Enhanced survival in Pseudomonas aeruginosa septicemia associated with high levels of circulating antibody to Escherichia coli endotoxin core.

Pollack, Matthew; A, Huang; Prescott, Richard K.; Young, Lowell S.; Hunter, Kenneth W.; Cruess, David F.; Tsai, Chao-Ming

doi:10.1172/jci111150

Cited by 102 publications

(35 citation statements)

References 27 publications

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“…However, clinical data suggesting that cross-protective antibodies are of the IgM class are limited to a study in patients with Pseudomonas aeruginosa bacteremia. In these patients, core-specific antibodies of the IgM isotype predicted survival more significantly than those of the IgG isotype [36]. Yet, in contrast to these results, preliminary data in the present study failed to demonstrate a correlation between survival and core-specific antibodies of the IgG or IgM class (J. D. Baumgartner, personal communication).…”

Section: Discussioncontrasting

confidence: 94%

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: Discussioncontrasting

confidence: 94%

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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“…Furthermore, we have found that the majority of these antibodies are type-specific for the LPS from the immunizing rough mutant. A similar conclusion has also been drawn from experiments using IHA to measure antibody to LPS from rough bacteria [29]. To improve the detection of cross-reactive antibodies in polyclonal antisera, we have used several techniques.…”

Section: Resultsmentioning

confidence: 60%

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

Baumgartner

O’Brien

Kirkland

et al. 1987

Journal of Infectious Diseases

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We investigated the discrepancy between the broad cross-protection against gram-negative infections afforded by antiserum to Escherichia coli J5 and its apparently narrow crossreactivity in vitro. Rabbits immunized with J5 bacteria produced antibodies to both the J5 lipopolysaccharide (LPS; titer by ELISA, 1:60,0(0) and LPS from the Re mutant of Salmonella minnesota (i.e., to the ketodeoxyoctonate [KDO] and lipid A determinants; titer, 1:3,2(0). In highly diluted antiserum, titers of antibody to J 5 LPS were reduced by 28070-41% after adsorption with seven strains of smooth gram-negative bacteria and by only 4% after adsorption with the Re mutant. Smooth gram-negative bacteria adsorbed virtually all antibody to Re LPS. Therefore, rabbit antiserum to J 5 contains type-specific antibodies to core determinants distal to KDO that can obscure highly cross-reactive antibodies to lipid A-KDO in vitro. Cross-reactive antibodies are demonstrable byadsorption with whole bacteria at limiting concentrations of antibody.Endotoxins (lipopolysaccharides [LPS)) from rough mutants contain lipid A (the toxic moiety of the molecule) and some sugars from the core region, but, in contrast to LPS from smooth bacteria, they lack the very immunogenic oligosaccharide side chains [1,2]. Although these 0 side chains exhibit wide antigenic variation, the LPS core region is conserved among gram-negative bacteria. Immunizing animals with smooth gram-negative bacteria does not stimulate the formation of cross-protective antibody, despite the fact that LPS from these smooth bacteria also contain the common determinants of core LPS. This observation has been explained by either steric hindrance (because the core LPS is surrounded by side chains) or poor immunogenicity of core LPS compared with the immunogenic dominance of side chains.Immunization with LPS from rough mutants stimulates high titers of antibody to determinants of LPS core, and the potential of such antisera to protect against a wide variety of unrelated, smooth gram-negative bacteria or endotoxins (LPS) has been established in numerous experimental models [3][4][5][6][7][8][9][10][11][12][13].Received for publication 3 July 1986, and in revised form 9 February 1987. This study was supported by grant AI-I0108 from the National Institute of Allergy and Infectious Diseases.Please address requests for reprints to Dr. J. D. Baumgartner, Division of Infectious Diseases, Department of Internal Medicine, CHUV, CH-1011 Lausanne, Switzerland. 136Clinical studies have shown that antiserum to Escherichia coli J5 increased the survival of patients who had gram-negative bacteremia [14] and prevented shock due to gram-negative infections in high-risk surgical patients [15].Antisera raised to rough mutants have crossprotective activity that we and others have attributed to the presence of antibodies to core LPS [1,11,16], but cross-reaction between antibody to rough mutants and smooth gram-negative bacteria has been difficult to demonstrate in vitro. Immunofluorescent tests using whole smooth bac...

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“…Thus, the LPS of these mutants is composed only of lipid A and various core sugars. Tworough strains have been widely used to detect cross-reactive antibodies in patients; one of these is the Re mutant of Salmonella minnesota used by McCabe et al [8] and the other is the 15 mutant of Escherichia coli 0111 used by Pollack et al [9,10]. McCabe et al [8] have shown that the survival of patients with gram-negative bacteremia was related to their titers of antibody to the core glycolipid present at the onset of bacteremia (table 2).…”

Section: Relation Between Outcome Of Infection In the Critically III mentioning

confidence: 99%

“…Subsequently, when measuring antibodies in the same sera by immunofluorescence, Zinner et al [11] found that survival was significantly related to the titers of a-specific IgG antibodies but not to the titers of a-specific IgM antibodies. Studies by Pollack et al [9,10] have concentrated on patients with Pseudomonas aeruginosa septicemia. In accordance with the observation by McCabe et al [8], Pollack and Young [9] observed a similar relation between survival of patients with R aeruginosa septicemia and titers of a-specific antibodies measured by indirect hemagglutination with purified R aeruginosa LPS.…”

Section: Relation Between Outcome Of Infection In the Critically III mentioning

confidence: 99%

“…At present, the only established uses for passive immunotherapy in the field of infectious diseases are as replacement therapy in primary humoral immunodeficiencies and as prophylaxis for some viral infections and diseases caused by bacterial exotoxins (table 1). This paper was presented at a symposium, "Controversies in the Diagnosis and Management of Infectious Diseases," held in Laguna Niguel, California, November [10][11][12]1985, which was sponsored by the Division of Infectious Diseases/Epidemiology of Columbia University and funded by an educational grant from Smith Kline &French Laboratories and Fujisawa/SmithKline Corporation.…”

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confidence: 99%

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Controversies in the Use of Passive Immunotherapy for Bacterial Infections in the Critically Ill Patient

Baumgartner

Glauser

1987

Clinical Infectious Diseases

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Several preparations of standard immunoglobulins for intravenous use have been tested as adjunctive therapy for bacterial infections in premature neonates and in critically ill adults after major surgery, trauma, and burn. The use of intravenous immunoglobulins in these settings is controversial because the efficacy and cost-effectiveness of this treatment are still not definitivelyestablished. Specificpreparations of immunoglobulins against Pseudomonas aeruginosa for intramuscular administration have shown promising efficacy, and 'preparations for intravenous administration are now under investigation. Cross-protection against a wide range of gram-negative infections has been attempted by the administration of antiserum to the core glycolipid of lipopolysaccharide prepared from volunteers immunized with the J5 mutant of Escherichia coli 0111. Treatment with this preparation improved the survival rate of patients with gram-negative bacteremia and, when administered prophylactically to high-risk surgical patients, prevented shock and death related to gram-negative infections. The mechanism of protection of the J5 antiserum is not clearly understood because of our inability to measure the actual protective antibody in polyclonal J5 antiserum. Thus, the preparation of readily available crossprotective hyperimmune immunoglobulins is hampered because there is presently no method of selecting appropriate donors or high-titered plasma pools.

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Enhanced survival in Pseudomonas aeruginosa septicemia associated with high levels of circulating antibody to Escherichia coli endotoxin core.

Cited by 102 publications

References 27 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

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

Controversies in the Use of Passive Immunotherapy for Bacterial Infections in the Critically Ill Patient

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