Food-specific antibodies and urologic chronic pelvic pain syndrome.

(请保存在Word中，不要保存为PDF) 在此输入文本，它是您的应用程序的新摘要信息。此部分不得超过30行文本。 间质性膀胱炎/膀胱痛综合征(IC/BPS)和慢性前列腺炎/慢性盆腔疼痛综合征(CP/CPPS)是一种常见的、代价高昂的衰弱综合征，其特征是持续性的膀胱和/或盆腔疼痛，以及尿路症状，如紧迫感和频率。这些疾病的病因被称为泌尿系慢性盆腔疼痛综合征(UCPPS)，其原因尚不清楚，其病理生理机制也鲜为人知，这使得治疗具有挑战性。虽然已经提出了几种治疗UCPPS的方法，但都没有找到 在所有患者中工作一致，并且每个患者要么是侵入性的，要么容易产生显著的副作用。因此，显然需要新的治疗方法。其中一种很有希望但尚未得到充分研究的方法是饮食排斥。这一方法得到了一项小型单臂试验(n=10)、两份病例报告、我们最近采用多学科方法研究慢性盆腔疼痛1(MAPP-1)研究网络病例交叉研究以及几项患者调查的支持，这些研究表明，很大比例的患者认为饮食引发了他们的红肿。然而，由于患者报告的触发因素众多且范围广泛(多达144个候选)，确定一种适用于所有患者的共同饮食已被证明具有挑战性。消除饮食也很难实施和测试，因为在“消除”阶段需要消除大量可能的食物触发因素，在“重新引入”阶段需要重新引入大量食物，以及盲目消除饮食的挑战。因此，迫切需要使这些饮食个性化的工具。在对偏头痛、克罗恩病、肠易激综合征和哮喘患者的试点试验中，研究人员 观察到在排除饮食后症状显著减少，这些饮食是通过食物特异性抗体浓度来告知的。这种方法是有希望的，因为它减少了饮食排除的时间、复杂性和负担，同时增加了其成功的机会和严格的盲法评估的潜力。食物特异性免疫球蛋白抗体也是告知UCPPS治疗的合理候选者，因为它们通过UCPPS病理中涉及的生物机制(例如肥大细胞脱颗粒和组胺释放)起作用，并且在与患者报告的食物触发经验一致的“延迟”时间段(几小时到几天)内起作用。然而，在我们可以启动针对UCPPS的食物特异性免疫球蛋白抗体告知排除饮食的随机对照试验(RCT)之前，需要更多的经验证据来支持这一方法。对于生物标记物信息排除饮食已显示出初步疗效的许多情况，研究人员首先证明了患者比对照组更有可能出现食物特异性免疫球蛋白抗体。我们还在10名UCPPS患者的小样本中产生了有希望的试点数据(100%有食物特异性抗体 相比之下，历史控制的比例为15%-33%)。在这项R01中，我们计划在这些有希望的发现的基础上，使用现有的血浆样本和来自MAPP-1研究的100名患者和100名对照的临床表型数据，正式测试UCPPS患者是否比对照组对食物更敏感。

(PLEASE KEEP IN WORD, DO NOT PDF) Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. Interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS), are common, costly, and debilitating syndromes characterized by persistent bladder and/or pelvic pain, and urinary symptoms, such as urgency and frequency. The cause of these conditions, together referred to as urologic chronic pelvic pain syndrome (UCPPS), is unknown and their pathophysiology is poorly understood,making treatment challenging. Although several therapies have been proposed for UCPPS, none has been found to work consistently in all patients and each is either invasive or prone to significant side effects. Therefore, new therapeutic approaches are clearly needed. One such promising, but understudied, approach is dietary exclusion. This approach is supported by findings from one small single-arm trial (n=10), two case reports, our recent Multidisciplinary Approach to the Study of Chronic Pelvic Pain 1 (MAPP-1) Research Network case-crossover study, and several patient surveys indicating that a large proportion of patients believe that diet triggers their flares. However, as patient-reported triggers are numerous and wide-ranging (up to 144 candidates), identification of one common diet suitable for all patients has proven challenging. Elimination diets are also difficult to implement and test because of the large number of possible food triggers that need to be eliminated in the “elimination” phase, the large number that need to be re-introduced in the “re-introduction” phase, and the challenges of blinding elimination diets. Therefore, tools to personalize these diets are urgently needed. In pilot trials of patients with migraines, Crohn’s disease, irritable bowel syndrome, and asthma, researchers have observed significant symptom reductions following exclusion diets informed by food-specific IgG antibody concentrations. This approach is promising because it reduces the time, complexity, and burden of dietary exclusion, while simultaneously increasing its chance of success and potential for rigorous blinded evaluation. Food-specific IgG antibodies are also plausible candidates to inform UCPPS therapy because they act by biologic mechanisms implicated in UCPPS pathology (e.g. mast cell degranulation and histamine release) and in a “delayed” time frame (hours to days) consistent with patient-reported food trigger experiences. However, before we can initiate a randomized controlled trial (RCT) of food-specific IgG antibody-informed exclusion diets for UCPPS, additional empirical evidence is necessary to support this approach. For many conditions for which biomarker-informed exclusion diets have shown preliminary efficacy, researchers first demonstrated a greater likelihood of having food-specific IgG antibodies in patients than controls. We have also generated promising pilot data in a small sample of 10 UCPPS patients (100% had food-specific IgG antibodies compared to 15-33% of historical controls). In this R01, we plan to build on these promising findings by formally testing whether UCPPS patients have greater food sensitivity than controls, using existing plasma samples and clinical phenotyping data from 100 cases and 100 controls from the MAPP-1 study.