Demonstration of Cross-Reactive Antibodies to Smooth Gram-Negative Bacteria in Antiserum to Escherichia coli J5

Baumgartner, J. D.; O’Brien, Terrence X.; Kirkland, Theo N.; Glauser, M. R; Ziegler, Elizabeth

doi:10.1093/infdis/156.1.136

Cited by 34 publications

(13 citation statements)

References 33 publications

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“…Furthermore, recent experimental results suggest that antibodies with the most cross-reactive properties for various gram-negative bacteria are directed against antigenic determinants of the Re LPS, which consists of lipid A and ketodeoxyoctonate, and not against those of E. coli J5 [35]. As recently demonstrated by Stoll et al [32], the titers of antibody to Re LPS in the J5-IVIG preparation used in the present study were not different from those in the IVIG control preparation.…”

Section: Discussionsupporting

confidence: 73%

Treatment of Gram-Negative Septic Shock with Human IgG Antibody to Escherichia coli J5: A Prospective, Double-Blind, Randomized Trial

Calandra¹,

Glauser²,

Schellekens³

et al. 1988

Journal of Infectious Diseases

253

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In a randomized, double-blind, multicenter trial we compared the efficacy of a preparation of human IgG antibody to Escherichia coli with that of a standard IgG preparation (IVIG) for the treatment of gram-negative septic shock. At study entry, patients received a single intravenous dose of 200 mg/kg of body weight (maximal dose, 12 g) of either 15-IVIG or IVIG. Of the 100 patients randomized, 71 (30 receiving 15-IVIG and 41 receiving IVIG) had a documented gram-negative infection. Mortality from gram-negative septic shock was 50% (15 of 30) in 15-IVIG recipients and 49070 (20 of 41) in IVIG recipients. In addition, treatment with 15-IVIG did not reduce the number of systemic complications of shock and did not delay the occurrence of death due to septic shock. Thus we conclude that 15-IVIG was not superior to IVIG in reducing mortality or in reversing gram-negative septic shock.

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Section: Discussionsupporting

confidence: 73%

Treatment of Gram-Negative Septic Shock with Human IgG Antibody to Escherichia coli J5: A Prospective, Double-Blind, Randomized Trial

Calandra¹,

Glauser²,

Schellekens³

et al. 1988

Journal of Infectious Diseases

253

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“…Lipid A is believed to be primarily responsible for the toxic effects of endotoxin. 3 demonstrated that priming of PMNL can be prevented by lipid X, a precursor of lipid A, and by 3-aza-lipid X, a diamino-analogue of lipid X. The latter molecule also exerted an agonist effect, supporting the possibility of a specific receptor-ligand interaction.…”

Section: Discussionmentioning

confidence: 92%

“…The exposure of PMNL to endotoxin in vitro primes the cells to respond to subsequent stimulation by enhanced release of oxygen metabolites and elastase secretion.' [2][3][4][5][6][7][8][9][10][11][12][13][14] This metabolic response of PMNL, the so-called respiratory burst, produces chemiluminescence, which can be amplified and measured in vitro by the addition of luminol.'' PMNL primed by LPS in vivo may even exhibit an increased resistance to infection.…”

Section: Introductionmentioning

confidence: 99%

Inhibition by lipid A-specific monoclonal antibodies of priming of human polymorphonuclear leucocytes by endotoxin

Cornelissen¹,

Kessel

Brouwer

et al. 1991

Journal of Medical Microbiology

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Summary. Exposure to lipopolysaccharide (LPS) primes polymorphonuclear leucocytes (PMNL) for enhanced release of oxygen metabolites after subsequent stimulation. The metabolic response of human PMNL primed with LPS and stimulated with formylmethionyl-leucyl-phenylalanine (FMLP) was measured by chemiluminescence (CL) as a parameter for endotoxic activity. Polymyxin B (PMB) and monoclonal antibodies (MAbs) with specificity for lipid A were tested for inhibition of the priming effect of Re LPS of Salmonella minnesota R595, Rc LPS of Escherichia coli J5 and smooth LPS of E. coli 0 1 11. The CL response of PMNL primed with Re LPS or Rc LPS was higher than that of PMNL primed with smooth LPS. Pre-incubation of rough or smooth LPS with PMB caused dosedependent inhibition of priming of PMNL. Two IgM MAbs, 8-2 and 26-20, which recognise different epitopes on the hydrophobic part of lipid A, also completely prevented priming of PMNL by either rough or smooth LPS. The dose-dependent inhibitory effect of both MAbs was similar to the inhibition by PMB. These results indicate that the binding of MAbs to the hydrophobic part of lipid A is important in blocking lipid A-mediated effects.

