Autoantibodies inhibit Plasmodium falciparum growth and are associated with protection from clinical malaria

IF 25.5 1区 医学 Q1 IMMUNOLOGY Immunity Pub Date : 2024-06-19 DOI:10.1016/j.immuni.2024.05.024
Kelly A. Hagadorn, Mary E. Peterson, Hemanta Kole, Bethany Scott, Jeff Skinner, Ababacar Diouf, Eizo Takashima, Aissata Ongoiba, Safiatou Doumbo, Didier Doumtabe, Shanping Li, Padmapriya Sekar, Mei Yan, Chengsong Zhu, Hikaru Nagaoka, Bernard N. Kanoi, Quan-Zhen Li, Carole Long, Eric O. Long, Kassoum Kayentao, Christine S. Hopp
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Abstract

Many infections, including malaria, are associated with an increase in autoantibodies (AAbs). Prior studies have reported an association between genetic markers of susceptibility to autoimmune disease and resistance to malaria, but the underlying mechanisms are unclear. Here, we performed a longitudinal study of children and adults (n = 602) in Mali and found that high levels of plasma AAbs before the malaria season independently predicted a reduced risk of clinical malaria in children during the ensuing malaria season. Baseline AAb seroprevalence increased with age and asymptomatic Plasmodium falciparum infection. We found that AAbs purified from the plasma of protected individuals inhibit the growth of blood-stage parasites and bind P. falciparum proteins that mediate parasite invasion. Protected individuals had higher plasma immunoglobulin G (IgG) reactivity against 33 of the 123 antigens assessed in an autoantigen microarray. This study provides evidence in support of the hypothesis that a propensity toward autoimmunity offers a survival advantage against malaria.

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自身抗体抑制恶性疟原虫的生长,并与临床疟疾的防护有关
包括疟疾在内的许多感染都与自身抗体(AAbs)的增加有关。之前的研究报告称,自身免疫性疾病易感性的遗传标记与疟疾抵抗力之间存在关联,但其潜在机制尚不清楚。在这里,我们对马里的儿童和成人(n = 602)进行了一项纵向研究,发现疟疾季节前血浆中的高水平 AAbs 可独立预测儿童在随后的疟疾季节中患临床疟疾的风险降低。基线 AAb 血清流行率随年龄和无症状恶性疟原虫感染而增加。我们发现,从受保护者血浆中纯化的 AAb 可抑制血期寄生虫的生长,并与介导寄生虫入侵的恶性疟原虫蛋白结合。在自身抗原微阵列评估的 123 种抗原中,受保护者血浆免疫球蛋白 G (IgG) 对 33 种抗原的反应性更高。这项研究为自身免疫倾向提供了支持性证据,证明了自身免疫倾向能使人在疟疾面前获得生存优势的假设。
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来源期刊
Immunity
Immunity 医学-免疫学
CiteScore
49.40
自引率
2.20%
发文量
205
审稿时长
6 months
期刊介绍: Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.
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