by We share our experience of a patient with pulmonary alveolar proteinosis who was refractory to plasmapheresis and rituximab despite a significant reduction in the offending antibody. He presented with shortness of breath, fevers, chills, and sweats for 4 months. He was diagnosed with autoimmune PAP based on typical radiology findings, bronchoalveolar fluid analysis, and elevated anti-GM-CSF levels.
Given his limited improvement with whole lung lavage and inhaled GM-CSF therapy, he underwent two series of plasmapheresis. Series one was 5 procedures in 6 days, and series two was 5 procedures in 9 days followed by rituximab. These did not appear to provide any lasting clinical benefit in the year after plasmapheresis despite a marked decrease in serum anti-GM-CSF levels. However, about a year after plasmapheresis, he went into remission and has not required any treatment.
A meta-analysis of granulocyte-macrophage colony-stimulating factor (GM–CSF) antibody treatment for COVID-19 patients
Objective: This meta-analysis aims to assess the efficacy and safety of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies on COVID-19.
Methods: Relevant literatures about GM-CSF antibody treatment in COVID-19 patients were searched from the PubMed, Cochrane Library, Embase, Google scholar, and Baiduscholar databases from the COVID-19 outbreak in December 2019 until 1 January 2021. The primary outcomes included the death, intensive care unit (ICU) admission risk, ventilation requirement, and secondary infection.
Results: A total of 12 eligible literature involving 8979 COVID-19 patients were recruited, and they were divided into experimental group (n = 2673) and control group (n = 6306). Using a random-effect model, it is found that the GM-CSF antibody treatment was associated with a 23% decline of the risk of death [odd’s ratio (OR): 0.34, 95% confidence interval (CI): 0.21-0.56, p < 0.0001] and a 20% enhancement of ventilation (OR: 1.47, 95% CI: 1.19, 1.80, p = 0.0002). GM-CSF antibody treatment did not have a significant correlation to secondary infection and increased risk of ICU admission in COVID-19 patients, which may be attributed to the older age and the length of stay.
Conclusions: Severe COVID-19 patients can benefit from GM-CSF antibodies.
Monoclonal antibodies capable of binding SARS-CoV-2 spike protein receptor-binding motif specifically prevent GM–CSF induction
A severe acute respiratory syndrome (SARS)-like coronavirus 2 (SARS-CoV-2) has recently caused a pandemic COVID-19 disease that infected approximately 94 million and killed more than 2,000,000 people worldwide. Like the SARS-CoV, SARS-CoV-2 also employs a receptor-binding motif (RBM) of its envelope spike protein for binding the host angiotensin-converting enzyme 2 (ACE2) to gain viral entry. Currently, extensive efforts are being made to produce vaccines against a surface fragment of a SARS-CoV-2, such as the spike protein, in order to boost protective antibodies that can inhibit virus-ACE2 interaction to prevent viral entry.
It was previously unknown how spike protein-targeting antibodies would affect innate inflammatory responses to SARS-CoV-2 infections. Here we generated a highly purified recombinant protein corresponding to the RBM of SARS-CoV-2, and used it to screen for cross-reactive monoclonal antibodies (mAbs). We found two RBM-binding mAbs that competitively inhibited its interaction with human ACE2, and specifically blocked the RBM-induced GM-CSF secretion in both human peripheral blood mononuclear cells and murine macrophage cultures. Our findings have suggested a possible strategy to prevent SARS-CoV-2-elicited “cytokine storm,” and revealed a potentially anti-inflammatory and protective mechanism for SARS-CoV-2 spike-based vaccines.
Monoclonal Antibodies Capable of Binding SARS-CoV-2 Spike Protein Receptor Binding Motif Specifically Prevent GM–CSF Induction
A severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) has recently caused a pandemic COVID-19 disease that infected more than 25.6 million and killed 852,000 people worldwide. Like the SARS-CoV, SARS-CoV-2 also employs a receptor-binding motif (RBM) of its envelope spike protein for binding the host angiotensin-converting enzyme 2 (ACE2) to gain viral entry. Currently, extensive efforts are being made to produce vaccines against a surface fragment of a SARS-CoV-2, such as the spike protein, in order to boost protective antibody responses. It was previously unknown how spike protein-targeting antibodies would affect innate inflammatory responses to SARS-CoV-2 infections.
