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