MAPP Research Network Study Clearly Finds Two Polyomaviruses In Urine of IC Patients
There is a small, vocal group of patients and clinicians who suggest that IC is the result of a chronic bacterial infection. This “all or none” theory ignores the thousands of patients who have developed urinary frequency, urgency, pressure and/or pain after chemotherapy, menopause, fibroid tumors, endometriosis, Tarlov cysts and, more frequently, pelvic floor muscle trauma and injury. That said, chronic infection could be present in a small group of patients. The question, of course, is what type of infection. Bacterial, fungal and viral infections should be considered.
The premiere IC research team in the USA, the Multidisciplinary Approach to Pelvic Pain (MAPP) Research Network, was the first discover that some patients appeared to have fungal infections in their urinary tract, particularly during flares(1). Using Next Generation DNA Urine testing, a second study found up to 13 species of fungus in some IC patients and that the more species a patient had, the greater their pain (2). Fungal growth (i.e. candida) can happen as a result of antibiotic use.
Researchers in Europe made a key discovery several years ago which also brought viral infection to the forefront. They found the Polyoma BK and Epstein Barr viruses in some patients with Hunner’s lesions(3,4,5). Another study used an antiviral medication as a therapy, noting the presence of polyomaviruses in IC patients.(6) Strangely, though, there was little discussion about the potential role of viral infections in the USA until the MAPP Research Network released their first pilot study of viruses found in the urine of some IC patients in Spring of 2020.(7)
This federally funded team focused on the family of human polyomaviruses because they are known to cause the development of vacuoles in the urothelium, often seen in IC patient biopsy results. Two polyomaviruses (JCPyV and BKPyV) have been known to establish life long persistent infections in the urinary tract that are also known to be periodically excreted, thus more easily identified, in urine. BKPyV is also a known cause for hemorrhagic cystitis in patients who are immune compromised and/or undergoing stem cell transplant, proving that the virus can cause disease in the urothelium.(8)
MAPP researchers studied 50 urine specimens collected from IC patients (five urine samples each from five men and five women) from across the country. Urine was collected at baseline, six months and 12 months of clinic visits, with atleast one of the samples collected during an IC flare. A flares and non-flare samples were also collected at home.
Next Generation DNA studies
After their preliminary analysis of each sample, researchers created five different combined “pools” by combining 200UL from 10 randomly selected urine samples. Using Next Generation DNA Sequencing, they extracted both DNA and RNA segments of each pool. Polyoma JC DNA was detected in 4/5 pools. DNA was evenly distributed between early and late regions of the genome. These pools also contained “late regions” of Polyoma JC RNA suggesting that infected cells were present in the sample. In contrast, Polyoma BK DNA was identified in only 1 of the 5 pools and no RNA found.
The research team then utilized another form of testing, PCR analysis, to confirm these results. This revealed that 70% of participants were found to have Polyoma BK DNA in their urine, though not in all samples from the same individual. The Polyoma JC virus was detected in 30% of participants but the prevalence in patients was higher. One patient had JC in all of her specimens. Another had JC in 4 out of 5 five specimens, and still another had JC in 3 out of 5 specimens. Only one patient had consistent shedding of the BK virus in 4 out of 5 samples. In all, 12/50 urine specimens had JC and 11/50 had BK.
The presence of virus did correlate with increased symptoms & flares
Patients with a positive polyoma JC finding had significantly more pain severity when compared to those who did not have the virus (19.9 vs. 14.2). Similarly, urinary severity was higher in those with JC. (17.0 vs. 13.2) Patients with a positive BK finding also had more intense pain (16.6 vs. 15.3). In this group of 7 patients, 6/7 had higher pain and urinary scores when the BK was detectable in their urine.
JC was detected in 25% of flare samples and 23% of non-flare samples. BK was detected in 30% of flare samples and 17% of non flare samples.
This study establishes that both polyomaviruses may be present in infected urinary cells in some IC patients. Clearly, additional studies with a larger population of patients is needed to determine what role, if any, that viruses may play in IC. This certainly should give pause to those who suggest that IC is the result of chronic bacterial infection. In fact, viruses could play a much larger role than previously realized. We can’t wait to see more research studies on this topic.
- Nickel JC, et al. Assessment of the Lower Urinary Tract Microbiota during Symptom Flare in Women with Urologic Chronic Pelvic Pain Syndrome: A MAPP Network Study. J Urol. 2016 Feb;195(2):356-62
- Nickel JC, et. al. Urinary fungi associated with urinary symptom severity among women with interstitial cystitis/bladder pain syndrome (IC/BPS). World J. Urol. Feb. 2020, Epub April 26, 2019 Volume 38, No. 2.
- Jhang JF, et. al. Epstein-Barr Virus as a Potential Etiology of Persistent Bladder Inflammation in Human Interstitial Cystitis/Bladder Pain Syndrome. J Urol Sept. 2019, Vol. 200, No. 3
- Winter B, et al. A Case Control Study Reveals that Polyomaviruria Is Significantly Associated with Interstitial Cystitis and Vesical Ulceration. PLoS One. 2015; 10(9): e0137310.
- Van der Aa F, et al. Polyomavirus BK–a potential new therapeutic target for painful bladder syndrome/interstitial cystitis? Med Hypotheses. 2014 Sep;83(3):317-20.
- Eisen DP, et al. Decreased viral load and symptoms of polyomavirus associated chronic interstitial cystitis after intravesical cidofovir treatment. Clin Infect Dis 48(9):e86-e88.
- Robles M, et al. Analysis of viruses present in urine from patients with interstitial cystitis. Virus Genes. Published online May 15, 2020
- Bennett S, et al. BK polyomavirus: emerging pathogen. Microbes Infect. 2012 Aug: 14(9):672-683