Evidence map›Paper›PMID 41345615›Full record

ArticleRespiratory research2025

Signal regulating proteins (SIRPs) participate in sarcoidosis granuloma formation by promoting immune cell aggregation.

Marc A Judson, Mark W Julian, Llewellyn Foulke, Sandip Panicker, Soe H Arker, Paul J Feustel, Graham Parry, Sabahattin Bicer, Elliott D Crouser

Abstract read
In one paragraph

Article in Respiratory research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Marc A JudsonDivision of Pulmonary and Critical Care Medicine, Albany Medical College, Albany, NY, USA.
Mark W JulianDivision of Pulmonary, Critical Care and Sleep Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Room 405c; 473 West 12th Ave, Columbus, OH, 43210, USA.
Llewellyn FoulkeDepartment of Pathology, Albany Medical College, Albany, NY, USA.
Sandip PanickerElectra Therapeutics, Inc, South San Francisco, CA, USA.
Soe H ArkerDepartment of Pathology, Albany Medical College, Albany, NY, USA.
Paul J FeustelDepartment of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY, USA.
Graham ParryElectra Therapeutics, Inc, South San Francisco, CA, USA.
Sabahattin BicerDivision of Pulmonary, Critical Care and Sleep Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Room 405c; 473 West 12th Ave, Columbus, OH, 43210, USA.
Elliott D CrouserDivision of Pulmonary, Critical Care and Sleep Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Room 405c; 473 West 12th Ave, Columbus, OH, 43210, USA. Elliott.Crouser@osumc.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSignal regulatory protein alpha (SIRPα) is an important regulator of innate and adaptive immune responses by promoting T cell and macrophage activation and macrophage adhesion (multi-nucleated giant cell formation) while preventing phagocytic cell death to sustain inflammatory responses.

methodsWe determined whether SIRPα is expressed in sarcoidosis tissue and whether ELA026, a humanized SIRP-blocking Ab, suppresses sarcoidosis granuloma formation by attenuating inflammation, promoting cell death, and suppressing adhesion during granuloma formation.

resultsBased upon immunohistochemistry, SIRPα stained in greater abundance in giant cells, monocytes, macrophages and dendritic cells in sarcoidosis lung tissue than in normal lung, lung cancer, non-granulomatous lung diseases and non-sarcoidosis granulomatous diseases. All these differences were statistically significant except for non-sarcoidosis granulomatous lung diseases. We then leveraged an ex vivo human granuloma model, wherein PBMCs from sarcoidosis patients are activated to form granulomas within 7 days, to determine whether ELA026 attenuated granuloma formation, based upon MIPAR image analysis, and associated cytokine responses. A matching isotype antibody (ELA099) that does not bind SIRPs was a negative control; prednisone was a positive control. As hypothesized, pre-treatment (day 0) or post-treatment (day 4) with ELA026 or prednisone (not ELA099) caused dose-dependent suppression of sarcoidosis granuloma formation by day 7. Unexpectedly, ELA026 only modestly reduced TNFα production when used as a pre-treatment and did not suppress IL-1β release or promote cell death, as reflected by no LDH release.

conclusionsSIRPα is robustly expressed in monocyte/macrophage lineages within human sarcoidosis tissues, and inhibition of SIRPs (ELA026) suppresses sarcoidosis granuloma formation by preventing macrophage adhesion/aggregation.

Indexed as

Cell AggregationGranulomaGranuloma, Respiratory TractLungReceptors, ImmunologicSarcoidosisSarcoidosis, PulmonaryAntibodies, Monoclonal, HumanizedAntigens, DifferentiationCells, CulturedFemaleHumansMaleAntibodies, Monoclonal, HumanizedAntigens, DifferentiationReceptors, ImmunologicSIRPA protein, human

Identifiers

PMID41345615
PMCPMC12781305

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.