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“…Therefore, in the J5 strain the polysaccharide side chains of the endotoxin are missing and the core is exposed. In animals, immunization with LPS from J5, or with whole E coLi J5 bacterial cells, results in high titres of antibody to epitopes of the LPS core (10). Another rough mutant which has been studied for its ability to raise antibodies to the core region is an Re mutant of S minnesoia..…”

Section: J·do Otcomentioning

confidence: 99%

Review and Critique of the Use of Immunoglobulins in Prevention and Treatment of Infection in Critically Ill Patients

Zanetti¹,

Glauser²,

Baumgartner³

1992

Canadian Journal of Infectious Diseases and Medical Microbiolog

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of the use of immunoglobulins in prevention and treatment of infection in critically ill patients. Can J Infect Dis 1992;3(Suppl B):3B-10B. The study of standard intravenous immunoglobulin G (IVIG) preparations as adjunctive therapy in seriously ill patients is motivated by the possible need to: restore immunoglobulin G levels depleted after trauma or surgery; and/or to provide patients with specific antibodies directed against various microorganisms . Whereas no therapeutic efficacy h as been shown in clinical studies with standard IVIG , some data suggest a benefit in prophylactic use. Antisera or IVIG hyperimmune against the biologically active. highly conserved core portion of the endotoxin of Gram-negative bacteria have demonstrated variable degrees of protection in animal models and clinical trials. Two clinical trials using monoclonal antibodies against core lipopolysaccharide have been completed. Only subsets of patients with the Gram-negative sepsis syndrome were protected , but both studies gave discrepant results concerning the type of patients that were reported to benefit from administration of these antibodies. Further studies will be necessary to establish whether application of this therapy can be recommended. Key Words: Critically ill patients, Clinical trial, Immunoglobulin G Revue critique du recours aux immunoglobulines dans Ia prevention et le traitement de !'infection chez les patients gravement maladesLe besoin de restaurer les niveaux d'immunoglobulines G diminuees suite a un traumatisme ou une chirurgie et/ ou Ia necessite d'offrir aux patients des anticorps specifiques diriges contre des microorganismes varies justifient amplement !'etude des preparations d'immunoglobulines intraveineuses standard (IVIG) comme therapie adjuvante chez des patients tres malades. Alors qu'aucune investigation clinique n 'a demontre l'efficacite therapeutique des IVIG, quelques etudes semblent suggerer qu'elles puissent etre uilles comme agent prophylactique. Des antiserums ou des IVIG hyperimmunes diriges contre le "core" de l'endotoxine, Ia portion biologiquement active et Ia mieux conservee de l'endotoxime des bacteries a Gram-n egatif, ont demontre des degres variables de protection dans des modeles animaux et lors d'essais cliniques. Deux essais cliniques portant sur des anticorps monoclonaux diriges contre les "core" lipopolysaccharides ont ete effectues. Seuls des sous-groupes de patients porteurs de syndromes infectieux a Gram-negatif ont ete proteges, mais les deux etudes ont donne des resultats divergents relativement au type de patients qui auraient beneficie de !'administration de ces anticorps. D'autres etudes devront etre entrelprises pour etablir si !'application de ce traitement est recommandable. as a result of several immunological dysfunctions. Decreased levels of immunoglobulin G have been described, especially after trauma and surgery (1). Moreover. neutrophils undergo a decline with respect to chemotaxis, opsonic activity and ability to kill bacteria. In addition , such patients are ex...

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Demonstration of Cross-Reactive Antibodies to Smooth Gram-Negative Bacteria in Antiserum to Escherichia coli J5

Cited by 34 publications

References 33 publications

Treatment of Gram-Negative Septic Shock with Human IgG Antibody to Escherichia coli J5: A Prospective, Double-Blind, Randomized Trial

Treatment of Gram-Negative Septic Shock with Human IgG Antibody to Escherichia coli J5: A Prospective, Double-Blind, Randomized Trial

Inhibition by lipid A-specific monoclonal antibodies of priming of human polymorphonuclear leucocytes by endotoxin

Review and Critique of the Use of Immunoglobulins in Prevention and Treatment of Infection in Critically Ill Patients

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