Here we generated a highly purified recombinant protein corresponding to the RBM of SARS-CoV-2, and used it to screen for cross-reactive monoclonal antibodies (mAbs). We found two RBM-binding mAbs that competitively inhibited its interaction with human ACE2, and specifically blocked the RBM-induced GM-CSF secretion in both human monocyte and murine macrophage cultures. Our findings have suggested a possible strategy to prevent SARS-CoV-2-elicited “cytokine storm”, and provided a potentially useful criteria for future assessment of innate immune-modulating properties of various SARS-CoV-2 vaccines.
High Levels of Anti-GM–CSF Antibodies in Deep Infiltrating Endometriosis.
- Endometriosis is a chronic hormono-dependent inflammatory gynecological disease. Endometriosis can be subdivided into three forms: superficial peritoneal implants, endometrioma, and deep infiltrating endometriosis (DIE). Inflammation is a typical feature of endometriosis with overproduction of prostaglandins, chemokines, and cytokines, like granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is a hematopoietic growth factor and immune modulator which belongs to the group of cytokines that actively participate in inflammatory reactions. GM-CSF autoantibodies (Ab) are described in inflammatory diseases such as Crohn disease and ulcerative colitis where high concentrations of anti-GM-CSF Ab are correlated with severity, complications, and relapses.
- We have evaluated the presence of anti-GM-CSF Ab in the serum of 106 patients with endometriosis and 92 controls using a home-made enzyme-linked immunosorbent assay (ELISA) and correlated the results with the form and severity of the disease. We found that anti-GM-CSF Ab level is significantly increased in the sera of patients with endometriosis compared to controls and is associated with the severity of the disease especially in patients with deep endometriosis (p < 0.0001) with the highest number of lesions (p = 0.0034), including digestive involvement (p = 0.0041).
- We also found a correlation between these levels of anti-GM-CSF Ab and the number of lesions in DIE patients (r = 0.913). In this way, searching anti-GM-CSF Ab in endometriosis patient sera could be of value for patient follow-up and put further insight into the role of inflammation and of GM-CSF in endometriosis pathogenesis.
Sperm Antibodies ELISA kit |
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| 55R-IB79154 | Fitzgerald | 96 wells | 528 EUR |
Sperm Antibodies ELISA kit |
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| 55R-IB79155 | Fitzgerald | 96 wells | 578.4 EUR |
Sperm Antibodies ELISA kit |
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| 55R-IB79156 | Fitzgerald | 96 wells | 528 EUR |
Anti-Bovine HMGB1 IgG Antibodies |
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| 7028 | Chondrex | 1 mg/ml x 0.1 ml | 406.26 EUR |
Anti-Bovine HMGB1 IgY Antibodies |
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| 7064 | Chondrex | 1 mg/ml x 0.1 ml | 406.26 EUR |
Bovine mycobacterium bovis antibodies |
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| QY-E60132 | Qayee Biotechnology | 96T | 511.2 EUR |
Rat Cathepsin Antibodies ELISA kit |
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| E02C0695-192T | BlueGene | 192 tests | 1524 EUR |
Rat Cathepsin Antibodies ELISA kit |
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| E02C0695-48 | BlueGene | 1 plate of 48 wells | 624 EUR |
Rat Cathepsin Antibodies ELISA kit |
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| E02C0695-96 | BlueGene | 1 plate of 96 wells | 822 EUR |
Phosphoserine (Set of 6 Antibodies) |
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| abx023806-1Set | Abbexa | 1 Set | 1696.8 EUR |
Dog Cathepsin Antibodies ELISA kit |
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| E08C0695-192T | BlueGene | 192 tests | 1524 EUR |
Dog Cathepsin Antibodies ELISA kit |
