Carvalho Jairo Campos, Pascoal-Xavier Marcelo Antônio, Araújo Marcelo Grossi, Martins Júlia Pereira, Teixeira-Carvalho Andrea, Gomes Matheus de Souza, Amaral Laurence Rodrigues, Peruhype-Magalhães Vanessa, Coelho-Dos-Reis Jordana Grazziela Alves, Martins-Filho Olindo Assis, Araújo Márcio Sobreira Silva
Instituto René Rachou/FIOCRUZ, Grupo Integrado de Pesquisas em Biomarcadores, Belo Horizonte, Minas Gerais, Brazil.
Fundação Hospitalar do Estado de Minas Gerais (FHEMIG), Belo Horizonte, Minas Gerais, Brazil.
Front Immunol. 2025 Mar 5;16:1513060. doi: 10.3389/fimmu.2025.1513060. eCollection 2025.
The present study aimed to evaluate the performance of plasma immune mediators in classifying leprosy patients [L(PB) and L(MB), paucibacillary and multibacillary leprosy, respectively], leprosy reaction patients (T1LR and T2LR, type 1 and type 2 leprosy reaction, respectively), household contacts (HHC), and non-infected (NI) controls. Quantitative measurements of these immune mediators were carried out using high-throughput multiplex microbead array. The results demonstrated that most of the plasma immune mediators were increased in all clinical groups compared with NI controls. Higher frequencies but lower maximum magnitudes of increase (fold change according to NI) were observed for T1LR (63%, 6.1×) and T2LR (63%, 9.7×) compared with HHC (48%, 68.5×), L(PB) (56%, 8.5×), and L(MB) (48%, 37.9×). The bi-dimensional scattering profiles (magnitude order . significance) identified a higher number of immune mediators in T2LR (12/27) compared with HHC (8/27), L(PB) (7/27), L(MB) (5/27), and T1LR (5/27). CXCL8 was selected as the parameter with the highest accuracy and significance [area under the receiver operating characteristic curve (AUC) = 0.98, = 0.0002] in classifying NI . HHC. CCL3 (C-C motif chemokine ligand 3) was the single analyte with moderate accuracy and significance (AUC = 0.74, = 0.0422) in classifying L(PB) L(MB). IL-9 was selected as an attribute with moderate accuracy and significance (AUC = 0.77, = 0.0041) in classifying T1LR T2LR. Decision tree algorithms confirmed the high accuracy (96%) of CXCL8 in classifying NI . HHC. The use of CCL3 followed by IFN-γ classified L(MB) L(PB) with high accuracy (93%). Moreover, the analysis of IL-9 followed by IL-6 and CXCL10 classified T1RL T2RL with high accuracy (96%). In general, combined stepwise algorithms showed enhanced classification accuracy compared with single-attribute analysis. Together, our findings supported the potential use of plasma immune mediators as complementary laboratory biomarkers for the identification of HHC and the classification of distinct clinical forms of leprosy and leprosy reactions.
本研究旨在评估血浆免疫介质在麻风病患者[分别为L（PB）和L（MB），即少菌型和多菌型麻风病]、麻风反应患者（分别为T1LR和T2LR，即1型和2型麻风反应）、家庭接触者（HHC）以及未感染（NI）对照人群分类中的表现。使用高通量多重微珠阵列对这些免疫介质进行定量测量。结果表明，与NI对照相比，所有临床组中的大多数血浆免疫介质均有所增加。与HHC（48%，68.5倍）、L（PB）（56%，8.5倍）和L（MB）（48%，37.9倍）相比，T1LR（63%，6.1倍）和T2LR（63%，9.7倍）观察到更高的频率但更低的最大增加幅度（相对于NI的倍数变化）。二维散射图谱（幅度顺序. 显著性）显示，与HHC（8/27）、L（PB）（7/27）、L（MB）（5/27）和T1LR（5/27）相比T2LR中鉴定出更多的免疫介质（12/27）。在区分NI和HHC时，CXCL8被选为具有最高准确性和显著性的参数[受试者工作特征曲线下面积（AUC）=0.98，P = 0.0002]。在区分L（PB）和L（MB）时，CCL3（C-C基序趋化因子配体3）是具有中等准确性和显著性的单一分析物（AUC = 0.74，P = 0.0422）。在区分T1LR和T2LR时，IL-9被选为具有中等准确性和显著性的属性（AUC = 0.77，P = 0.0041）。决策树算法证实CXCL8在区分NI和HHC时具有很高的准确性（96%）。使用CCL3后接IFN-γ对L（MB）和L（PB）进行分类具有很高的准确性（93%）。此外，对IL-9后接IL-6和CXCL10进行分析对T1RL和T2RL进行分类具有很高的准确性（96%）。总体而言，与单属性分析相比，组合逐步算法显示出更高的分类准确性。总之，我们的研究结果支持血浆免疫介质作为补充实验室生物标志物用于识别HHC以及区分麻风病和麻风反应不同临床类型的潜在用途。
