The Pathogenic Role of Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in the Nocardiosis with the Central Nervous System Involvement

Yu-Fang Lo^#¹, Shang-Yu Wang^#^{1

2}, Yi-Hui Wu³, Mao-Wang Ho⁴, Chun-Fu Yeh^{1

5}, Tsai-Yi Wu¹, Jhan-Jie Peng¹, You-Ning Lin^{1

6}, Jing-Ya Ding^{1

6}, Han-Po Shih^{1

6}, Chia-Chi Lo^{1

6}, Yu-Pei Chan¹, Cheng-Shyuan Rau⁷, Chen-Yen Kuo^{1

8}, Kun-Hua Tu^{1

9}, Wei-Te Lei^{1

10

11}, Yi-Chun Chen¹², Cheng-Lung Ku^{13

14

15

16}

Affiliations

¹ Laboratory of Human Immunology and Infectious Diseases, Graduate Institute of Clinical Medical Sciences, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist, Taoyuan City, 33302, Taiwan.
² Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
³ Division of Infectious Diseases, Department of Internal Medicine, PingTung Christian Hospital and Future clinic, PingTung, Taiwan.
⁴ Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
⁵ Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Centre, Taoyuan, Taiwan.
⁶ Center for Molecular and Clinical and Immunology, Chang Gung University, Taoyuan, Taiwan.
⁷ Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
⁸ Division of Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁹ Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
¹⁰ Section of Immunology, Rheumatology, and Allergy Department of Pediatrics, Hsinchu Mackay Memorial Hospital, Hsinchu City, Taiwan.
¹¹ Section of Immunology, Rheumatology, and Allergy Department of Pediatrics, Hsinchu Municipal Mackay Children's Hospital, Hsinchu City, Taiwan.
¹² Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Rd., Niaosong Dist, Kaohsiung City, 833401, Taiwan. rm8901083@gmail.com.
¹³ Laboratory of Human Immunology and Infectious Diseases, Graduate Institute of Clinical Medical Sciences, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist, Taoyuan City, 33302, Taiwan. clku@cgu.edu.tw.
¹⁴ Center for Molecular and Clinical and Immunology, Chang Gung University, Taoyuan, Taiwan. clku@cgu.edu.tw.
¹⁵ Division of Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan. clku@cgu.edu.tw.
¹⁶ Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. clku@cgu.edu.tw.

^# Contributed equally.

PMID: 39133333
DOI: 10.1007/s10875-024-01775-w

The Pathogenic Role of Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in the Nocardiosis with the Central Nervous System Involvement

Yu-Fang Lo et al. J Clin Immunol. 2024.

. 2024 Aug 12;44(8):176.

doi: 10.1007/s10875-024-01775-w.

Authors

Affiliations

¹ Laboratory of Human Immunology and Infectious Diseases, Graduate Institute of Clinical Medical Sciences, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist, Taoyuan City, 33302, Taiwan.
² Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
³ Division of Infectious Diseases, Department of Internal Medicine, PingTung Christian Hospital and Future clinic, PingTung, Taiwan.
⁴ Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
⁵ Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Centre, Taoyuan, Taiwan.
⁶ Center for Molecular and Clinical and Immunology, Chang Gung University, Taoyuan, Taiwan.
⁷ Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
⁸ Division of Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁹ Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
¹⁰ Section of Immunology, Rheumatology, and Allergy Department of Pediatrics, Hsinchu Mackay Memorial Hospital, Hsinchu City, Taiwan.
¹¹ Section of Immunology, Rheumatology, and Allergy Department of Pediatrics, Hsinchu Municipal Mackay Children's Hospital, Hsinchu City, Taiwan.
¹² Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Rd., Niaosong Dist, Kaohsiung City, 833401, Taiwan. rm8901083@gmail.com.
¹³ Laboratory of Human Immunology and Infectious Diseases, Graduate Institute of Clinical Medical Sciences, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist, Taoyuan City, 33302, Taiwan. clku@cgu.edu.tw.
¹⁴ Center for Molecular and Clinical and Immunology, Chang Gung University, Taoyuan, Taiwan. clku@cgu.edu.tw.
¹⁵ Division of Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan. clku@cgu.edu.tw.
¹⁶ Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. clku@cgu.edu.tw.

^# Contributed equally.

PMID: 39133333
DOI: 10.1007/s10875-024-01775-w

Abstract

Purpose: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients.

Methods: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients.

Results: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated.

Conclusion: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.

Keywords: Cryptococcus gattii; Anti-GM-CSF autoantibody; Central nervous system infection; Nocardiosis; Pulmonary alveolar proteinosis.

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References

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The Pathogenic Role of Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in the Nocardiosis with the Central Nervous System Involvement

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The Pathogenic Role of Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in the Nocardiosis with the Central Nervous System Involvement

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