Apart from the unexplained occurrence of pus cells (leukocytes) most of us are familiar with, another common finding accompanying an IC/PBS sufferer’s negative UTI test is a show of elevated epithelial cells. The lab report generally interprets this as contamination. What’s interesting about this is, if someone has a confirmed urinary infection, elevated epithelial cells are considered another positive sign of the infection. If someone doesn’t have a confirmed urinary infection, elevated epithelial cells are put down to contamination. What if the reason behind epithelial cells accompanying a negative test wasn’t so different to those found with a proven positive urinary infection? Could epithelial cells be more of a clue than a contaminant?
Epithelial cell exfoliation is a known human immune response to bacterial invasion. It’s a proven response with infections of the bladder as well as the gastric tract. Scott Hultgren’s team highlights epithelial cell exfoliation in relation to intracellular bacterial communities and uropathogenic Escherichia coli (UPEC), referring to it as a defence mechanism, “numerous host defences against this process, including inflammasome activation and programed urothelial exfoliation and bacterial expulsion via a TRPML3-mediated mechanism, have been uncovered” (2016). Along the same line, James Malone-Lee describes increased epithelial cell sloughing as an “innate immune response” that suggests inflammation by low-grade infection in the urinary tract (2013). Excess epithelial cell shedding is also reported by researchers as a common immune response in intestinal infections where it “helps expel colonized pathogens, confine bacterial spreading, and localize inflammation” (cited in Kim, 2010).
What if the epithelial cells found in negative urine samples weren’t routinely caused by contamination, and the importance of these cells was being overlooked?
This is what’s known about epithelial cells in urine:
> The bladder lining sheds naturally and it’s normal to have one or two epithelial cells in a urine sample.
> Higher than normal amounts of epithelial cells in urine samples can be caused by infection, kidney disease (nephrotic syndrome) or contamination from vaginal epithelial cells.
> Research shows bladder wall cells shed as a first line defence mechanism by the host’s immune system to rid the epithelium of invading pathogens.
> Mice models have demonstrated it takes around 10 months to naturally shed half the cells in the bladder lining. When under attack by harmful acute bacteria, rapid cell exfoliation takes place (Beachy, 2010).
> When a UTI is confirmed, epithelial cells are often reported as positive by few (+), moderate (++) and many (+++) per high power field (HPF).
> When excess epithelial cells are found in a sample that has no significant growth or mixed growth, it’s written-off as contamination from the distal urethra in men and the opening of the vagina in women.
> In 1985, research was conducted on 33 patients with recurrent UTI symptoms who had not responded to antibiotic therapy. They found the urothelium was grossly disrupted with the loss of epithelial cells, when compared to normal, uninfected bladders. The degree of uro-epithelial disturbance was greatest in patients with histories of urinary tract infections lasting more than 4 months. These findings suggest bacteriological examination of the urine doesn’t always reflect bacterial infection on the bladder surface, nor disruption of the uro-epithelium (Elliott, Reed, Slack and Bishop).
> The more cells that are shed reflects the severity of infection and possibly the stronger the immune response to the invasion (Horsley, Malone-Lee and Holland, 2013).
> In 2001, US researchers demonstrated bladder epithelial turnover in association with the re-emergence of uropathogenic Escherichia coli (UPEC) from the reservoir inside the bladder (Mulvey, Schilling and Hultgren).
> In 2013, UK research used immunofluorescence to distinguish cellular origin of epithelial cells in properly collected urine samples. Contrary to popular belief, the study concluded the vast majority of epithelial cells found in urine originate in the urinary tract, verifying the presence of epithelial cells doesn’t mean the MSU is contaminated by vaginal contents (Horsley, Tuz, Swamy, Malone-Lee and Rohn).
> In 2013, UK research found increased urothelial cell shedding in association with lower urinary tract symptoms (LUTS) in women. Like with studies of acute UTI in humans and mice, cell sloughing is known to be a common response to infection. This intense shedding leaves a gap in the epithelial layer leaving it vulnerable to further invasion. The research concluded shedding is an innate immune response which suggests inflammation by low-grade infection in LUTS (Horsley et al.).
> The same epithelial cell exfoliation is commonly noted in gastric infections. In 2010, Japanese researchers commented that epithelial cells in the gut will rapidly shed in an immune response to expel colonising pathogens and stop the spread of an invading infection (Kim, Ashida, Ogawa, Yoshikawa, Mimuro and Sasakawa). This was also noted by Radtke and Clevers in 2005 and again by Chichlowski and Hale in 2008.
Given these fairly recent facts, could overlooking epithelial cells as contaminants be a longstanding mistake? What if these epithelial cells were a clue to something more important?
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