Naturally occurring antibodies are abundant in human plasma, but their importance in the defence against bacterial pathogens is unclear. We studied the role of the most abundant of such antibodies, the antibody against terminal galactose‐α‐1,3‐galactose (anti‐αGal), in the protection against pneumococcal infections (Streptococcus pneumonia). All known pneumococcal capsular polysaccharides lack terminal galactose‐α‐1,3‐galactose, yet highly purified human anti‐αGal antibody of the IgG class reacted with 48 of 91 pneumococcal serotypes. Anti‐αGal was found to contain multiple antibody subsets that possess distinct specificities beyond their general reactivity with terminal galactose‐α‐1,3‐galactose. These subsets in concert targeted a wide range of microbial polysaccharides. We found that anti‐αGal constituted up to 40% of the total antibody reactivity to pneumococci in normal human plasma, that anti‐αGal drives phagocytosis of pneumococci by human neutrophils and that the anti‐αGal level was twofold lower in patients prone to pneumococcal infections compared with controls. Moreover, during a 48‐year period in Denmark, the 48 anti‐αGal‐reactive serotypes caused fewer invasive pneumococcal infections (n = 10 927) than the 43 non‐reactive serotypes (n = 18 107), supporting protection on the population level. Our findings explain the broad‐spectrum pathogen reactivity of anti‐αGal and support that these naturally occurring polyreactive antibodies contribute significantly to human protective immunity.

中文翻译：

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人类天然抗 αGal 抗体通过广谱多反应性靶向常见病原体

天然存在的抗体在人血浆中含量丰富，但它们在防御细菌病原体中的重要性尚不清楚。我们研究了此类抗体中最丰富的抗体，即末端半乳糖-α -1,3-半乳糖抗体（抗-αGal）在预防肺炎球菌感染（肺炎链球菌）中的作用。所有已知的肺炎球菌荚膜多糖都缺乏末端半乳糖-α -1,3-半乳糖，但高度纯化的 IgG 类人抗 αGal 抗体可与 91 种肺炎球菌血清型中的 48 种发生反应。发现抗-αGal 包含多个抗体亚群，这些抗体亚群具有不同的特异性，超出了它们与末端半乳糖-α的一般反应性。‐1,3-半乳糖。这些子集共同针对广泛的微生物多糖。我们发现，在正常人血浆中，抗 αGal 占对肺炎球菌的总抗体反应性的 40%，抗 αGal 驱动人中性粒细胞对肺炎球菌的吞噬作用，而易患肺炎球菌感染的患者的抗 αGal 水平低两倍与对照相比。此外，在丹麦的 48 年期间，48 种抗 αGal 反应性血清型引起的侵袭性肺炎球菌感染（n  = 10 927）比 43 种非反应性血清型（n = 18 107)，支持人口层面的保护。我们的研究结果解释了抗 αGal 的广谱病原体反应性，并支持这些天然存在的多反应性抗体对人类保护性免疫有显着贡献。