A bioluminescent inhibition immunoassay for detecting GM-CSF inhibitory activity in serum
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2026
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Abstract
INTRODUCTION: Autoantibodies against Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) are the cause of autoimmune pulmonary alveolar proteinosis (aPAP). They are also found in the serum/plasma of previously immunocompetent patients with disseminated Cryptococcus spp. infection (typically spp. gattii) and disseminated Nocardia spp. infection. METHODS: Detection of this autoantibody is generally performed through an antibody binding assay, followed by a live-cell based pSTAT5 neutralisation to confirm functional significance of detected autoantibodies. The requirement for a live-cell based assay increases the technical difficulty of diagnosis and means that this testing is generally only offered in specialist research centres. We report a bioluminescent immunoassay (BLIA) platform which accurately detects inhibition of GM-CSF detection in serum. The BLIA method has previously been described in detail to detect anti-cytokine autoantibodies against IFNγ. The BLIA platform was able to distinguish 24 blinded disease control samples with 100% accuracy when compared to gold standard testing. We sought referrals for patients with aPAP, Cryptococcus spp. infection and Nocardia spp. infection to test the performance of this assay. RESULTS: Positive results were seen in 100% of patients with clinically confirmed aPAP and a proportion of patients with disseminated Cryptococcus or Nocardia spp. infection. CONCLUSION: The BLIA is technically simple, rapid and easily automatable and could be easily employed in a diagnostic laboratory. The performance characteristics of the BLIA result in rapid and accurate screening of patients with these uncommon autoantibody mediated conditions, allowing for quick diagnosis and referral for specialist management.
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| Authors | Peter Bradhurst, Alex Stoyanov, Lindsey B Rosen, Steven M Holland, Thomas Guy, Nicolás Urriola |
| Journal | Clinical & Experimental Immunology |
| Year | 2026 |
| DOI |
10.1093/cei/uxag027
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| URL | |
| Keywords | Keywords not found |
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