Professor Jo Spencer, King's College London, and her team are trying to understand an interesting observation; that people who have their appendix removed in early life are less likely to get Ulcerative Colitis.
The appendix contains many immune cells called B cells. The team were keen to know if the B cells in people with Colitis had altered properties compared to B cells from healthy people.
They found that the B cells in the blood of patients with Crohn’s or Colitis are depleted of an immune cell population called double negative B cells. This population has previously been linked with rheumatoid inflammatory diseases and ageing but by an increased frequency in the blood rather than a decrease as seen in Crohn's or Colitis.
The team also found that the double negative B cells that are depleted from the blood in Crohn's or Colitis are elevated in the gut-associated lymphoid tissue (GALT) from around the appendix.
This discovery that the immune system of someone with Crohn's or Colitis might be different is intriguing, and it’s important to try to determine what that means for people. The team therefore tested the possibility that the double negative B cells may contribute to the production of cytokines, a cell signalling protein that leads to inflammation.
Tumor necrosis factor (TNF) is a type of cytokine and drugs known as anti-TNFs and can be used to treat Crohn’s or Colitis by blocking it (infliximab and adalimumab). However, the team found no evidence that B cells produce any more TNF proteins in people with Crohn’s or Colitis than healthy people.
Unexpectedly, the depletion of double negative B cells in the blood in Colitis was also seen in Crohn’s Disease. It was even seen in mild Crohn's and Colitis and remained in patients responding to therapy, suggesting that this is a fundamental feature of the immune system in Crohn's and Colitis.
The researchers will continue to build on this observation and seek ways in which GALT and cell interactions in Ulcerative Colitis and healthy people are different, in a search for ways to intervene and target inflammation.
This research was published in the journal Frontiers in Immunology and funded by Crohn's & Colitis UK.