Hernández-Bello Jorge, Bach Horacio, Cerpa-Cruz Sergio, Sánchez-Zuno Gabriela Athziri, Hernández-Gutiérrez Rodolfo, Nicoletti Ferdinando, Saraceno Andrea, Muñoz-Valle José
Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud Universidad de Guadalajara, Guadalajara, Mexico.
Division of Infectious Diseases, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada.
PLoS One. 2025 Jan 3;20(1):e0316727. doi: 10.1371/journal.pone.0316727. eCollection 2025.
Studies have noted the connection between Mycobacterium avium subspecies paratuberculosis (MAP) and autoimmunity. MAP is an intracellular pathogen that infects and multiplies in macrophages. To overcome the hostile environment elicited by the macrophage, MAP secretes a battery of virulence factors to neutralize the toxic effects of the macrophage. One of the virulence factors is the Protein Tyrosine Phosphatase A (PtpA), a protein secreted by MAP that interferes in the phago-lysosome fusion, rendering the pathogen unnoticed in the cytoplasm of the macrophage. This study aimed to assess the presence of PtpA antibodies in the sera of Mexican individuals with rheumatoid arthritis (RA) and investigate its possible use as a biomarker for disease activity. We compared RA patients (n = 100) to control subjects (CS) (n = 100) by assessing specific immune responses to PtpA (the antigen) by an indirect ELISA method. Results showed a significant difference in PtpA levels between RA and CS, with RA patients having a median OD of 0.4645 compared to 0.1372 in CS. Antibodies against PtpA were present in 95% of RA patients and 16% of CS (AUC = 0.9163, p = 0.0001). Male control subjects showed higher PtpA reactivity than female CS. The Disease Activity Score (DAS-28) analysis showed that individuals with moderate to high disease activity had lower levels of PtpA reactivity. The results suggest a potential connection between RA and MAP infection.
研究已经注意到副结核分枝杆菌（MAP）与自身免疫之间的联系。MAP是一种细胞内病原体，可在巨噬细胞中感染并繁殖。为了克服巨噬细胞引发的不利环境，MAP分泌一系列毒力因子来中和巨噬细胞的毒性作用。其中一种毒力因子是蛋白酪氨酸磷酸酶A（PtpA），它是由MAP分泌的一种蛋白质，可干扰吞噬溶酶体融合，使病原体在巨噬细胞的细胞质中不被察觉。本研究旨在评估墨西哥类风湿性关节炎（RA）患者血清中PtpA抗体的存在情况，并研究其作为疾病活动生物标志物的潜在用途。我们通过间接ELISA方法评估对PtpA（抗原）的特异性免疫反应，将RA患者（n = 100）与对照受试者（CS）（n = 100）进行比较。结果显示，RA和CS之间的PtpA水平存在显著差异，RA患者的中位OD值为0.4645，而CS为0.1372。95%的RA患者和16%的CS中存在抗PtpA抗体（AUC = 0.9163，p = 0.0001）。男性对照受试者显示出比女性CS更高的PtpA反应性。疾病活动评分（DAS-28）分析表明，中度至高度疾病活动的个体PtpA反应性水平较低。结果表明RA与MAP感染之间可能存在联系。