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| E08C0695-48 | BlueGene | 1 plate of 48 wells | 624 EUR |
Dog Cathepsin Antibodies ELISA kit |
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| E08C0695-96 | BlueGene | 1 plate of 96 wells | 822 EUR |
Pig Cathepsin Antibodies ELISA kit |
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| E07C0695-192T | BlueGene | 192 tests | 1524 EUR |
Pig Cathepsin Antibodies ELISA kit |
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| E07C0695-48 | BlueGene | 1 plate of 48 wells | 624 EUR |
Pig Cathepsin Antibodies ELISA kit |
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| E07C0695-96 | BlueGene | 1 plate of 96 wells | 822 EUR |
Goat Cathepsin Antibodies ELISA kit |
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| E06C0695-192T | BlueGene | 192 tests | 1524 EUR |
Goat Cathepsin Antibodies ELISA kit |
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| E06C0695-48 | BlueGene | 1 plate of 48 wells | 624 EUR |
Goat Cathepsin Antibodies ELISA kit |
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| E06C0695-96 | BlueGene | 1 plate of 96 wells | 822 EUR |
Anti-GM-CSF/CSF2 Antibody |
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| PB9003 | BosterBio | 100ug/vial | 400.8 EUR |
Anti-GM-CSF/CSF2 Antibody |
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| PA1456 | BosterBio | 100ug/vial | 352.8 EUR |
Human Cathepsin Antibodies ELISA kit |
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| E01C0695-192T | BlueGene | 192 tests | 1524 EUR |
Human Cathepsin Antibodies ELISA kit |
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| E01C0695-48 | BlueGene | 1 plate of 48 wells | 624 EUR |
Human Cathepsin Antibodies ELISA kit |
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| E01C0695-96 | BlueGene | 1 plate of 96 wells | 822 EUR |
Mouse Cathepsin Antibodies ELISA kit |
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| E03C0695-192T | BlueGene | 192 tests | 1524 EUR |
Mouse Cathepsin Antibodies ELISA kit |
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| E03C0695-48 | BlueGene | 1 plate of 48 wells | 624 EUR |
Mouse Cathepsin Antibodies ELISA kit |
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| E03C0695-96 | BlueGene | 1 plate of 96 wells | 822 EUR |
Rabbit Cathepsin Antibodies ELISA kit |
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| E04C0695-192T | BlueGene | 192 tests | 1524 EUR |
Increased Tim-3 expression on TILs during treatment with the Anchored GM–CSF vaccine and anti-PD-1 antibodies is inversely correlated with response in prostate cancer.
Programmed death receptor-1 (PD-1) and T cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) play important roles in tumor immune evasion. PD-1 blockade could produce an effective antitumor effect in many solid tumors except prostate cancer (PCa) because of rare programmed death ligand-1 (PD-L1) expression on PCa cells. Streptavidin (SA)-GM-CSF surface-anchored tumor cell (Anchored GM-CSF) vaccines could increase the number of tumor-infiltrating lymphocytes (TILs) and induce specific antitumor immune responses. The Anchored-GM-CSF vaccine and anti-PD-1 antibodies exerted synergistic effects in mouse models of PCa metastasis. However, the response rate was low due to the presence of other negative regulatory pathways.
Tim-3 expression could be upregulated at resistance to combination therapy with anti-PD-1 antibodies and the Anchored GM-CSF vaccine. Sequential administration of anti-PD-1 and anti-Tim-3 antibodies could further improve the efficacy of the Anchored GM-CSF vaccine therapy, and tumor regression was noted in over 60% of animals. This triple therapy improved the specific cytotoxic activity, proliferation and secretion of CD8+ TILs and reduced the production of tumor-promoting cytokines. These findings indicated that this triple therapy could induce a robust antitumor immune response in mouse models of PCa.
