High levels of antibody to panton-valentine leukocidin are not associated with resistance to Staphylococcus aureus-associated skin and soft-tissue infection.

High levels of antibody to panton-valentine leukocidin are not associated with resistance to Staphylococcus aureus-associated skin and soft-tissue infection.
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DOI:
10.1086/656742
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发表时间:
2010-11-15
期刊:
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子:
--
通讯作者:
Pier GB
Pier GB
中科院分区:
其他
文献类型:
--
作者:
Hermos CR;Yoong P;Pier GB

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表达Panton-Valentine杀白细胞素(PVL)的社区相关耐甲氧西林金黄色葡萄球菌(CA-MRSA)引起严重的皮肤和软组织感染(SSTI)、坏死性肺炎和其他侵袭性感染。PVL毒素被认为是一种毒力因子,该毒素的一种组分的抗体正在作为候选疫苗进行研究。PVL在发病机制中的作用仍然存在争议,并且不知道人血清抗PVL抗体是否调节感染。我们测定了0 - 18岁儿童血清中PVL的抗体水平,这些儿童表现为PCR证实的PVL阳性MRSA SSTI,有或没有先前的MRSA感染或SSTI,PVL阳性MRSA侵袭性感染,PVL阴性MRSA感染和未感染的对照。我们还测量了抗体介导的PVL诱导的人多形核细胞溶解的中和作用。PVL抗体存在于健康儿童中,在4 - 6岁时达到成人水平,在4 - 6个月时达到最低点,可能是由于母体抗体的丧失。原发性PVL阳性MRSA感染的儿童有中等水平的PVL抗体,在感染后增加。先前有MRSA或SSTI感染的儿童在感染开始时有高水平的PVL抗体。感染后血清PVL抗体水平无明显升高。来自PVL阳性MRSA SSTI儿童的血清,特别是那些先前患有MRSA或SSTI的儿童,以及来自侵袭性PVL阳性MRSA感染儿童的恢复期血清,有效地抑制了PVL诱导的PMN溶解。PVL中和抗体不能保护儿童免受原发性或复发性CA-MRSA SSTI的侵害。
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) expressing Panton-Valentine Leukocidin (PVL) cause severe skin and soft tissue infections (SSTI), necrotizing pneumonia and other invasive infections. PVL toxin has been implicated as a virulence factor and antibody to a component of this toxin is under investigation as a vaccine candidate. The role of PVL in pathogenesis remains controversial and it is unknown if human serum antibody to PVL modulates infection. We determined antibody levels to PVL in sera from children aged 0-18 years presenting with PCR-confirmed PVL-positive MRSA SSTI with or without prior MRSA infection or SSTI, PVL-positive MRSA invasive infections, PVL-negative MRSA infections and uninfected controls. We also measured antibody-mediated neutralization of PVL-induced lysis of human polymorphonuclear cells. Antibody to PVL was present in healthy children reaching adult levels by 4-6 years with a nadir at 4-6 months likely due to loss of maternal antibody. Children with a primary PVL-positive MRSA infection had moderate levels of antibody to PVL that increased following infection. Children with prior MRSA or SSTI infections had high levels of antibody to PVL at the onset of infection. There was no increase in antibody to PVL in this populations’ sera after the onset of infection. Sera from children with PVL-positive MRSA SSTIs, particularly those with prior MRSA or SSTI, and convalescent sera from children with invasive PVL-positive MRSA infection, potently inhibited PVL-induced lysis of PMNs. Neutralizing antibody to PVL does not protect children against primary or recurrent CA-MRSA SSTI.
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