Cryptococcus gattii Infection as the Major Clinical Manifestation in Patients with Autoantibodies Against Granulocyte–Macrophage Colony-Stimulating Factor

Wang, Shang‐Yu; Lo, Yu-Fang; Shih, Han-Po; Ho, Mao‐Wang; Yeh, Chun‐Fu; Peng, Jhan-Jie; Ting, He; Lin, Kuo‐Hsi; Huang, Wen-Chi; Chen, Yi‐Chun; Chiu, Yu‐Hsin; Hsu, Chin Wang; Tseng, Yu‐Ting; Wang, Lih-Shinn; Lei, Wei‐Yi; Lin, Chen‐Yuan; Aoh, Yu; Chou, Chia-Huei; Wu, Tsai-Yi; Ding, Jing-Ya; Lo, Chia-Chi; Lin, You-Ning; Tu, Kun-Hua; Lei, Wei‐Te; Kuo, Chen-Yen; Chi, Chih-Yu; Ku, Cheng-Lung

doi:10.1007/s10875-022-01341-2

Cited by 10 publications

(13 citation statements)

References 45 publications

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“…Ongoing investigations in other disease states and infections [ e.g. nontuberculosis mycobacteria ( 252 ), pulmonary aspergillus ( 176 ), C. gattii cryptococcosis ( 186 ), and respiratory syncytial virus ( 112 , 253 )] further highlight the wide potential role of immunomodulatory agents such as sargramostim. Specifically, for neurodegenerative diseases, early investigations suggest innate immune modulation and illustrate GM-CSF/sargramostim potential to ameliorate symptoms and pathology of Alzheimer’s and Parkinson’s Diseases, among others ( 33 – 36 ).…”

Section: Discussionmentioning

confidence: 99%

“…Prospective immunophenotyping and/or patient stratification based on blood cell counts, immune function assays, cytokine levels, GM-CSF auto-antibody levels [ e.g. , in Cryptococcus gattii cryptococcosis ( 186 )], or other markers of inflammation would help define optimal timing of drug administration ( e.g. , sargramostim) to prevent organ failure and death ( 9 ).…”

Section: Immune Responses To Infections and Risk Of Gm-csf Insufficiencymentioning

confidence: 99%

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Recombinant GM-CSF for diseases of GM-CSF insufficiency: Correcting dysfunctional mononuclear phagocyte disorders

Lazarus

Pitts²,

Wang

et al. 2023

Front. Immunol.

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IntroductionEndogenous granulocyte-macrophage colony-stimulating factor (GM-CSF), identified by its ability to support differentiation of hematopoietic cells into several types of myeloid cells, is now known to support maturation and maintain the metabolic capacity of mononuclear phagocytes including monocytes, macrophages, and dendritic cells. These cells sense and attack potential pathogens, present antigens to adaptive immune cells, and recruit other immune cells. Recombinant human (rhu) GM-CSF (e.g., sargramostim [glycosylated, yeast-derived rhu GM-CSF]) has immune modulating properties and can restore the normal function of mononuclear phagocytes rendered dysfunctional by deficient or insufficient endogenous GM-CSF.MethodsWe reviewed the emerging biologic and cellular effects of GM-CSF. Experts in clinical disease areas caused by deficient or insufficient endogenous GM-CSF examined the role of GM-CSF in mononuclear phagocyte disorders including autoimmune pulmonary alveolar proteinosis (aPAP), diverse infections (including COVID-19), wound healing, and anti-cancer immune checkpoint inhibitor therapy.ResultsWe discuss emerging data for GM-CSF biology including the positive effects on mitochondrial function and cell metabolism, augmentation of phagocytosis and efferocytosis, and immune cell modulation. We further address how giving exogenous rhu GM-CSF may control or treat mononuclear phagocyte dysfunction disorders caused or exacerbated by GM-CSF deficiency or insufficiency. We discuss how rhu GM-CSF may augment the anti-cancer effects of immune checkpoint inhibitor immunotherapy as well as ameliorate immune-related adverse events.DiscussionWe identify research gaps, opportunities, and the concept that rhu GM-CSF, by supporting and restoring the metabolic capacity and function of mononuclear phagocytes, can have significant therapeutic effects. rhu GM-CSF (e.g., sargramostim) might ameliorate multiple diseases of GM-CSF deficiency or insufficiency and address a high unmet medical need.

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Section: Discussionmentioning

confidence: 99%

Section: Immune Responses To Infections and Risk Of Gm-csf Insufficiencymentioning

confidence: 99%

Recombinant GM-CSF for diseases of GM-CSF insufficiency: Correcting dysfunctional mononuclear phagocyte disorders

Lazarus

Pitts²,

Wang

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…A serial survey that included autoimmune profiles (antinuclear antibody, rheumatoid factor, anti-neutrophil cytoplasmic antibody, anti–double stranded DNA, complement component 3, and complement component 4), HIV-1/2 antibodies, and free HIV-1 p24 antigen (HIV-1/2 Ag/Ab Comb test; Abbott Laboratories, https://www.abbott.com ) all showed negative results, but the result for the anti-granulocyte-macrophage colony-stimulating factor autoantibody (anti-GM-CSF AAb) was positive (titer 0.84), as measured using ELISA as previously described ( 4 ).…”

mentioning

confidence: 99%

“…Approximately 20% of the HIV-infected tested population had cryptococcal meningitis caused by C. tetragattii in Zimbabwe ( 6 ). In addition, anti-GM-CSF AAb has been detected in immunocompetent patients with C. gattii infection, as well as those with C. neoformans infection ( 4 ).…”

mentioning

confidence: 99%