Nayak Abhijeet, Baarsma M E, van Eck Jacqueline A, Randall Arlo Z, Ursinus Jeanine, Teng Andy A, Pablo Jozelyn V, Hung Chris, Wopereis Doris U M, van de Schoor Freek, Popa Calin D, van den Wijngaard Cees C, Kullberg Bart-Jan, Joosten Leo A B, Kuiper Herman, Campo Joseph J, Liang Xiaouw, Hovius Joppe W
Amsterdam UMC, University of Amsterdam, Center for Infection and Molecular Medicine, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, University of Amsterdam, Amsterdam, the Netherlands.
Amsterdam UMC, University of Amsterdam, Center for Infection and Molecular Medicine, Amsterdam, the Netherlands; Amsterdam Institute for Immunology and Infectious Diseases, University of Amsterdam, Amsterdam, the Netherlands.
Cell Rep Med. 2025 May 20;6(5):102097. doi: 10.1016/j.xcrm.2025.102097. Epub 2025 May 1.
Lyme disease serodiagnosis has limited early sensitivity and cannot distinguish active from past infections. To address this, we screen a Borrelia afzelii whole-proteome microarray (1,296 proteins) using human (n = 149) and murine (n = 32) sera. We evaluate three early-stage antigens-BafPKo_A0001, BafPKo_D0016, and BafPKo_A0029. ELISA cutoffs are established using discovery cohort sera (n = 99) and validated with the validation (n = 242) and the prospective (n = 223) cohorts. A0001 demonstrates 87.8% sensitivity, outperforming C6 (69.4%) and STTT (22.5%) in the discovery cohort. In the validation cohort, A0001 reaches 90.5% sensitivity, surpassing C6 by 11.6% and STTT by 50%. In hyper-acute erythema migrans sera (from the prospective cohort), A0001 achieves 55.1% sensitivity, exceeding C6 and STTT by 14.6% and 33.3%, respectively. COMBO-3 and COMBO-2 yield the highest sensitivity of 92.9% and 66.1% in the validation and prospective cohort, respectively. A0001 and D0016 show enhanced and robust seroreversion after antibiotic treatment suggesting their potential as test of cure biomarkers in early Lyme disease.
莱姆病血清学诊断的早期敏感性有限，无法区分现症感染和既往感染。为解决这一问题，我们使用人（n = 149）和小鼠（n = 32）血清筛选了伯氏疏螺旋体阿费利亚种全蛋白质组微阵列（1296种蛋白质）。我们评估了三种早期抗原——BafPKo_A0001、BafPKo_D0016和BafPKo_A0029。使用发现队列血清（n = 99）建立酶联免疫吸附测定（ELISA）临界值，并在验证队列（n = 242）和前瞻性队列（n = 223）中进行验证。在发现队列中，A0001的敏感性为87.8%，优于C6（69.4%）和STTT（22.5%）。在验证队列中，A0001的敏感性达到90.5%，比C6高11.6%，比STTT高50%。在超急性游走性红斑血清（来自前瞻性队列）中，A0001的敏感性达到55.1%，分别比C6和STTT高14.6%和33.3%。COMBO - 3和COMBO - 2在验证队列和前瞻性队列中的敏感性分别最高，为92.9%和66.1%。A0001和D0016在抗生素治疗后显示出增强且稳定的血清学逆转，表明它们有可能作为早期莱姆病治疗检测生物标志物。
