Binding of cytokines to pharmaceutically prepared human immunoglobulin.

Svenson, Morten; Hansen, Morten Bagge; Bendtzen, Klaus

doi:10.1172/jci116862

Cited by 114 publications

(67 citation statements)

References 45 publications

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“…However, not all autoantibodies are apparently pathogenic, as autoantibodies against various cytokines have been identified in healthy individuals, patients suffering from various immunoinflammatory diseases, and patients treated with the corresponding recombinant cytokines (50 -74). In particular, natural anti-IL-6 autoantibodies have been found in plasma samples from apparently healthy individuals (75)(76)(77)(78)(79)(80)(81) and in patients with rheumatoid arthritis (82), systemic sclerosis (83,84), or alcoholic liver cirrhosis (85). These anti-IL-6 autoantibodies have not been reported to be associated with an increase in susceptibility to bacterial infections.…”

Section: Discussionmentioning

confidence: 99%

Recurrent Staphylococcal Cellulitis and Subcutaneous Abscesses in a Child with Autoantibodies against IL-6

Puel

Pïcard

Lorrot

et al. 2008

The Journal of Immunology

152

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We investigated an otherwise healthy patient presenting two episodes of staphylococcal cellulitis and abscesses, accompanied by high fever and biological signs of inflammation but, paradoxically, with no detectable increase in serum levels of C-reactive protein (CRP), an IL-6-responsive protein synthesized in the liver. Following in vitro activation of whole blood cells from the patient with multiple cytokines, TLR agonists, heat-killed bacteria, and mitogens, we observed a profound and specific impairment of IL-6 secretion. However, the patient’s PBMCs, activated in the same conditions but in the absence of the patient’s plasma, secreted IL-6 normally. The patient’s serum contained high titers of IgG1 autoantibodies against IL-6, which specifically neutralized IL-6 production by control PBMCs as well as IL-6 responses in the human hepatocellular carcinoma cell line Hep3B. These anti-IL-6 autoantibodies were detected over a period of 4 years, in the absence of any other autoantibodies. Our results indicate that these Abs probably prevented an increase in CRP concentration during infection and that impaired IL-6-mediated immunity may have contributed to staphylococcal disease. Patients with severe bacterial infections and low serum CRP concentrations should be tested for anti-IL-6 autoantibodies, especially in the presence of other clinical and biological signs of inflammation.

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Section: Discussionmentioning

confidence: 99%

Recurrent Staphylococcal Cellulitis and Subcutaneous Abscesses in a Child with Autoantibodies against IL-6

Puel

Pïcard

Lorrot

et al. 2008

The Journal of Immunology

152

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“…A third possibility is the inhibitory effect of GG on several cytokines or chemokines. GG preparations or human plasma have been shown to contain specific and neutralizing antibodies against IL-1␣ [46], IL-6 [46], IL-8 [47,48], and MCP-1 [48], and nonspecific inhibitory activity for IL-1␤ [46] or TNF-␣ [46].…”

Section: Discussionmentioning

confidence: 99%

Dramatic decrease of circulating levels of monocyte chemoattractant protein-1 in Kawasaki disease after gamma globulin treatment

Terai

Jibiki

Harada

et al. 1999

Journal of Leukocyte Biology

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“…GM-CSF binding avidity and capacity of purified autoantibodies were determined using the [ 125 I]-GM-CSF binding assay method of Svenson et al 35 Briefly, sera IgG from iPAP patients were isolated by protein-G Sepharose column chromatography (Amersham Biosciences) and quantified as described. Autoantibodies from each person were analyzed separately.…”

Section: Characterization Of Autoantibodiesmentioning

confidence: 99%

“…Autoantibody avidity was also similar to that of autoantibodies directed at other cytokines including IL-1␣ (5.5-11 pM), 39 IL-5 (15 pM), 38 IL-10 (80-351 pM), 38 and IFN-␣ (30 pM). 40 The similarity of ligand binding affinity for these autoantibodies and the natural cytokine receptors 35,[38][39][40][41] suggests that the autoantibodies probably are functionally important in vivo, where they would be expected to effectively compete for ligand binding, thus reducing cytokine receptor occupancy and cytokine signaling. In the case of GM-CSF, this may have pathologic significance with respect to AM function.…”

mentioning

confidence: 99%

High-affinity autoantibodies specifically eliminate granulocyte-macrophage colony-stimulating factor activity in the lungs of patients with idiopathic pulmonary alveolar proteinosis

Uchida¹,

Nakata

Trapnell³

et al. 2003

Blood

212

170

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Deficiency of granulocyte-macrophage colony-stimulating factor (GM-CSF) in mice results in pulmonary alveolar proteinosis (PAP) from impaired surfactant catabolism by alveolar macrophages (AMs). Recently, we have shown that neutralizing anti-GM-CSF autoantibodies develop specifically in patients with idiopathic pulmonary alveolar proteinosis (iPAP). Analogous to murine PAP models, it is plausible that the autoantibodies reduce GM-CSF activity, resulting in AM dysfunction and surfactant accumulation. To examine this hypothesis, we estimated the neutralizing activity of the autoantibodies in the lungs of patients and characterized their biologic properties. GM-CSF bioactivity was completely abrogated in the bronchoalveolar lavage fluid (BALF) of patients with iPAP but not in healthy subjects. Autoantibodies were present in the alveoli in high concentrations and colocalized with GM-CSF. They recognized human GM-CSF with high avidity (K AV ‫؍‬ 20.0 ؎ 7.5 pM) and high specificity, reacting with its superstructure and neutralizing GM-CSF activity to a level 4000 to 58 000 times the levels of GM-CSF normally present in the lung. Although target epitopes varied among patients, GM-CSF amino acids 78 to 94 were consistently recognized. Thus, autoantibodies bind GM-CSF with high specificity and high affinity, exist abundantly in the lung, and effectively block GM-CSF binding to its receptor, inhibiting AM differentiation and function. Our data strengthen the evidence associating anti-GM-CSF autoantibodies with the pathogenesis of this disease.

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Binding of cytokines to pharmaceutically prepared human immunoglobulin.

Abstract: Pharmaceutically prepared IgG, pooled from sera of over 2,000 normal individuals, contained both monomeric and dimeric IgG. Each type of IgG bound '25I-labeled interleukin (IL)-la,

Cited by 114 publications

References 45 publications

Recurrent Staphylococcal Cellulitis and Subcutaneous Abscesses in a Child with Autoantibodies against IL-6

Recurrent Staphylococcal Cellulitis and Subcutaneous Abscesses in a Child with Autoantibodies against IL-6

Dramatic decrease of circulating levels of monocyte chemoattractant protein-1 in Kawasaki disease after gamma globulin treatment

High-affinity autoantibodies specifically eliminate granulocyte-macrophage colony-stimulating factor activity in the lungs of patients with idiopathic pulmonary alveolar proteinosis

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