory Bowel Disease will affect each person differently. Some patients will have an indolent or less aggressive form of the disease while others have a more severe form of the disease, leading to many serious complications, and, in extreme cases, death. However, current conventional treatments are the same for every patient: treatment with potent immunosuppressents and/or surgery. While suppressing the immune system and/or surgical procedures in patients with severe forms of IBD might be beneficial for them, patients with an indolent form of the disease might not benefit from such aggressive therapies. Instead, these therapies may cause life-threatening problems in patients with a less aggressive form of the disease, including developing opportunistic infections, cancer, and demyelination. However, researchers are trying to determine if it may be possible to determine an individual IBD patient's prognosis in order to personalize treatments for him/her so that it is more appropriate.

The main idea behind this study is based on the observation that a CD8+ T Cell transcriptional signature could be found in two unrelated autoimmune diseases: Systemic Lupus Erythematosus (SLE) and Vasculitis. It has been noted that although both of these diseases are completely different from each other, they both go through a relapse-remitting cycle. This cycle is also seen in Inflammatory Bowel disease. Thus, the goal of the authors of this article was to find a transcriptional signature that is common to both Crohn's Disease and Ulcerative Colitis.

The study consisted of 35 patients with CD and 32 patients with UC. Blood was drawn from the patients and CD4 and CD8 T Cells were selected from peripheral blood mononuclear cells for whole-genome transcriptional analysis. They all were given conventional therapies to treat the disease. Approximately 3,403 genes were determined to be expressed differentially in the CD group, while 4,186 genes were expressed in the UC group. Further analysis of the data by the researchers revealed that there was significant overlap between transcriptional signatures for both CD and UC. These genes were believed to be responsible for activating CD8+ T Cells. Also, this is analogous to the significant overlap found in transcriptional signatures between SLE and Vasculitis. Researchers further analyzed the data and determined that the patients could be further classified into smaller subgroups: IBD1 and IBD2. There was increased upregulation in the expression of CD8+ T Cell activating genes in IBD1 patients, which experienced a more severe form of the disease compared to the IBD2 patients who were considered to have a more indolent form of the disease. As such, the researchers were able to determine that patients with a higher expression of CD8+ T Cell activating genes in the IBD1 group would require more aggressive and continuous therapies than the patients in the IBD2 group, thus personalizing treatments for each individual patient.

Article Link:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196314/?tool=pubmed