IV Immunoglobulin for Acute Lung Injury and Bacteremia in Pseudomonas aeruginosa Pneumonia*

Katoh, Hideya; Yanagimoto, Hiroaki; Shimizu, Masaru; Hamaoka, Saeko; Kinoshita, Mao; Akiyama, Koichi; Sawa, Teiji

doi:10.1097/ccm.0000000000001271

Cited by 27 publications

(36 citation statements)

References 60 publications

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“…This IgG dose was selected on the basis of the results from our previous animal studies, where we reported on the dose-dependent effect of commercially available intravenous immunoglobulin solution. 26 The survival rates and body temperatures of the mice were monitored for 24 h after infection (Fig. 1A and B).…”

Section: Resultsmentioning

confidence: 99%

“…These results imply that high titer anti-PcrV serum from individuals is protective against virulent P. aeruginosa, predominantly by PcrV blockade, and that the antibody fraction from such high titer sera can target other surface proteins in this bacterium, thereby enhancing its prophylactic potency, as we have reported previously. 26 Therefore, in addition to the inhibition of type III secretion-associated virulence by PcrV blockade, human IgG that contains specificities to other P. aeruginosa surface antigens might have contributed to the biological effects observed in our animal models.…”

Section: Discussionmentioning

confidence: 99%

“…While intravenous immunoglobulin (IVIG) has been used against infectious diseases with the expectation of opsonization, immune bacteriolysis and neutralization of toxins and viruses, our results suggest that in antibody-dependent cellular cytotoxicity the role of specific antibody fractions against pathogens in IVIG products should be more focused. 26 Recent meta-analysis and systematic reviews have highlighted the requirement for more evidence from large, well-conducted randomized controlled trials. [29][30][31] However, because IVIG products are derived from donor blood, product-by-product (or lot-by-lot) differences in the specific antibody titers in the IVIG should always be taken into account when interpreting the data from clinical trials on IVIG therapy performed in various countries.…”

Section: Discussionmentioning

confidence: 99%

“…26 Additionally, the efficacy of the immunoglobulin solution against a P. aeruginosa clinical isolate was confirmed in leukopenic mice. 27 The above results imply that a certain subset of the blood donor population has efficaciously high anti-PcrV titers in their sera.…”

Section: Introductionmentioning

confidence: 96%

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The prophylactic effects of human IgG derived from sera containing high anti-PcrV titers against pneumonia-causingPseudomonas aeruginosa

Kinoshita

Kato

Yanagimoto

et al. 2016

Human Vaccines & Immunotherapeutics

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The PcrV cap structure of the type III secretory apparatus of Pseudomonas aeruginosa is a vaccine target. Human immunoglobulin G (IgG) molecules extracted from sera containing high or low antiPcrV titers were tested for their effects against P. aeruginosa pneumonia in a mouse model. Among 198 volunteers, we selected the top 10 high anti-PcrV titer sera and the bottom 10 low anti-PcrV titer sera and extracted the IgG fraction from each serum sample. First, we examined the effects of the IgG against virulent P. aeruginosa. A lethal dose of P. aeruginosa premixed with saline, low titer human IgG, high titer human IgG, or rabbit-derived polyclonal anti-PcrV IgG was intratracheally administered into the lungs of mice, and their survival and lung inflammation were evaluated for 24 h. The high anti-PcrV titer human IgG had a prophylactic effect. Next, the prophylactic effects of intravenous administration of extracted and pooled high or low anti-PcrV titer human IgG were examined. Here, prophylactic intravenous administration of pooled high anti-PcrV titer human IgG, which showed binding capacity to P. aeruginosa PcrV, was more effective than the administration of its low titer pooled equivalent, and the measured physiological and inflammatory parameters correlated with the anti-PcrV titer levels. This result indirectly implies that high anti-PcrV titers in blood can help to protect against virulent P. aeruginosa infections. In addition, the IgG fractions from such high titer sera have potential to be a source of specific intravenous immunoglobulin products for passive vaccination against virulent P. aeruginosa infections.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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The prophylactic effects of human IgG derived from sera containing high anti-PcrV titers against pneumonia-causingPseudomonas aeruginosa

Kinoshita

Kato

Yanagimoto

et al. 2016

Human Vaccines & Immunotherapeutics

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show abstract

“…Previous studies looking at directed antibodies have shown a decrease in airway inflammation and the potential to reduce the prevalence of pneumonia in patients already colonized with P. aeruginosa. In this issue of Critical Care Medicine, Katoh et al (11) examine the utility of IVIG in reducing inflammation, lung injury, and mortality in a mouse model of P. aeruginosa pneumonia. They compared IVIG to a directed antibody and a placebo and showed a reduction in lung injury in their animal model when administered prophylactically.…”

mentioning

confidence: 97%