Validation of immune-based biomarkers for endometriosis.

ABSTRACT Endometriosis is a highly prevalent gynecologic disease characterized by severe pelvic pain and infertility that negatively impacts the wellbeing and quality of life of millions of women worldwide Despite decades of basic and clinical research on endometriosis there is limited understanding of its pathophysiology and no specific non invasive diagnostic assays are available As a result diagnosis can only be made via a surgical procedure e g laparoscopy significant delays in diagnosis have been reported in average of years since onset of symptoms and there is still no definitive cure We have recently applied an innovative high throughput human protein chip based platform to the discovery of the serum autoimmune component of endometriosis patients and controls Using CDIandapos s HuProt protein microarray v containing over yeast derived recombinant human proteins we decoded the antigen specificity of auto antibodies AAbs present at different levels in sera of women with endometriosis compared to controls We have identified AAbs that are present at higher or lower levels in sera from women with endometriosis compared to controls and that could be used as the basis of a non invasive immune based diagnostic assay We now propose to validate our findings by testing a larger cohort of samples using a focused protein array based on the differentially expressed AAbs and to determine the usefulness of the final panel as a non invasive diagnostic test for endometriosis The long term goal of this STTR Phase I study is to fill an important void in the clinical management of women with pelvic pain and or infertility by developing a non invasive diagnostic assay for endometriosis We propose to address this goal via one specific aim to assess the diagnostic potential of AAbs identified during the discovery phase on a larger sample set of patients and controls already available from the Ponce School of Medicine PSM Endometriosis Research Program ERP andapos s biobank consisting of biospecimens and data from Puerto Rican subjects For that purpose we will construct a focused array mini chip of human autoantigens selected based on the most differentially detected AAbs in the sera of women with endometriosis compared to controls and will conduct a retrospective validation study by analyzing serum samples from a larger cohort of patients and controls These data will serve to refine the number of biomarkers that maintain their high discriminatory power and will support the use of these focused mini chips as a diagnostic tool to be used in clinical settings In Phase we will propose to expand the validation of these potential biomarkers by utilizing the focused array approach to include sera from patients from other research cohorts to increase the ethnic coverage of the test utilizing at least one or more of the biomarkers identified in Phase I and to explore other more cost effective and practical assay formats Development of specific non invasive tests to allow identification of women with pelvic pain and or infertility at risk of having endometriosis using an easily obtainable serum sample is of high priority in the Womenandapos s Health Gynecology fields given the high prevalence of pelvic pain and endometriosis among women of reproductive age and the risk of complications disease progression beyond the pelvis hysterectomy infertility ovarian cancer in those not promptly diagnosed and treated KEYWORDS Endometriosis Diagnostics Non invasive diagnosis Autoimmunity Autoantibodies Autoantigens Protein Microarrays Multiplex High Throughout Proteomics Pelvic Pain Womenandapos s HealthProject Narrative A non invasive serum based diagnostic for Endometriosis or the lack there of has been a major issue for the proper and early diagnosis for this painful disease If the diagnosis and treatment of for this disease is to mature then a series of well validated reproducible serum biomarkers are much needed We have discovered a group of autoantibodies differentially expressed in the serum of patients with endometriosis and more importantly we have developed an approach to rapidly validate the usefulness of these biomarkers as potential diagnostic tools The validation of at least one of these biomarkers will directly benefit thousands of endometriosis patients globally