Exploring lgE antibodies for urologic chronic pelvic pain syndrome flare trigger identification and prevention - ABSTRACT Interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively referred to as urologic chronic pelvic pain syndrome (UCPPS), are common, costly, and debilitating syndromes characterized by persistent bladder and/or pelvic pain, and urinary symptoms. The etiology of UCPPS is unknown and its pathophysiology is poorly understood, making treatment challenging. Although many therapies have been proposed, none work consistently in all patients, and most are either invasive or prone to significant side effects. Clinical management is further challenged by the occurrence of frequent, painful, and often unpredictable symptom exacerbations or “flares.” Similar to the condition as a whole, little is known about the causes of flares or how to prevent and treat them. This question is further complicated by the large number of proposed flare triggers in the scientific and lay literature (>140 foods and >30 environmental factors), and the suspected individual nature of these triggers (i.e. each patient may have a different set of triggers). Therefore, new personalized flare trigger identification and prevention strategies are needed—for example, strategies guided by allergen-specific IgE (sIgE) antibody testing. This idea is supported by several lines of evidence, including promising findings from observational, experimental, and histopathologic studies; as well as in vitro mechanistic and animal model studies. Of particular relevance, two small experimental studies observed increased concentrations of urinary/bladder IgE antibody induced-mediators after allergen exposure guided by allergic sensitization testing in UCPPS patients, and three case reports observed symptom improvement after elimination of allergens to which patients mounted an IgE antibody response (N=10 patients combined). We also recently observed a borderline statistically significant higher prevalence of overall allergic sensitization in UCPPS cases than controls (90% vs. 40%, p=0.057) in a small pilot study. However, before we can translate these promising findings into flare prevention trials, we need data from at least one large, well-designed study to support a role for sIgE antibodies in UCPPS symptoms. With the proposed R21, we plan to generate these data. Specifically, we propose to leverage existing plasma from the NIH-sponsored Multidisciplinary Approach to the Study of Chronic Pelvic Pain epidemiologic case-control study (100 cases and 100 controls), along with state-of-the-art, multiplex sIgE antibody testing, to investigate whether UCPPS cases and those with a higher flare burden have greater evidence of overall and allergen-specific sensitization than healthy controls and those with a lower flare burden. We will also explore patient subgroups with the strongest associations. Together, these aims will provide much-needed evidence to support a future randomized controlled trial of flare prevention, informing not only the need for a trial, but also the nature of the intervention (e.g. personalized allergen elimination) and the patient subgroups most likely to benefit. Thus, this R21 holds the promise to inform new, safe, and effective complementary and/or integrative UCPPS management strategies.
