Clinical significance of anti-GM-CSF antibodies in idiopathic pulmonary alveolar proteinosis

Lin, Fang-Chi; Chang, Geen-Dong; Chern, Ming-Shyan; Chen, Ying-Chu; Chang, Shi-Chuan

doi:10.1136/thx.2005.054171

Cited by 58 publications

(19 citation statements)

References 26 publications

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“…An autoAb response also arose in a subset of patients with metastatic malignant melanoma and renal cell carcinoma who were treated with rhIL-21, but the neutralizing anti-rhIL-21 Abs were not associated with any specific adverse effects (40). Abs to certain cytokines may be involved in various immune-inflammatory diseases such as rheumatoid arthritis, and also certain cancers (64–68), while anti-GM-CSF Abs have been correlated with the severity of pulmonary alveolar proteinosis (69). Abs targeting cytokines, including GM-CSF, IL-2, IL-6, IL-10, IFN-γ and IFN-α, can be detected in the sera of healthy individuals, implying that they are not necessarily harmful (59,70–74).…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies Induced by Chimeric Cytokine-HIV Envelope Glycoprotein Immunogens

Isik

Montfort

Chung

et al. 2014

The Journal of Immunology

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Cytokines are often used as adjuvants to increase the immunogenicity of vaccines as they can improve the immune response and/or direct it into a desired direction. As an alternative to co-delivering antigens and cytokines separately they can be fused into a composite protein, with the advantage that both moieties act on the same immune cells. The HIV-1 envelope glycoprotein (Env) spike, located on the outside of virus particles and the only relevant protein for the induction of neutralizing antibodies (NAbs), is poorly immunogenic. The induction of anti-Env Abs can be improved by coupling Env proteins to co-stimulatory molecules such as a proliferation inducing ligand (APRIL). Here, we evaluated the immunogenicity of chimeric molecules containing uncleaved Env gp140 fused to the species-matched cytokines IL-21 or GM-CSF in rabbits and mice. Each cytokine was either fused to the C-terminus of Env or embedded within Env at the position of the variable loops 1 and 2 (V1V2). The cytokine components of the chimeric Env-GM-CSF and Env-IL-21 molecules were functional in vitro, but none of the Env-cytokine fusion proteins resulted in improved Ab responses in vivo. Both the Env-GM-CSF and the Env-IL-21 molecules induced strong anti-cytokine Ab responses, in both test species. These autoimmune responses were independent of the location of the cytokine in the chimeric Env molecules; in that they were induced by cytokines inserted within the V1V2 of Env or fused to its Ct. The induction of undesired autoimmune responses should be considered when using cytokines as co-stimulatory molecules in fusion proteins.

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Section: Discussionmentioning

confidence: 99%

Autoantibodies Induced by Chimeric Cytokine-HIV Envelope Glycoprotein Immunogens

Isik

Montfort

Chung

et al. 2014

The Journal of Immunology

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“…132, 133 Lin et al found a significant correlation between BALF (but not the serum GM-CSF antibodies) and other severity indicators, and subsequent requirement of therapeutic lung lavage. 134 This could be related to compartmentalization leading to differences in BALF and serum antibody levels. Similarly, Seymour et al found no relationship between the serum anti-GM-CSF antibody concentration and disease severity or predicting the response to GM-CSF therapy.…”

Section: Granulocyte Macrophage Colony Stimulating Factor Autoantibodmentioning

confidence: 99%

Pulmonary Alveolar Proteinosis

Khan

Agarwal

2011

Respir Care

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“…The authors also reported that the patient with PAP associated with chronic hydrogen fluoride inhalation (4). In the BAL or serum, anti-GM-CSF antibody measurement is useful for secondary PAP diagnosis and levels of anti-GM-CSF antibodies correlated with the severity of PAP (11). In one patient with PAP related to indium-tin oxide exposure, elevated levels of antibodies to GM-CSF were noted (12).…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Alveolar Proteinosis and Tracheal Stenosis After Exposure to Fire and Fire Extinghuisher

Çörtük¹,

O²,

Abbaslı³

et al. 2016

Respir Case Rep

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Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of acellular surfactant lipids and proteins within the alveoli. Idiopathic PAP accounts for about 90% of all patients. Secondary PAP factors include insecticides, inorganic dusts such as silica, hematological malignancies, Human Immunodeficiency Virus infection, leflunomide, toxic gas inhalation, various industrial exposures to aluminum-and metal oxide-containing dusts and clinical conditions. Herein, we present a case of pulmonary alveolar proteinosis and tracheal stenosis secondary to exposure to fire and fire extinguisher.

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Clinical significance of anti-GM-CSF antibodies in idiopathic pulmonary alveolar proteinosis

Cited by 58 publications

References 26 publications

Autoantibodies Induced by Chimeric Cytokine-HIV Envelope Glycoprotein Immunogens

Autoantibodies Induced by Chimeric Cytokine-HIV Envelope Glycoprotein Immunogens

Pulmonary Alveolar Proteinosis

Pulmonary Alveolar Proteinosis and Tracheal Stenosis After Exposure to Fire and Fire Extinghuisher

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