Presentation Authors: Jennifer Anger*, Weston Spivia, A. Lenore Ackerman, Karyn Eilber, Jayoung Kim, Qin Fu, Michael Freeman, Jennifer Van Eyk, Los Angeles, CA
Introduction: The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) network is, to date, the largest cohort study of men and women with urologic chronic pelvic pain syndrome (UCPPS) followed over time. The MAPP network has identified clinically meaningful subtypes, or "phenotypes" of UCPPS. Herein we sought to correlate the serum proteome with specific phenotypes of UCPPS.
Methods: We collected serum samples from 400 patients who participated in the MAPP network. Multiple reaction monitoring (MRM) is a mass spectrometry (MS) method that can target selective peptides for the detection and quantitation of a protein. We applied MRM-MS methods with a full suite of peptide standards for 72 pre-selected targeted proteins that are involved in many disease and inflammatory processes. Categories of study were control vs UCPPS vs positive control (those without pelvic pain but with other pain syndromes outside the pelvis). We then matched patients according to UCPPS characteristics such as pain severity, sex, pelvic pain vs. pelvic pain and beyond (widespread pain), and painful urgency/painful bladder filling. These were processed by MS and data were analyzed using MultiQuant 2.1 (ABSciex, Framingham, MA).
Results: We found that proteins had significant differential expression across categories, including age, sex, cohort (control vs. UCPPS), and urinary severity. Alpha-1-antichymotrypsin (AACT) decreased significantly with painful filling and urgency (Figure 1). Although its role in UCPPS is unclear, it inhibits neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to angiotensin-2. Alpha-1-antitrypsin (A1AT), an inhibitor of serine proteases, and complement C5, a member of the complement cascade, followed the same pattern as A1AT. Vitamin D-binding protein (VTDB), which is involved in inflammation, also decreased with painful urgency. Alpha-2-macroglobulin (A2M) was similarly decreased in patients with pelvic pain and beyond (vs. pelvic pain only).
Conclusions: We find a distinct serum proteomic signature that occurs with painful urinary urgency. Our results suggest the potential for identifying subtypes of UCPPS in part using serum biomarkers. These findings link clinical phenotypes with underlying biology in UCPPS.