{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:43:09Z","timestamp":1787064189013,"version":"build-2736575974"},"reference-count":34,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"unspecified","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NIH","award":["R01HL162955"],"award-info":[{"award-number":["R01HL162955"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,4,7]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Sarcoidosis is a heterogeneous granulomatous disease with highly variable clinical trajectories, yet no validated biomarkers exist to distinguish progressive sarcoidosis (P-sarcoidosis) from non-progressive disease (NP-sarcoidosis). This lack of tractable biomarkers limits early risk stratification and impedes therapeutic decision-making. Preliminary data from our group suggest that P-sarcoidosis and NP-sarcoidosis may be differentiated by blood-derived and peripheral blood mononuclear cell (PBMC)-derived molecular signatures, as well as ex vivo granuloma biogenesis in response to putative disease-causing antigens. This protocol describes a multi-omic study aimed at identifying mechanistically grounded, clinically translatable biomarkers that distinguish P-sarcoidosis from NP-sarcoidosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We will perform an integrative proteomic and transcriptomic analysis across three biological compartments: ex vivo granuloma model, PBMCs and plasma. Participants with clinically adjudicated P-sarcoidosis or NP-sarcoidosis will provide blood samples for multi-omic profiling. P-sarcoidosis versus NP-sarcoidosis phenotype will be assessed based on changes in spirometry, diffusing capacity for carbon monoxide, chest radiography and need for treatment for pulmonary symptoms. Patient-reported outcomes will also be recorded. Data-driven computational approaches will be used to identify molecular pathways associated with granuloma formation and disease persistence and to develop a classifier that distinguishes P-sarcoidosis from NP-sarcoidosis. Rigorous internal validation, feature-selection procedures and statistical controls for high-dimensional data will be applied. Candidate biomarkers emerging from multi-compartment integration will be prioritised based on biological coherence, reproducibility and clinical feasibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study protocol has been approved by the Biomedical Research Alliance of New York, serving as a single Institutional Review Board (IRB) for the project (IRB # 23\u201302-503), as well as at National Jewish Health (IRB# HS-4091), University of Minnesota (STUDY00020121\/SITE00002051) and The Ohio State University (IRB# 2023X0140). All participants will provide informed consent prior to enrolment. Results will be disseminated through peer-reviewed publications, scientific conferences and presentations to patients and advocacy groups. De-identified datasets and analytic workflows will be shared in accordance with institutional policies and data-sharing agreements.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-119604","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:30:24Z","timestamp":1777480224000},"page":"e119604","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular characterisation of progressive pulmonary sarcoidosis: protocol for a longitudinal multi-centre study to develop peripheral blood circulating biomarkers for predicting pulmonary sarcoidosis progression"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1294-6181","authenticated-orcid":false,"given":"Maneesh","family":"Bhargava","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep, The Ohio State University, Columbus, Ohio, 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