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LAS VEGAS — Is interstitial cystitis (IC) an autoimmune disorder? New evidence suggests at least for some patients, the answer is yes.

Researchers have discovered a potential antigen involved in the development of IC with Hunner lesions, they reported here at the American Urological Association (AUA) 2025 Annual Meeting.

Genomic typing suggests certain human leucocyte antigens (HLAs) are associated with this form of the condition, which is marked by inflamed lesions lining the bladder wall, researchers said.

“The HLAs are the gold standard of evidence that a disease is autoimmune,” said Joel N.H. Stern, PhD, professor of urology, neurology, and molecular school of medicine at the Zucker School of Medicine at Hofstra/Northwell in Uniondale, New York, who helped conduct the research.

Inna Tabansky Stern, MD, PhD, urology resident at the Renaissance School of Medicine, Stony Brook University, Long Island, New York, and Stern’s wife, presented the findings.

IC/bladder pain syndrome (IC/BPS) affects eight million women and three million men in the United States, some of whom may also have autoimmune conditions like Sjögren syndrome or Hashimoto disease. A hallmark of the condition is at least 6 weeks of painful urination without any infection.

Most people with IC/BPS have no abnormal lesions on their bladder wall. Treatments for Hunner lesions include surgical excisions or triamcinolone injections.

The researchers recruited 12 patients with IC/BPS and Hunner lesions and seven without the lesions. They conducted high resolution genomic typing on blood samples from the group and found a higher frequency of two HLA alleles in people with Hunner lesions.

“We figured if we understand the HLAs we can start looking at and maybe identifying an antigen that’s driving the whole inflammatory response,” Joel Stern said. One possible antigen is uroplakin, a protein on the bladder wall that appeared to have the ability to bind to HLA molecules. In a modeling analysis, they determined the protein, and the molecules did indeed bind.

Should uroplakin prove a driver of Hunner lesions in IC, it might be a target for potential treatments. His lab is exploring the connection further.

“There could be treatments targeting the HLA and the immune response, outcompeting the antigen,” he said. “There are many possibilities, this does open up a new field within interstitial cystitis.”

“Any genetic evidence linking genotype to phenotype is amazing” to better understand the drivers of IC/BPS, said Catherine Brownstein, MPH, PhD, geneticist at Boston Children’s Hospital and assistant professor at Harvard Medical School, Boston.

“That’s the way we going to get to biomarkers and genetic guided diagnosis and targeted therapies.”

Brownstein and her colleagues reported rare variants in the ATP2C1 and ATP2A2 genes affect the development of IC/BPS. That analysis included 348 people with IC/BPS and 11,981 people without the illness.

“There’s no reason to assume everyone has one cause. I don’t think it’s a simple gene-phenotype association,” Brownstein said.

IC/BPS is likely underdiagnosed, given the condition is a diagnosis of exclusion with nonspecific symptoms. Understanding all its causes is urgent, she added; as many as 40% of people with IC/BPS are at risk for suicide.

“It’s so incredibly painful, and we still don’t know the triggers,” she said. “The more we’re able to throw at this and treat it from multiple angles, the better off patients will be.”

Joel Stern, MD, reported receiving funding from the National Institute of Diabetes and Digestive and Kidney Diseases. Brownstein reported having no relevant financial conflicts of interest.

Marcus A. Banks, MA, is a journalist based near New York City who covers health news with a focus on new cancer research. His work appears in Medscape Medical News, Cancer Today, The Scientist, Gastroenterology & Endoscopy News, Slate, TCTMD, and Spectrum.