Frazer Institute, The University of Queensland, Brisbane, QLD, Australia.
Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
Front Cell Infect Microbiol. 2024 Aug 13;14:1426773. doi: 10.3389/fcimb.2024.1426773. eCollection 2024.
The complex encompasses a group of gram-negative opportunistic pathogens that cause chronic lung infections in people with cystic fibrosis. Distinct from other respiratory pathogens, causes a unique clinical disease in a subset of patients known as 'cepacia syndrome', fulminant pneumonia accompanied by bacteraemia and sepsis with a mortality rate of up to 75%. Due to the bacteraemia associated with this disease, the mechanisms that allow to resist the bactericidal effects of serum complement-depending killing are vital. Antibodies usually promote serum killing; however, we have described 'cloaking antibodies', specific for lipopolysaccharides that paradoxically protect serum-sensitive bacteria from complement-mediated lysis. Cloaking antibodies that protect have been found in 24%-41% of patients with chronic lung diseases. The presence of these antibodies is also associated with worse clinical outcomes. Here, we sought to determine the relevance of cloaking antibodies in patients with infection.
Twelve spp. were isolated from nine pwCF and characterised for susceptibility to healthy control serum. Patient serum was analysed for the titre of the cloaking antibody. The ability of the patient serum to prevent healthy control serum (HCS) killing of its cognate isolates was determined.
We found that several of the strains were shared between patients. Ten of the 12 isolates were highly susceptible to HCS killing. Four of nine (44%) patients had cloaking antibodies that protected their cognate strain from serum killing. Depleting cloaking antibodies from patient serum restored HCS killing of isolates.
Cloaking antibodies are prevalent in patients with pulmonary infection and protect these strains from serum killing. Removal of cloaking antibodies via plasmapheresis, as previously described for individuals with life-threatening infection, may be a useful new strategy for those with serious and life-threatening infection.
该复合体包括一组革兰氏阴性机会性病原体，这些病原体可导致囊性纤维化患者的慢性肺部感染。与其他呼吸道病原体不同，在一组被称为“洋葱伯克霍尔德菌综合征”的患者中引起独特的临床疾病，暴发性肺炎伴有菌血症和败血症，死亡率高达 75%。由于该疾病与菌血症有关，因此允许 抵抗血清补体依赖性杀伤的杀菌作用的机制至关重要。抗体通常促进血清杀伤；然而，我们已经描述了“伪装抗体”，它们针对脂多糖具有特异性，这与从补体介导的溶解中保护血清敏感细菌的作用相反。在患有慢性肺部疾病的患者中，发现了 24%-41%的具有保护作用的 。这些抗体的存在也与更差的临床结果相关。在这里，我们试图确定 感染患者中伪装抗体的相关性。
从 9 名 pwCF 中分离出 12 株 spp. 并对其对健康对照血清的敏感性进行了特征分析。分析了患者血清中伪装抗体的滴度。测定了患者血清阻止健康对照血清（HCS）杀死其同源分离株的能力。
我们发现，一些 菌株在患者之间共享。12 个分离株中有 10 个对 HCS 杀伤高度敏感。9 名患者中有 4 名（44%）有伪装抗体，可以保护其同源株免受血清杀伤。从患者血清中去除伪装抗体可恢复 HCS 对 分离株的杀伤。
伪装抗体在患有 肺部感染的患者中很常见，并保护这些菌株免受血清杀伤。如前所述，通过血浆置换去除危及生命的 感染个体中的伪装抗体可能是严重和危及生命的 感染患者的一种有用的新策略。
