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A novel T7 phage display technology to detect sarcoidosis specific antigens

Award Number: R01HL150474
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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A novel T7 phage display technology to detect sarcoidosis specific antigens - Sarcoidosis is an inflammatory disease of unknown etiology that occurs worldwide and is characterized by granuloma formation in different organs. No specific test has been developed to diagnose this disease. Confirmation of non-caseating granuloma in tissue biopsy of involved organs in the absence of other causes is the current state of the art for diagnosing sarcoidosis. We propose to test the hypothesis that overall immunity plays a prominent role in the pathogenesis of sarcoidosis, since abnormalities of the immune function and the presence of various antibodies/autoantibodies occurs in this disorder. Sarcoidosis and tuberculosis have clinical and pathological similarities. Despite isolation of various components of Mycobacterium tuberculosis (MTB) from sarcoidosis tissues, sarcoidosis subjects react to tuberculin skin test (PPD) negatively. In contrast to sarcoidosis latently infected individuals with TB (LTBI) respond to PPD with delayed type hypersensitivity reaction. Using a high throughput method, we developed a complex cDNA library derived from tissues of sarcoidosis patients. We constructed a microarray platform from this cDNA library containing large numbers of sarcoidosis clones and immunoscreened this platform with sera from patients with sarcoidosis, controls and other respiratory diseases. We identified a panel of biomarkers/classifiers with high sensitivity and specificity that can discriminate between sera of patients with sarcoidosis, healthy controls other respiratory diseases. Thus, our technology allows us to test the hypothesis that sarcoidosis is an immune disorder triggered by a group of specific antigens, which differ from LTBI antigens. Furthermore, these specific antigen peptides are capable of inducing granuloma in vitro in sarcoidosis peripheral mononuclear cells (PBMCs). To test this hypothesis, we will selectively biopan our T7 phage cDNA display library with sera of diverse sarcoidosis and LTBI subjects to select diversified clones to increase the antigen repertoire to construct a comprehensive antigen microarray platform. Second, we propose to use a large sample size from a diversified population of sarcoidosis patients and healthy controls as well as subjects with LTBI. We would like to expand test the bioreactivity of sera obtained independently from cases and controls to identify a panel of diagnostic biomarkers/classifiers, which can discriminate between sarcoidosis and healthy controls and latent TB. Furthermore, we will validate the classifiers in independent validation sets and determine whether the discovered biomarkers/classifiers can determine the clinical outcome, especially in the progressive disease course. In Aim 3, we will synthesize the antigen peptides to develop an ELISA to determine the titers of identified antigens. Finally, we test whether these clones are capable of generating granuloma in vitro using latent, healthy controls and sarcoidosis peripheral mononuclear cells. The overall goal is to define the specific antigens initiating granuloma formation in sarcoidosis and how the immunological response to antigen leads to sarcoidosis and latent TB phenotypes.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Lung Diseases Research	000	4	4/24/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $406,509 )
2023	2023	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Lung Diseases Research	000	4	11/23/2022	NON-COMPETING CONTINUATION	$365,859
2023	2023	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Lung Diseases Research	001	4	2/11/2023	NON-COMPETING CONTINUATION	$40,650
														Subtotal = $406,509

Issue Date FY: 2022 ( Subtotal = $447,699 )
2022	2022	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Lung Diseases Research	001	3	6/13/2022	NON-COMPETING CONTINUATION	$44,770
2022	2022	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Lung Diseases Research	000	3	11/10/2021	NON-COMPETING CONTINUATION	$402,929
														Subtotal = $447,699

Issue Date FY: 2021 ( Subtotal = $469,849 )
2021	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Cardiovascular Diseases Research	001	2	5/24/2021	NON-COMPETING CONTINUATION	$46,984
2021	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Cardiovascular Diseases Research	000	2	12/18/2020	NON-COMPETING CONTINUATION	$422,865
														Subtotal = $469,849

Issue Date FY: 2020 ( Subtotal = $503,608 )
2020	2020	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Cardiovascular Diseases Research	000	1	12/13/2019	NEW	$503,608
														Subtotal = $503,608

Grand Total All Awards = $1,827,665

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A novel T7 phage display technology to detect sarcoidosis specific antigens

Award Number: R01HL150474

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/15/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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