GM-CSF antibody levels and disease severity in autoimmune pulmonary alveolar proteinosis: a correlation analysis_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

SHI Shenyun ¹ , XIN Xiaoyan ² ,  XIAO Yonglong ¹

1. Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P. R. China;
2. Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P. R. China;

Corresponding?author：

XIAO Yonglong, Email: yonglong11a@163.com

Keywords：

Pulmonary alveolar proteinosis; granulocyte-macrophage colony-stimulating factor antibody; disease severity; biomarker

DOI：

10.7507/1671-6205.202604064

Video：

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Objective To investigate the correlation between granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody levels and disease severity in autoimmune pulmonary alveolar proteinosis (PAP). Methods A retrospective analysis was conducted on 18 patients with autoimmune PAP. Serum GM-CSF antibody levels were measured, and pulmonary function [diffusion capacity of the lung for carbon monoxide as a percentage of predicted value (D_LCO%pred) and forced vital capacity as a percentage of predicted value(FVC%pred)], oxygenation index, high-resolution CT imaging scores (percentage of ground-glass opacification/consolidation in each lobe and proportion of Hounsfield unit partitions) were evaluated. Spearman correlation analysis and comparison between high- and low-antibody groups were performed. Results A total of 18 patients were enrolled, with GM-CSF antibody levels ranging from 66.2 to 445 U/mL. Correlation analysis showed that GM-CSF antibody levels were not significantly correlated with D_LCO%pred, FVC%pred, oxygenation index, disease severity score, or the percentage of whole-lung ground-glass opacification/consolidation. No statistically significant differences were observed in any severity indicators between the high-antibody group (>400 U/mL) and the moderate-to-low antibody group (≤400 U/mL) (P>0.05). Conclusions Although GM-CSF antibody level is a key diagnostic marker for autoimmune PAP, it cannot serve as a reliable biomarker for assessing disease severity. In clinical practice, judging disease severity based on antibody titer should be avoided.

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14.	Ataya A, Knight V, Carey BC, et al. The role of GM-CSF autoantibodies in infection and autoimmune pulmonary alveolar proteinosis: a concise review[J]. Front Immunol, 2021, 12: 752856.
15.	Trapnell BC, Inoue Y, Bonella F, et al. Phase 3 trial of inhaled molgramostim in autoimmune pulmonary alveolar proteinosis[J]. N Engl J Med, 2025, 393(8): 764-773.
16.	Campo I, Carey BC, Paracchini E, et al. Inhaled recombinant GM-CSF reduces the need for whole lung lavage and improves gas exchange in autoimmune pulmonary alveolar proteinosis patients[J]. Eur Respir J, 2024, 63(1): 2301233.
17.	McCarthy C, Carey BC, Trapnell BC. Autoimmune Pulmonary Alveolar Proteinosis[J]. Am J Respir Crit Care Med, 2022, 205(9): 1016-1035.

1. Jouneau S, Ménard C, Lederlin M. Pulmonary alveolar proteinosis[J]. Respirology, 2020, 25(8): 816-826.
2. Kumar A, Abdelmalak B, Inoue Y, et al. Pulmonary alveolar proteinosis in adults: pathophysiology and clinical approach[J]. Lancet Respir Med, 2018, 6(7): 554-565.
3. Inoue Y, Trapnell BC, Tazawa R, et al. Japanese Center of the Rare Lung Diseases Consortium[J]. Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan[J]. Am J Respir Crit Care Med, 2008, 177(7): 752-762.
4. Uchida K, Nakata K, Trapnell BC, et al. High-affinity autoantibodies specifically eliminate granulocyte-macrophage colony-stimulating factor activity in the lungs of patients with idiopathic pulmonary alveolar proteinosis[J]. Blood, 2004, 103(3): 1089-1098.
5. Kitamura T, Uchida K, Tanaka N, et al. Serological diagnosis of idiopathic pulmonary alveolar proteinosis[J]. Am J Respir Crit Care Med, 2000, 162: 658-662.
6. Tazawa R, Ueda T, Abe M, et al. Inhaled GM-CSF for Pulmonary Alveolar Proteinosis[J]. N Engl J Med, 2019, 381(10): 923-932.
7. Bonella F, Bauer PC, Griese M, et al. Pulmonary alveolar proteinosis: new insights from a single-center cohort of 70 patients[J]. Respir Med, 2011, 105(12): 1908-1916.
8. Bonfield TL, Kavuru MS, Thomassen MJ. Anti-GM-CSF titer predicts response to GM-CSF therapy in pulmonary alveolar proteinosis[J]. Clin Immunol, 2002, 105(3): 342-350.
9. Nei T, Urano S, Itoh Y, et al. Light chain (κ/λ) ratio of GM-CSF autoantibodies is associated with disease severity in autoimmune pulmonary alveolar proteinosis[J]. Clin Immunol, 2013, 149(3): 357-364.
10. Shi SY, Zou RY, Chen LL, et al. Quantitative chest CT assessment of pulmonary alveolar proteinosis with deep learning: a real-world longitudinal study[J]. Quant Imaging Med Surg, 2022, 12(12): 5394-5403.
11. Trapnell BC, Inoue Y, Bonella F, et al. Inhaled molgramostim therapy in autoimmune pulmonary alveolar proteinosis[J]. N Engl J Med, 2020, 383(17): 1635-1644.
12. Suzuki T, Sakagami T, Rubin BK, et al. Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA[J]. J Exp Med, 2008, 205(12): 2703-2710.
13. Sakagami T, Uchida K, Suzuki T, et al. Human GM-CSF autoantibodies and reproduction of pulmonary alveolar proteinosis[J]. N Engl J Med, 2009, 361(27): 2679-2681.
14. Ataya A, Knight V, Carey BC, et al. The role of GM-CSF autoantibodies in infection and autoimmune pulmonary alveolar proteinosis: a concise review[J]. Front Immunol, 2021, 12: 752856.
15. Trapnell BC, Inoue Y, Bonella F, et al. Phase 3 trial of inhaled molgramostim in autoimmune pulmonary alveolar proteinosis[J]. N Engl J Med, 2025, 393(8): 764-773.
16. Campo I, Carey BC, Paracchini E, et al. Inhaled recombinant GM-CSF reduces the need for whole lung lavage and improves gas exchange in autoimmune pulmonary alveolar proteinosis patients[J]. Eur Respir J, 2024, 63(1): 2301233.
17. McCarthy C, Carey BC, Trapnell BC. Autoimmune Pulmonary Alveolar Proteinosis[J]. Am J Respir Crit Care Med, 2022, 205(9): 1016-1035.

Chinese Journal of Respiratory and Critical Care Medicine

Latest ArticlesGM-CSF antibody levels and disease severity in autoimmune pulmonary alveolar proteinosis: a correlation analysis

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